Academic literature on the topic 'Lymphoid progenitors'
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Journal articles on the topic "Lymphoid progenitors"
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Harly, Christelle, Maggie Cam, Jonathan Kaye, and Avinash Bhandoola. "Development and differentiation of early innate lymphoid progenitors." Journal of Experimental Medicine 215, no. 1 (November 28, 2017): 249–62. http://dx.doi.org/10.1084/jem.20170832.
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Early innate lymphoid progenitors (EILPs) have recently been identified in mouse adult bone marrow as a multipotential progenitor population specified toward innate lymphoid cell (ILC) lineages, but their relationship with other described ILC progenitors is still unclear. In this study, we examine the progenitor–successor relationships between EILPs, all-lymphoid progenitors (ALPs), and ILC precursors (ILCps). Functional, bioinformatic, phenotypical, and genetic approaches collectively establish EILPs as an intermediate progenitor between ALPs and ILCps. Our work additionally provides new candidate regulators of ILC development and clearly defines the stage of requirement of transcription factors key for early ILC development.
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Borikar, Sneha, Vivek Philip, Lauren Kuffler, and Jennifer J. Trowbridge. "Lysine Methyltransferase Kmt5a Restricts Myeloid-Biased Output of Lymphoid-Primed Multipotent Progenitors." Blood 128, no. 22 (December 2, 2016): 1487. http://dx.doi.org/10.1182/blood.v128.22.1487.1487.
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Abstract Distinct, lineage-biased subsets of multipotent progenitor cells (MPP) dynamically respond to the demands of the hematopoietic system to replenish mature hematopoietic cells as needed. It currently remains unclear as to whether distinct epigenetic mechanisms regulate lineage-specific expansion and differentiation from MPPs. Focusing on lymphoid-primed multipotent progenitor cells (LMPP/MPP4), we performed a lentiviral shRNA screen of 15 epigenetic factors, selected based on differential expression between myeloid-restricted and lymphoid-restricted progenitors. Following a 48 hour infection with lentiviral shRNA constructs or a non-targeting control, the lineage potential of lymphoid-primed multipotent progenitors was interrogated by myeloid and lymphoid colony forming unit (CFU) assays. From this screen, knockdown of the lysine methyltransferase Kmt5a most dramatically altered lineage output from lymphoid-primed multipotent progenitors through an expansion of myeloid lineage colonies without altering lymphoid colony production. To confirm target specificity, two independent shRNA hairpins targeting distinct locations of the Kmt5a transcript demonstrated that knockdown of Kmt5a (97.1% and 99.5% versus non-targeting control shRNA) increased macrophage colony production by 1.94 and 1.95 fold, respectively (P < 0.01 and P < 0.05, n = 3). Preliminary single cell culture experiments support that the enhanced myeloid lineage output from lymphoid-primed multipotent progenitors occurs at the single-cell level through increased cloning efficiency of myeloid-biased cells. Our results suggest that Kmt5a functions to restrict myeloid lineage output from lymphoid-primed multipotent progenitors. Mechanistically, KMT5A is responsible for monomethylation of histone H4K20 and the methylation of non-histone proteins (ex. p53K376). Our ongoing work aims to distinguish between these histone and non-histone targets to determine the precise mechanisms restricting myeloid lineage output from lymphoid-primed multipotent progenitors. This work has direct implications for a better understanding of the molecular drivers of transient myeloid lineage reprogramming of lymphoid-primed multipotent progenitors during hematopoietic regeneration, age associated myeloid lineage skewing of hematopoiesis, and myeloid malignancies. Disclosures No relevant conflicts of interest to declare.
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Becker, Amy M., Drew G. Michael, Ansuman T. Satpathy, Roger Sciammas, Harinder Singh, and Deepta Bhattacharya. "IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors." Blood 119, no. 9 (March 1, 2012): 2003–12. http://dx.doi.org/10.1182/blood-2011-06-364976.
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Abstract While most blood lineages are assumed to mature through a single cellular and developmental route downstream of HSCs, dendritic cells (DCs) can be derived from both myeloid and lymphoid progenitors in vivo. To determine how distinct progenitors can generate similar downstream lineages, we examined the transcriptional changes that accompany loss of in vivo myeloid potential as common myeloid progenitors differentiate into common DC progenitors (CDPs), and as lymphoid-primed multipotent progenitors (LMPPs) differentiate into all lymphoid progenitors (ALPs). Microarray studies revealed that IFN regulatory factor 8 (IRF-8) expression increased during each of these transitions. Competitive reconstitutions using Irf8−/− BM demonstrated cell-intrinsic defects in the formation of CDPs and all splenic DC subsets. Irf8−/− common myeloid progenitors and, unexpectedly, Irf8−/− ALPs produced more neutrophils in vivo than their wild-type counterparts at the expense of DCs. Retroviral expression of IRF-8 in multiple progenitors led to reduced neutrophil production and increased numbers of DCs, even in the granulocyte-macrophage progenitor (GMP), which does not normally possess conventional DC potential. These data suggest that IRF-8 represses a neutrophil module of development and promotes convergent DC development from multiple lymphoid and myeloid progenitors autonomously of cellular context.
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Karsunky, Holger, Miriam Merad, Antonio Cozzio, Irving L. Weissman, and Markus G. Manz. "Flt3 Ligand Regulates Dendritic Cell Development from Flt3+ Lymphoid and Myeloid-committed Progenitors to Flt3+ Dendritic Cells In Vivo." Journal of Experimental Medicine 198, no. 2 (July 21, 2003): 305–13. http://dx.doi.org/10.1084/jem.20030323.
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Stimulation of Flt3 receptor tyrosine kinase through its cognate ligand expands early hematopoietic progenitor and dendritic cells (DCs) in humans and mice. The exact developmental stages at which hematopoietic progenitors express Flt3, are responsive to its ligand, and subsequently develop to DCs, are not known. Here we show that common lymphoid and common myeloid progenitors, as well as steady state DCs in thymus, spleen, and epidermis, express Flt3. The receptor is down-regulated once definitive B cell, T cell, and megakaryocyte/erythrocyte commitment occurs, and Flt3 is not detectable on other steady state hematopoietic cell populations. Upon in vivo Flt3 ligand (Flt3L) administration, Flt3+ progenitor cells and their progeny DCs are expanded, whereas Flt3− downstream progenitors are not, or are only slightly increased. Transplantation of common lymphoid and common myeloid progenitors and subsequent Flt3L injection increases progeny DCs of both precursor populations. These findings provide a definitive map of Flt3 expression in the hematopoietic hierarchy and directly demonstrate that Flt3L can drive DC development along both the lymphoid and myeloid developmental pathways from Flt3+ progenitors to Flt3+ DCs.
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Buza-Vidas, Natalija, Petter Woll, Anne Hultquist, Sara Duarte, Michael Lutteropp, Tiphaine Bouriez-Jones, Helen Ferry, Sidinh Luc, and Sten Eirik Waelgaard Jacobsen. "FLT3 expression initiates in fully multipotent mouse hematopoietic progenitor cells." Blood 118, no. 6 (August 11, 2011): 1544–48. http://dx.doi.org/10.1182/blood-2010-10-316232.
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Abstract Lymphoid-primed multipotent progenitors with down-regulated megakaryocyte-erythroid (MkE) potential are restricted to cells with high levels of cell-surface FLT3 expression, whereas HSCs and MkE progenitors lack detectable cell-surface FLT3. These findings are compatible with FLT3 cell-surface expression not being detectable in the fully multipotent stem/progenitor cell compartment in mice. If so, this process could be distinct from human hematopoiesis, in which FLT3 already is expressed in multipotent stem/progenitor cells. The expression pattern of Flt3 (mRNA) and FLT3 (protein) in multipotent progenitors is of considerable relevance for mouse models in which prognostically important Flt3 mutations are expressed under control of the endogenous mouse Flt3 promoter. Herein, we demonstrate that mouse Flt3 expression initiates in fully multipotent progenitors because in addition to lymphoid and granulocyte-monocyte progenitors, FLT3− Mk- and E-restricted downstream progenitors are also highly labeled when Flt3-Cre fate mapping is applied.
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Sitnicka, Ewa, Natalija Buza-Vidas, Henrik Ahlenius, Corrado M. Cilio, Christos Gekas, Jens M. Nygren, Robert Månsson, et al. "Critical role of FLT3 ligand in IL-7 receptor–independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors." Blood 110, no. 8 (October 15, 2007): 2955–64. http://dx.doi.org/10.1182/blood-2006-10-054726.
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Abstract The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow (BM) stem/progenitor cells that continuously replace thymic progenitors remain largely unknown. Herein, we show that fms-like tyrosine kinase 3 (Flt3) ligand (Fl)–deficient mice have distinct reductions in the earliest thymic progenitors in fetal, postnatal, and adult thymus. A critical role of FL in thymopoiesis was particularly evident in the absence of interleukin-7 receptor α (IL-7Rα) signaling. Fl−/−Il-7r−/− mice have extensive reductions in fetal and postnatal thymic progenitors that result in a loss of active thymopoiesis in adult mice, demonstrating an indispensable role of FL in IL-7Rα–independent fetal and adult T lymphopoiesis. Moreover, we establish a unique and critical role of FL, distinct from that of IL-7Rα, in regulation of the earliest lineage-negative (Lin−) Lin−SCA1+KIT+ (LSK) FLT3hi lymphoid-primed multipotent progenitors in BM, demonstrating a key role of FLT3 signaling in regulating the very earliest stages of lymphoid progenitors.
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Ryan, Daniel H., Bonnie L. Nuccie, Ion Ritterman, Jane L. Liesveld, Camille N. Abboud, and Richard A. Insel. "Expression of Interleukin-7 Receptor by Lineage-Negative Human Bone Marrow Progenitors With Enhanced Lymphoid Proliferative Potential and B-Lineage Differentiation Capacity." Blood 89, no. 3 (February 1, 1997): 929–40. http://dx.doi.org/10.1182/blood.v89.3.929.
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Abstract Relatively little is known about the relationship of lymphoid-associated gene expression to the proliferation and differentiation potential of early human bone marrow lymphoid progenitors. Surface expression of interleukin-7 (IL-7) receptor-α (IL-7Rα), a component of the high-affinity receptor for the lymphoid precursor growth factor IL-7, defined a CD34+ progenitor subset lacking the CD19+ pro-B phenotype but demonstrating markedly enhanced lymphoid clonogenic capacity and the ability to differentiate into pro-B cells in short-term culture. These progenitors expressed mRNA for the lymphoid-associated genes Igβ, RAG-1, and PAX-5, and were uniformly TdT-positive (TdT+). In contrast, IL-7Rα−/CD19−/CD34+ progenitors had a 50-fold reduced lymphoid clonogenic capacity and did not differentiate into pro-B cells in short-term culture. Expression of TdT and the lymphoid-associated genes Igβ and RAG-1, but not PAX-5, was detected in this fraction, although at lower levels than in the IL-7Rα+ progenitors. In contrast to IL-7Rα, loss of the stem cell factor receptor c-kit was associated with enhanced lymphoid clonogenic potential and increased B-lineage differentiation potential. These results indicate that IL-7Rα expression defines entry into a developmental stage characterized by upregulation of multiple lymphoid-associated genes and enhanced fitness for B-lymphoid differentiation. The onset of IL-7Rα and PAX-5 expression immediately before acquisition of CD19 is consistent with evidence suggesting upregulation of CD19 through pathways involving PAX-5 and IL-7.
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Arinobu, Yojiro, Shin-ichi Mizuno, Hirokazu Shigematsu, Hidetoshi Ozawa, Yong Chong, Hiromi Iwasaki, Philippe Kastner, Susan Chan, and Koichi Akashi. "Delineation of the Common Developmental Pathway for Granulocyte/Monocyte and Lymphoid Lineages by Using an Expression Reporter for PU.1." Blood 108, no. 11 (November 16, 2006): 1656. http://dx.doi.org/10.1182/blood.v108.11.1656.1656.
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Abstract Understanding how multipotent cells commit to each of their terminal fate potentials is an important aspect of stem cell biology. Hematopoietic stem cells (HSCs) of Lin −Sca-1+c-Kit+ (LSK) phenotype have been purified, which were further divided into CD34-long-term and CD34+ short-term (ST)-HSCs. The existence of phenotypically isolatable common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs) downstream of ST-HSCs suggests that the first commitment step after the HSC stage is the bifurcation of lymphoid vs. myeloid pathway. Recent studies, however, suggest that the loss of MegE potential could be an early event in HSC stage. For example, LSK cells activating RAG-1 or Flt-3 expression retained granulocyte/monocyte (GM) but not megakaryocyte/erythrocyte (MegE) potential together with lymphoid potential, suggesting the existence of common progenitor for GM and lymphoid lineages. Here we report that a fraction of ST-LSK cells expressing high levels of PU.1, a transcription factor necessary for GM and lymphoid development, represents GM/lymphoid bipotent progenitors. In mice harboring knock-in GFP reporter for PU.1, LSK cells were divided into GFP high and GFP low subpopulations. Although PU.1low LSK cells were multipotent, PU.1high LSK cells differentiated only into GM and lymphoid cells in vitro and in vivo. We also found that single PU.1high LSK cells differentiated into GM, T and B cells in vivo. These data formally prove the existence of the third major early progenitor population activating PU.1 at a high level, the granulocyte/monocyte/lymphoid progenitor (GMLP). The existence of prospectively isolatable GMLPs strongly suggests that HSCs sequentially lose MegE then GM potential during their lymphoid commitment.
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Katsura, Yoshimoto. "Redefinition of lymphoid progenitors." Nature Reviews Immunology 2, no. 2 (February 2002): 127–32. http://dx.doi.org/10.1038/nri721.
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Loughran, Stephen J., Federico Comoglio, Fiona K. Hamey, Alice Giustacchini, Youssef Errami, Eleanor Earp, Berthold Göttgens, et al. "Mbd3/NuRD controls lymphoid cell fate and inhibits tumorigenesis by repressing a B cell transcriptional program." Journal of Experimental Medicine 214, no. 10 (September 12, 2017): 3085–104. http://dx.doi.org/10.1084/jem.20161827.
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Differentiation of lineage-committed cells from multipotent progenitors requires the establishment of accessible chromatin at lineage-specific transcriptional enhancers and promoters, which is mediated by pioneer transcription factors that recruit activating chromatin remodeling complexes. Here we show that the Mbd3/nucleosome remodeling and deacetylation (NuRD) chromatin remodeling complex opposes this transcriptional pioneering during B cell programming of multipotent lymphoid progenitors by restricting chromatin accessibility at B cell enhancers and promoters. Mbd3/NuRD-deficient lymphoid progenitors therefore prematurely activate a B cell transcriptional program and are biased toward overproduction of pro–B cells at the expense of T cell progenitors. The striking reduction in early thymic T cell progenitors results in compensatory hyperproliferation of immature thymocytes and development of T cell lymphoma. Our results reveal that Mbd3/NuRD can regulate multilineage differentiation by constraining the activation of dormant lineage-specific enhancers and promoters. In this way, Mbd3/NuRD protects the multipotency of lymphoid progenitors, preventing B cell–programming transcription factors from prematurely enacting lineage commitment. Mbd3/NuRD therefore controls the fate of lymphoid progenitors, ensuring appropriate production of lineage-committed progeny and suppressing tumor formation.
Dissertations / Theses on the topic "Lymphoid progenitors"
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Zandi, Sasan. "What’s in a name? : Sub-fractionation of common lymphoid progenitors." Doctoral thesis, Linköpings universitet, Experimentell hematologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-61590.
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The hematopoietic system is a highly dynamic organ developed in many multi-cellular organisms to provide oxygen, prevent bleeding and to protect against microorganisms. The blood consist of many different specialized cells that all derive from rare hematopoietic stem cells (HSCs) located in the bone marrow in mice and humans. Blood cell production from HSCs occurs in a stepwise manner through development of intermediate progenitors that gradually loose lineage potentials. This is a tightly regulated process with complex regulatory mechanisms and many checkpoints that ensure a high and balanced production of blood cells. One of the fundamental questions in hematopoiesis relates to how the maturation of the cells is controlled and driven towards defined cell fates. The understanding of these processes is largely facilitated by isolation of intermediate populations of cells at defined stages of development. This thesis is focused on the regulatory mechanisms that regulate the maturation of B-lymphocytes constituting an important part of adaptive immunity by being responsible for the production of antibodies. It has been suggested that all the lymphoid cells have a common lineage restricted ancestor defined as a Lin-KitloSca1loFlt3+IL7R+ common lymphoid progenitor (CLP). These cells are believed retain the combined potentials for B, T and NK cells and it has been presumed that commitment of CLPs to B lineage is associated with expression of CD19 and B220 on progenitor B-cells. The aim of this thesis has been to identify the point of no return in B-cell development in order to allow for a better understanding of lineage restriction events in early lymphopoesis. To this end, we have used reporter transgenic mice where marker gene expression has been controlled by the transcription regulatory elements from one early lymphoid marker (Rag1) and one B-lymphoid restricted gene (λ5, Igll1). This allowed us to identify three functionally distinct sub-populations within the conventional CLP compartment. The cells were identified as CLPRaglowλ5- cells retaining B, T, Nk and a limited myeloid potential while up-regulation of Rag1 to generate CLPRaghighλ5- cells, was associated with loss of Nk potential as well as of the residual myeloid potential. Ultimately expression of λ5 in the CLPRag1highλ5+ compartment identifies the first committed B cells. Hence, our data suggest that the point of no return in B-cell development can be found within the CD19- CLP compartment. Using this new model for B-cell development, we investigated the instructive vs. permissive role of IL7 signaling in B cell commitment. Our results show that in absence of IL7, CLP maturation is impaired and generation of the earliest committed B-lineage cells is severely impaired. CLP maturation could not be rescued by ectopic expression of the anti-apoptotic Bcl2 protein even though the cells were able to generate normal B lineage cells after restoration of the IL7 signal. These findings suggest that Il7 is crucial for the maturation of lineage restricted CLPs and provide support for an instructive role of IL7 in early Bcell development. This thesis highlights the importance of precise identification of the point of commitment in B cell development and provides insight to the hematopoietic hierarchical model with the potential to serve as a map to better understand the mechanisms of hematopoietic disorders.
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Lemoine, François Michel. "Studies of the interactions between stromal cells and B lymphoid progenitors." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/28856.
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The overall goal of the work, described in this thesis was to investigate the molecular mechanisms that regulate normal pre-B cell proliferation and how these may be altered in transformed pre-B cells. Monoclonal antibodies and molecular biological techniques have allowed a number of stages of pre-B cell differentiation to be defined but little is known about mechanisms controlling their proliferation.
Studies of pre-B cell production in animal models and in long-term cultures that support pre-B cell proliferation have suggested that stromal cells play a key role in this regard. As a first step to investigate the mechanisms involved, a number of pre-B cell supportive murine stromal cell lines were isolated and characterized. A number of pre-B cell lines were also isolated, cloned and characterized. From these, spontaneous and Abelson murine leukemia virus transformants were derived. These cell lines were then used in co-culture experiments to demonstrate that stromal cells constitutively secrete a pre-B stimulating factor. Characterization of the pre-B cell stimulating activity produced by one stromal cell line (M2-10B4) showed it to be a 10 Kd molecule sensitive to freezing and different from any cloned hemopoietic growth factor described to date. The possibility that extracellular matrix components might be involved in stromal cell-mediated control of pre-B cell growth was also investigated. It was found that pre-B cells attach specifically to fibronectin and that although fibronectin by itself cannot support pre-B cell proliferation, it contributes to stromal cell stimulation of pre-B cell growth.
Both of these mechanisms were found to be affected in malignantly transformed pre-B cell populations irrespective of the mode of transformation. Transformed pre-B cells were found to have acquired the ability to secrete a novel 3 Kd autocrine factor that is also capable of stimulating normal pre-B cells. In addition transformed pre-B cells showed a greatly decreased ability to adhere to fibronectin and had become insensitive to the synergistic stimulating effect of fibronectin. It will be of interest to determine in the future whether these findings have a counterpart in human malignant pre-B cell populations.Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate
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Rondeau, Vincent. "Rôle de la désensibilisation de CXCR4 dans la spécification lympho-myéloïde des progéniteurs hématopoïétiques multipotents. Lymphoid differentiation of hematopoietic stem cells requires efficient Cxcr4 desensitization New method to obtain lymphoid progenitors CXCR4-driven mitochondrial metabolic pathways shape the lympho-myeloid fate of hematopoietic multipotent progenitors." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASQ022.
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Les cellules souches et progéniteurs hématopoïétiques (CSPHs), incluant les progéniteurs multipotents (MPPs), sont responsables de la production des cellules immunes circulantes. Ils résident dans la moelle osseuse (MO) au sein de structures spécialisées, les niches endostéale et (péri)-vasculaire, qui régulent la spécification et l'engagement lymphoïde versus myéloïde des CSPHs. Dans la MO, le couple formé par la chimiokine CXCL12 et l’un de ses récepteurs, CXCR4, exerce un rôle clé dans la régulation de la rétention et la quiescence des CSPHs. Ces processus sont dérégulés dans le Syndrome WHIM (SW), une maladie immuno-hématologique rare liée à des mutations autosomiques dominantes du gène codant CXCR4, qui altèrent la désensibilisation du récepteur et conduisent à un gain de fonction en réponse à CXCL12. Cliniquement, le SW se caractérise notamment par une profonde leucopénie circulante qui affecte les lignages lymphoïde et myéloïde et dont les mécanismes restent à déterminer. Grâce à un modèle murin génétiquement modifié du SW et à l'accès à des prélèvements biologiques de patients atteints du SW, nous avons testé l'hypothèse que la lymphopénie circulante associée au SW résultait de défauts hématopoïétiques dans la MO. Nous avons révélé un rôle clé de la désensibilisation de CXCR4 dans la différenciation lymphoïde des CSPHs et identifié les MPPs comme étant le stade défectueux dans le SW. La divergence entre les lignages lymphoïde et myeloïde se produit précisément à ce stade au sein duquel règne une hétérogénéité : les MPP2/3 sont biaisés myéloïde et les MPP4 sont orientés lymphoïde. Notre compréhension de la façon dont les signaux extrinsèques (niches) et intrinsèques aux MPPs déterminent leur devenir lymphoïde versus myéloïde est encore parcellaire. Dans ce contexte, l’objectif de ma thèse a été de déterminer si et comment la signalisation de CXCR4 régule la dépendance énergétique des MPPs et à comprendre comment les voies métaboliques façonnent leur spécification lympho-myéloïde. Dans la MO des souris porteuses de la mutation gain de fonction de Cxcr4, nous avons observé une diminution du nombre de MPP4 qui contrastait avec l'augmentation des MPP2/3. L’analyse de prélèvements médullaires de patients a également permis de rapporter une diminution de la fréquence des progéniteurs lymphoïdes et une augmentation de celle des progéniteurs myéloïdes. Chez la souris mutantes, ce biais myéloïde du compartiment de MPPs s'avèrait associé à une expansion anormale et une reprogrammation moléculaire et métabolique des MPP4. Fait marquant, un traitement chronique par l’AMD3100, un antagoniste de CXCR4, permettait de normaliser le nombre de MPP4 dans la MO, de restaurer leurs propriétés métaboliques, et de corriger la lymphopénie des souris mutantes. Par conséquent, nos résultats suggèrent que l’axe CXCL12/CXCR4 est requis au maintien du potentiel lymphoïde des MPP4 au travers de la modulation de leur activité métabolique mitochondrialeHematopoietic stem and progenitor cells (HSPCs), including the multipotent progenitors (MPPs), are responsible for replenishing immune cells. They reside in bone marrow (BM) endosteal and (peri)-vascular niches, which provide all cellular and molecular components required for their lifelong maintenance and fate. Among them, the CXCL12 chemokine and one of its receptor, CXCR4, exert a dominant role in promoting HSPC retention and quiescence. These processes are deregulated in the WHIM Syndrome (WS), a rare immunodeficiency caused by inherited heterozygous autosomal gain-of-function CXCR4 mutations that affect homologous desensitization of the receptor. Clinically, WS is notably characterized by severe, chronic circulating lymphopenia whose mechanisms remain to be elucidated. Using a mouse model carrying a naturally occurring WS-linked Cxcr4 mutation as well as human BM and blood samples, we explored the possibility that the lymphopenia in WS originates from defects at the HSPC level in BM. We reported that Cxcr4 desensitization is required for lymphoid differentiation of HSPCs and further identified the MPP stage as defective in mutant mice. The divergence between lymphoid and myeloid lineages occurs at the MPP stage, which is composed of distinct subpopulations, i.e., MPP2 and MPP3 are reported as distinct myeloid-biased MPP subsets that operate together with lymphoid-primed MPP4 to control blood leukocyte production. Our understanding of how cell-extrinsic niche-related and cell-intrinsic cues drive the lymphoid versus myeloid fate decision of MPPs is still fragmentary. Therefore, my PhD project aimed at determining whether and how CXCR4 signaling regulates bioenergetics demands of MPPs and at understanding how these metabolic pathways shape the lympho-myeloid fate of MPPs. We unraveled a myeloid skewing of the HSPC compartment in BM of WS mice and patients. In mutant mice, this partly relied on the contraction of the MPP4 pool and on cell-autonomous molecular and metabolic changes that reprogramed MPP4 away from lymphoid differentiation. Interestingly, chronic treatment with the CXCR4 antagonist AMD3100 normalized mitochondrial metabolism and fate of MPP4, while correcting circulating lymphopenia in WS mice. This study provides evidence that CXCR4 signaling acts as an essential gatekeeper for integrity of the mitochondrial machinery, which in turn controls lymphoid potential of MPP4
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Reimann, Christian. "In-vitro Generation of potent T-lymphoid Progenitors in a feeder-cell-free DL-4 system." Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00771452.
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Human leukocyte antigen (HLA)-mismatched haematopoietic stem cell transplantation (HSCT) represents an important therapeutic option for patients lacking suitable donors. Delayed posttransplant immune recovery constitutes one of its major complications and is most pronounced in the T cellular compartment. A novel strategy to promote de novo thymopoiesis from donor derived HSCs and to accelerate T cellular reconstitution in patients after HSCT consists in the adoptive transfer of in vitro generated T cell progenitor cells. Identification of Notch1 as the key regulator of early T-lineage development has allowed the generation of Notch ligand-based culture systems, which provide a powerful tool to generate T-lymphoid progenitors in vitro. The efficacy of murine T-lymphoid progenitors to promote T cell reconstitution has been well demonstrated in conventional mouse models. In consistency, in vitro-generated human T cell progenitors were demonstrated to promote thymic recovery in humanized mice. Yet, positive effects of in vitro generated human T cell precursors on peripheral T cell reconstitution have not been demonstrated. Moreover currently used Notch-based co-culture systems consist of genetically modified murine cell lines. With view to establishing a clinically applicable system, feeder-cell-free Notch-ligand culture systems for the generation of T-lymphopoietic progenitors are warranted. During my PhD project I developed a new culture system based on the immobilized Notch ligand Delta-like-4 (DL-4). Exposure of human CD34+ cord blood cells to immobilized DL-4 enabled the in vitro generation of high number of T cell progenitors, which harboured the phenotype of immature early thymic progenitor cells (ETP) and prothymocytes (proT). ETP and proT cell generated during DL-4 culture upregulated essential genes involved in early T-lymphoid development (i.e. IL7Rα, PTα, RAG1 and BCL11b) and had undergone stage-specific recombination of the T cell receptor (TCR) locus in a similar way as in native human thymopoiesis. In limiting dilution analysis after secondary OP9/DL-1 co-culture, DL-4 progenitors displayed a highly increased T-lymphoid potential, which could be entirely attributed to the ETP and proT subset. When transferred into NOD/SCID/γc-/- mice, DL-4 primed T cell progenitors migrated to the thymus and accelerated intrathymic T cell differentiation and emergence of functional, mature and polyclonal αβ T cells in the periphery. In a co-transplantation approach, which more closely mimics a clinical setting, DL-4 progenitors and untreated CD34+ cells from HLA-disparate donors were simultaneously injected in the same recipient. This procedure allowed even more rapid and more robust T cell reconstitution. HLA-tracking of the distinct graft sources further showed, that DL-4 progenitors specifically reconstituted the T-lymphoid compartments. This work provides further evidence for the ability of in vitro-generated human T cell progenitors to promote de novo thymopoiesis and shows for the first time, that these cells accelerate peripheral T cell reconstitution in humanized mice. The availability of the efficient feeder-cell-free DL-4 culture technique represents an important step towards the future clinical exploitation translation of in vitro generated T-lymphoid progenitor cells to improve posttransplant immune reconstitution
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Moreira, Pedro Miguel Lopes. "Role of Notch signaling on the differentiation of early lymphoid progenitors cells: a view throughout the development of the embryonic chicken thymus and spleen." Master's thesis, Faculdade de Ciências e Tecnologia, 2014. http://hdl.handle.net/10362/13012.
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Dissertação para a obtenção do grau de Mestre em Genética Molecular e BiomedicinaThe lymphoid organs, thymus and spleen, are essential for the differentiation of T and B cells, respectively. One of the signaling pathways involved in processes of cell differentiation is the Notch signaling pathway. Work conducted by our group demonstrated that Notch ligands, receptors and target genes are expressed in the thymic epithelium. In this work, we aimed: 1) to study the organogenesis of the thymus and spleen in chicken embryos; 2) phenotypically characterize the cells present in both organs; 3) to study the role of Notch signaling in the differentiation of hematopoietic progenitors (PH) isolated from thymus and spleen of the chicken embryo. To study the formation of the thymus and spleen and characterize the cell populations present within them during embryonic development, we stained histological sections of the organs and citospins with Hematoxylin-Eosin (HE). To elucidate the role of Notch signaling in the differentiation of the PH, we used a co-culture system of PH with stromal cells that express specific Notch ligands, Delta 1 (Dl1) and Delta 4 (Dl4). The results confirm that, the spleen is an early (E6) vascularized organ and the number of PH in the spleen increases after day E10. In the thymus, the regionalization in cortex and medulla occurs at day E8 and there are no visible neural crest cells during the several embryonic stages studied. We conclude that hematopoietic cells collected from the thymus at day E15 are more differentiated than cells collected from thymus E13. The co-cultures results demonstrated that the Notch ligand Dl1 appears to favor the lymphoid progenitor cells (LPC) proliferation/survival. Thus, the Dl1 ligand may have an important role at the early stages of T cell differentiation. Moreover, these evidences seem to confirm that the undifferentiated LPCs are able to respond more effectively to external stimulus and differentiate into T cells more efficiently.
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Michaels, Lopez Victoria. "Étude de la migration thymique : vers une reconstitution optimale du compartiment T." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB097/document.
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Notre équipe s’intéresse à la différenciation des cellules souches hématopoïétiques (CSH) vers la lignée des lymphocytes T. Contrairement aux autres lignées sanguines, qui se développent dans la MO, les progéniteurs des lymphocytes T doivent terminer leur différenciation dans le thymus. Ma thèse a un double objectif: 1) caractériser les progéniteurs candidats à la reconstitution T pour établir leur contribution à celle-ci et 2) identifier les stades initiaux de la reconstitution T. Nous avons mis en évidence que seul le progéniteur multipotent au stade 3 (MPP3 : Lin- Sca1+ c-Kit+ VCAM1- Flt3+) et le progéniteur commun lymphoïde (CLP : Lin- Sca1lo c-Kitlo IL7Ra+ Flt3-) circulent dans le sang. De plus, nos résultats montrent que les gènes impliqués dans l’engagement T et dans la migration thymique sont uniquement exprimées par la population MPP3 circulante. Cette population est la plus compétente pour générer des précurseurs T (pré-T). Au contraire, les CLPs sont plus efficaces pour la production de différents types de cellules B de la rate. Par la suite, mon projet a consisté à déterminer la proportion de progéniteurs contribuant à la reconstitution T. En effet, le thymus peut être colonisé par différents progéniteurs (LMPP, Lymphoid-primed Multipotent Progenitors, et CLP), mais leur contribution dans la différenciation T reste inconnue et est sujet à controverse. Nous avons utilisé une stratégie innovante pour suivre les progéniteurs avec une séquence d’ADN ou Code Barre (CB) intégrée dans le génome par un vecteur viral. Les résultats préliminaires indiquent qu'une forte fréquence de CBs en provenance de la population LMPP est retrouvée dans le compartiment T thymique. Dans la dernière partie, nous nous sommes intéressés à élucider le premier stade de différenciation T dans le thymus et l’identité cellulaire et moléculaire des premiers migrants thymiques pour comprendre le délai de génération de ce compartiment. La population thymique la plus immature (TN1 : Lin- CD44+ CD25+) présente différentes sous-population selon l’expression de c-Kit et de CD24 chacune de ces différentes populations TN1 pourrait participer à cette reconstitution T. Leur analyse moléculaire montre deux lignées cellulaire selon l’expression de Pu1, dans les TN1 c-Kit+, et de Cd3e, dans la sous-population TN1e (CD24- c-Kit-). En parallèle, pour éclaircir le processus d’engagement des cellules T, ces sous-populations de TN1 ont été étudiées dans différentes conditions de reconstitution : une reconstitution endogène suite à une irradiation sub-létale et une exogène après greffe de MO. Nos résultats permettent de préciser les caractéristiques, propres aux progéniteurs thymiques au stade TN1, qui leur confèrent des compétences à se différencier et à proliférer plus efficacement. Après irradiation ou greffe de MO, le compartiment TN1 est constitué de cellules à faible capacité proliférative. Le thymus en état de reconstitution génère tout d’abord des cellules présentatrice d’antigène (APC) puis les cellules T. Ces deux points suggèrent que les cellules à faible capacité proliférative seront plus aptes à générer des cellules APC plutôt que des cellules T. Il reste à déterminer quel environnement thymique permet le maintien des cellules à faible capacité proliférative, notamment, par rapport à l’expression de Delta-4, de l’IL7 et du ligand c-Kit. Cela va permettre l'identification de facteurs favorisant leur induction et leur expansion. Il nous semble aussi intéressant d’étudier la contribution de la population à faible capacité proliférative, TN1 CD24- c-Kit-, dans la différenciation TWithin the hematopoietic system, hematopoietic stem cells (HSCs) are the only cells with the functional capacity to give rise to all blood lineages and to self-renew for life. These properties and the ability of HSCs to engraft conditioned recipients permitted to apply these cells in regenerative medicine. Like all blood lineages, T cells develop from bone marrow HSC. However, T lineage development requires many weeks, three separate anatomical sites (bone marrow, blood and thymus), many environments and the loss of multiple alternative lineage potentials. Many questions remain to be clarified during this process: do all progenitors have an intrinsic feature of T cell development ? How does this intrinsic potential express ? How the bloodstream contributes to the T cell development ? Which BM progenitor contributes to T cell reconstitution ? What are the characteristics of T cell reconstitution ? We have shown that only the multipotent progenitor in stage 3 (MPP3: Lin- Sca1+ c-Kit+ VCAM1- Flt3+) and a subset of the common lymphoid progenitor (CLP Flt3-: Lin- Sca1lo c-Kitlo IL7Ra+ Flt3-) circulate in the blood. Moreover, our results show that T cell engagement and thymic migration genes are modulated in the circulation, especially up-regulated in the MPP3 circulating subset. This population present a T cell intrinsic potential and is the most competent to generate precursors T (pre-T). On the contrary, CLPs subsets are more efficient for the production of different B cells. Lymphoid primed multipotent progenitor (LMPP, MPP Flt3+) and CLP subsets' respective contributions to the T cell pathway are still being hotly debated. Multiple progenitors in BM have been shown to possess T lineage potential when placed in the thymus. However, it is unlikely that all of them contribute physiologically to thymopoiesis. It was claimed that CLPs are the earliest lymphoid committed progenitor from which B and T lineage cells arise. However, the concept that the CLP is the progenitor population through which all T lymphocytes are derived has been challenged. More specifically, which BM progenitor contribute to the T cell reconstitution ? In order to answer this question, we used an innovative strategy to follow the progenitors with a DNA sequence or Barcode (BC) integrated into the genome by a viral vector. Preliminary results indicate that a high frequency of BCs from the LMPP population is found in the T cell lineage. Finally, we characterized the first stage of T cell differentiation in the thymus by a cellular and molecular asses. We show that the most immature thymic population (TN1: Lin- CD44+ CD25+), at the molecular level, contain two separate lineages, detected by Pu1 (TN1a and b) or CD3e (TN1e) gene expression. In order to clarify the process of T-cell involvement, these TN1 subsets have been studied under different reconstitution conditions: endogenous reconstruction following sub-lethal irradiation and exogenous after bone marrow (BM) graft. In these conditions, the TN1 compartment presents cells with low proliferative capacity and that antigen presenting cells (APC) are the first mature population and thus T cells are generated in second place. These two points suggest that cells with low proliferative capacity will be more apt to generate APC cells rather than T cells. It remains to be determined which thymic environment permits the maintenance of cells with a low proliferative capacity, in particular, with respect to the expression of Delta-4, IL7 and the c-Kit ligand. This will allow the identification of factors favoring their induction and their expansion. It also seems interesting to study the contribution of the population with low proliferative capacity, TN1 CD24- c-Kit-, in the T cell differentiation
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Chabaane, Amna. "Étapes précoces de la lymphopoïèse humaine." Thesis, Université Paris sciences et lettres, 2020. http://www.theses.fr/2020UPSLP027.
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La lymphopoïèse humaine reste mal caractérisée comparativement à son homologue murin. Ceci est dû à l’absence de modèles expérimentaux adéquats et aux difficultés d’accès aux prélèvements primaires de moelle osseuse humaine. Grâce à la caractérisation fine des populations de progéniteurs et précurseurs lymphoïdes présentes dans la moelle osseuse d’animaux greffés, nous avons récemment démontré que la lymphopoïèse humaine suit des voies CD127- ou CD127+ indépendantes qui génèrent une descendance lymphoïde commune et spécifique. Dans cette étude, nous avons mis au point un nouveau test de diversification ex vivo pour analyser leurs relations développementales et étudier les mécanismes qui favorisent l’émergence des progéniteurs lymphoïdes précoces (ELP) CD127- ou CD127+ à partir de leurs ancêtres lympho-mono-dendritiques (LMDP) communs. Les analyses cinétiques montrent que les ELP CD127- ou CD127+ émergent de manière séquentielle des LMDP "précoces" par rapport aux LMDP "tardifs". Le criblage fonctionnel d’une série de 30 récepteur/ligand montre en outre que les ELP CD127- ou CD127+ sont soumis à une régulation différentielle. Alors que les signaux Flt3L, IL27 et Notch1 bloquent l’émergence des ELP CD127+ et polarisent la différenciation lymphoïde vers la voie exclusive CD127-, l’émergence des ELP CD127+ est au contraire favorisée par des conditions de limitation cytokinique et de faibles taux d’expansion cellulaire. Ces résultats indiquent que les ELP CD127- et CD127+ sont soumises à des mécanismes de régulation distincts, selon qu’ils soient extrinsèques ou intrinsèques aux cellules, renforçant ainsi l’architecture dichotomique de la lymphopoïèse humaine proposée précédemment. Ces résultats plaident également en faveur d’une régulation multicouche de la différenciation lympho-myéloïde, remettant en question le modèle continu émergeant de l’hématopoïèseHuman lymphopoiesis remains poorly characterized compared to its murine counterpart. This is due to the lack of adequate experimental models and difficulties in accessing primary bone marrow samples. Thanks to the fine characterization of the populations of lymphoid progenitors and precursors in the bone marrow of transplanted mice, we have recently demonstrated that human lymphopoiesis proceeds along independent CD127- or CD127+ pathways that generate both common and specific lymphoid subsets. In this report, we developed a novel ex vivo diversification assay to analyze their developmental relationships and investigate the mechanisms driving the emergence of the CD127- or CD127+ early lymphoid progenitors (ELPs) from their common lympho-mono-dendritic (LMDP) ancestors. Time-course analyses show that CD127- or CD127+ ELPs emerge sequentially from “early” versus “late” LMDPs. Functional screening of a series of 30 receptor/ligand pairs show in addition that the CD127- or CD127+ ELPs are subjected to a differential regulation. Whereas Flt3L, IL-27 and Notch1 signaling impose a veto on CD127+ ELP emergence and polarize lymphoid differentiation toward exclusive CD127- pathway, the emergence of the CD127+ ELPs is instead favored by limiting cytokine conditions and low cell expansion rates. These new findings indicate that CD127- and CD127+ ELPs are subjected to distinct cell-extrinsic versus cell-intrinsic regulatory mechanisms thereby reinforcing the previously proposed dichotomous architecture of human lymphopoiesis. In as much as they also argue for multi-layered regulation of lympho-myeloid differentiation, our new results challenge the emerging continuous model of hematopoiesis
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Larbi, Aniya. "Les cellules souches embryonnaires humaines, un modèle d’étude des étapes précoces de la lymphopoïèse." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114808.
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Les cellules souches embryonnaires humaines (CSEh) sont des outils puissants pour explorer la genèse des différents tissus de l’organisme, notamment le tissu hématopoïétique. Dans le but d’obtenir des types cellulaires cliniquement utiles, la majorité des travaux se sont concentrés sur l’obtention des cellules hématopoïétiques terminales, notamment des cellules lymphoïdes (lymphocytes B, lymphocyte T et cellules NK), à partir des cellules souches pluripotentes humaines. En revanche, le rendement des cellules hématopoïétiques obtenues dans ce modèle reste faible. D’autre part, les étapes précoces de l’hématopoïèse, notamment l’identification de la cellule souche hématopoïétique (CSH), des progéniteurs myéloïdes et lymphoïdes à partir des cellules souches pluripotentes, sont encore très peu définies. Nous nous sommes intéressés aux étapes précoces de la lymphopoïèse dans le modèle des CSEh. Dans un premier temps, nous avons étudié le rôle de l’homéoprotéine HOXB4 dans l’expansion des progéniteurs NK dérivés des CSEh. Nous avons montré que l’exposition des cellules des corps embryonnaires (EB pour Embryoid Body), dérivées de la différenciation des CSEh, à la lignée MS-5/SP-HOXB4, une lignée modifiée qui exprime constitutivement HOXB4, induit une expansion des progéniteurs NK dérivées des CSEh. De plus, les cellules NK qui en dérivent sont matures et fonctionnelles, de part leur activité cytolytique vis-à-vis d’une lignée érythro-leucémique (K562). Outre l’effet de HOXB4 sur l’expansion des progéniteurs NK, cette étude a permis de démontrer en particulier le rôle de la lignée stromale MS-5 dans l’induction de la spécification lymphoïde à partir des CSEh. Dans un deuxième temps, nous avons analysé plus précisément les étapes précoces de la lymphopoïèse humaine à partir des CSEh. En effet, nous avons montré, au cours de la première partie, que la coculture des cellules dérivées des EB avec MS-5 induit l’expression en surface du CD45RA, un marqueur de spécification lymphoïde, au sein des progéniteurs hématopoïétiques CD34+. Ainsi, sur la base de ces données et des données antérieurs concernant les étapes précoces de la lymphopoïèse humaine fœtale et adulte, nous avons identifié et caractérisé in vitro à partir des CSEh deux populations originales de progéniteurs lymphoïdes précoces multipotents (MELP pour Myeloid Early Lymphoid Progenitor): La progéniteur CD34+CD45RA+CD7+ dont le potentiel de différenciation est biaisé vers le lignage T et NK ; et le progéniteur CD34+CD45RA+CD7- a un potentiel de différenciation biaisé vers les lymphocytes B. Cette étude a un intérêt dans la compréhension du processus de la lymphopoïèse humaine dans le modèle des cellules souches pluripotentes. En perspective, ces données pourraient avoir également un intérêt dans la modélisation de maladie de défauts génétiques de développement du système lymphoïdeHuman embryonic stem cells (hESC) are powerful tools to explore tissue genesis of the organism, especially hematopoietic tissue. In order to obtain cellular types clinically useful, the majority of works have been focalised on final output of hematopoietic cells, especially lymphoid cells (lymphocyte B, lymphocyte T and NK cells), from human pluripotent stem cells. However, the obtained hematopoietic cells yield is very poor. In the other hand, initial steps of hematopoiesis, especially the identification of the hematopoietic stem cell, myeloid and lymphoid progenitors, from pluripotent stem cells, are poorly defined. We were interested to early steps of lymphopoisis in the hESC model. Initially, we studied the role of HOXB4 homeprotein on CSEh-derived NK progenitor. We showed that exposure of embryoid body (EB), derived from hESC, to the modified line that express constitutively HOXB4 “MS-5/SP-HOXB4”, induce hESC-derived NK progenitor expansion. Furthermore, the derived NK cells are mature and fonctionnal, by cytolytic activity on erythro-leucemic line K562. Furthermore the effect of HOXB4 on NK progenitor expansion, this study demonstrated, particularly the role of MS-5 line on the lymphoid specification from hESC.Secondly, we analysed more precisely the early steps of human lymphopoiesis from hESC. We showed, in the first part, that MS-5 coculture of the EB-derived cells induce surface expression of CD45RA (marker of lymphoid specification) on hematopoietic progenitor CD34+. Thus, on the basis of these data and previous data concerning the initial steps of fetal and adult lymphopoiesis, we identified and characterized in vitro from hESC, two populations of multipotent early lymphoid progenitor (MELP): the CD34+CD45RA+CD7+ progenitor whose the differentiation potential is biased to T and NK lineage, and the CD34+CD45RA+CD7- progenitor has differentiation potential biased to B lineage. This study is essential in understanding of normal and pathological lymphopoisis process in pluripotent stem cells model. Additionally, this study paves the way for the modeling of genetic disorders of lymphoid system
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Ghaedi, Maryam. "Common lymphoid progenitor-independent pathways of innate and T lymphocyte development." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/52878.
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All lymphocytes are thought to develop from a single population of committed lymphoid progenitors termed common lymphoid progenitors (CLPs). However, upstream progenitors termed lymphoid-primed multi-potent progenitors (LMPPs) are known to be more efficient than CLPs in differentiating into T cells and group 2 innate lymphoid cells (ILC2s), suggesting alternative pathways of their development. Here, we have divided LMPPs into CD127- (LMPP-s) and CD127+ (LMPP+s) subsets and compared them with CLPs. Adult LMPP+s are the most efficient progenitors for T cells and ILCs in transplantation assays, and lineage tracking by the recombinase expression also suggests that most ILC2s and NK cells develop from LMPPs independent of CLPs. In the neonatal period CLPs are rare and, unlike prominent neonatal LMPP+s, incapable of differentiating into ILC2s and T cells while their development is highly active. These results suggest non-linear pathways of innate and T lymphocyte development from LMPP+s with limited CLP contributions.Medicine, Faculty of
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Leyland, R. J. "Lineage relationship analysis of lymphoid progenitor subsets in the bone marrow of naïve mice and during inflammation." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1322960/.
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During haematopoiesis multipotent stem cells generate all cellular components of the blood including lymphocytes. Despite great progress in the isolation of lineage restricted progenitors, the exact precursor-product relationship of these subsets remains poorly understood. In particular the exact branch point of T- and B-cell development in the bone marrow has not been unequivocally mapped. The aim of my project was to investigate the developmental relationship of various progenitor subsets in normal mice and during an acute inflammation. In order to permanently identify all cells which emanated from early lymphoid compartments we generated a mouse model in which a Cre recombinase was inserted into the Rag1 locus and functional Cre activity would result in activation of an eYFP reporter. Expression of the reporter was found in all T- and B-cells and in a significant subset of NK-cells and dendritic cells. Furthermore this model allowed the prospective isolation of an ‘ELP analogue’ and two subsets of CLPs on the basis of their reporter expression. Functional analysis of these subsets in vivo demonstrated comparable developmental properties with slightly different kinetics. Furthermore, in vitro analysis of isolated progenitors established that reporter-positive CLPs were significantly more advanced in their commitment to the B-cell lineage. We extended our studies by investigating the impact of an acute systemic inflammation on the size and composition of early haemato-lymphoid subsets. Administration of LPS or heat-inactivated E. coli to mice in vivo resulted in a complete halt of bone marrow lymphopoiesis. In addition, a marked decrease in the number of myeloid progenitors accompanied by upregulation of Sca-1 on haematopoietic progenitors was observed. These inflammation-induced changes were found to be mainly caused by IFNγ and to a lesser extend by TNFα, thus identifying these cytokines as key mediators for the infection-induced regulation of haematopoiesis.
Book chapters on the topic "Lymphoid progenitors"
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Ezine, Sophie, Laetitia Gautreau, Aude Parcelier, and Bruno Canque. "Developmental Biology of Mammalian T-Cell Progenitors: From Early Lymphoid Progenitors to Thymus-Colonizing Cells." In Hematopoietic Stem Cell Biology, 93–116. Totowa, NJ: Humana Press, 2009. http://dx.doi.org/10.1007/978-1-60327-347-3_4.
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Scott, Edward W. "The Role of PU.1 in the Regulation of Lymphoid and Myeloid Hematopoietic Progenitors." In Molecular Biology of B-Cell and T-Cell Development, 111–26. Totowa, NJ: Humana Press, 1998. http://dx.doi.org/10.1007/978-1-4757-2778-4_7.
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Scherle, P. A., and O. N. Witte. "Functionality of Clonal Lymphoid Progenitor Cells Expressing the P210 BCR/ABL Oncogene." In Current Topics in Microbiology and Immunology, 189–95. Berlin, Heidelberg: Springer Berlin Heidelberg, 1990. http://dx.doi.org/10.1007/978-3-642-75889-8_24.
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Haas, R., H. Goldschmidt, R. Möhle, S. Frühauf, S. Hohaus, B. Witt, U. Mende, M. Flentje, M. Wannenmacher, and W. Hunstein. "High-dose Therapy and Autografting with Mobilized Peripheral Blood Progenitor Cells in Patients with Malignant Lymphoma." In Acute Leukemias V, 398–404. Berlin, Heidelberg: Springer Berlin Heidelberg, 1996. http://dx.doi.org/10.1007/978-3-642-78907-6_67.
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Lemoli, Roberto M., Alessandra Fortuna, Miriam Fogli, Gianantonio Rosti, Filippo Gherlinzoni, Giuseppe Visani, Lucia Catani, Alessandro Gozzetti, and Sante Tura. "Combined Use of Growth Factors to Stimulate the Proliferation of Hematopoietic Progenitor Cells after Autologous Bone Marrow Transplantation (ABMT) for Lymphoma Patients." In Molecular Biology of Hematopoiesis 5, 11–20. Boston, MA: Springer US, 1996. http://dx.doi.org/10.1007/978-1-4613-0391-6_2.
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Hardy, R. R., J. D. Kemp, and K. Hayakawa. "Analysis of Lymphoid Population in Scid Mice; Detection of a Potential B Lymphocyte Progenitor Population Present at Normal Levels in Scid Mice by Three Color Flow Cytometry With B220 and S7." In Current Topics in Microbiology and Immunology, 19–25. Berlin, Heidelberg: Springer Berlin Heidelberg, 1989. http://dx.doi.org/10.1007/978-3-642-74974-2_3.
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Crooks, Gay M. "Common Lymphoid Progenitors." In Handbook of Stem Cells, 347–53. Elsevier, 2004. http://dx.doi.org/10.1016/b978-012436643-5/50123-1.
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Bendari, Mounia, Sofia Sraidi, and Nisrine Khoubila. "Genetic Abnormalities in ALL." In Cytogenetics - Classical and Molecular Strategies for Analysing Heredity Material. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.97429.
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Acute lymphoblastic leukemia (ALL), can be defined by a family of genetically heterogeneous lymphoid neoplasms derived from B- and T-lymphoid progenitors. ALL constitutes the most common childhood cancer, due to an overproduction of immature lymphoid hematopoietic cells. Genetic analyzes currently provides important information for classifying patients into prognostic groups, genetic analysis also helps to understand the mechanisms of relapse, pharmacogenetics and the development of new potential therapeutic targets, which should help to further improve the results of leukemia. In fact, the new techniques in molecular cytogenetic permits to identify new cryptic abnormalities, these discoveries have led to the development of new therapeutic protocols. The role of cytogenetic analysis is crucial on ALL patient’s management. Karyotyping coupled with FISH analysis identifies recurrent chromosomal abnormalities in ALL, many of these abnormalities have prognostic and treatment impact. This chapter summarizes chromosomal abnormalities that are common and classify ALL according to the World Health Organization (WHO) classifications (2016 revision). We will present the main genetic modifications recently identified as well as the sequence mutations which have helped in the elucidation of the pathogenesis of ALL.
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Paige, Christopher J., and Roland H. Gisler. "Adherent layer-dependent development of B cell progenitors in semisolid agar." In Immunochemical Techniques Part K: In Vitro Models of B and T Cell Functions and Lymphoid Cell Receptors, 251–57. Elsevier, 1987. http://dx.doi.org/10.1016/0076-6879(87)50082-9.
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Becerra Becerra, Edgardo, and Guadalupe García-Alcocer. "MicroRNAs and Their Role in Acute Lymphoblastic Leukemia." In Acute Leukemias [Working Title]. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.94960.
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Acute lymphoblastic leukemia (ALL) has been established as the most common acute leukemia in children, accounting for 80–85% of cases. ALL occurs mostly in children and it is considered as a high-risk disease in the elderlies. ALL is characterized by a clonal disorder where the normal hematopoiesis is replaced by a malignant clonal expansion of lymphoid progenitors. Although many therapeutic strategies have been established to treat ALL leading to improved survival rates, the short-term and long-term complications derived from treatment toxicity represent a critical risk for patients. The treatment-related toxicity suggests a need for the development of new therapy strategies to effectively treat high-risk and low-risk disease. Nowadays, an important approach is focused on the identification of molecules involved in the mechanisms that lead to leukemia generation and progression to determine potential targets at the transcriptional level. MicroRNAs (miRNAs) are a group of key molecules that regulate signaling pathways related to lymphopoiesis. miRNAs participate in the regulation of hematopoietic differentiation and proliferation, as well as their activity. The present review details the recompilation of evidences about the relation between miRNAs and lymphopoiesis, ALL development and progression in order to propose and explore novel strategies to modulate ALL-related miRNA levels as a therapeutic approach.
Conference papers on the topic "Lymphoid progenitors"
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Woodcroft, Mark W., Takyuki Murase, and David P. LeBrun. "Abstract 3097: The leukemogenic protein E2A-PBX1 blocks B-lymphoid commitment in early hematopoietic progenitors." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-3097.
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Lechman, Eric R., Karin G. Hermans, Stephanie Dobson, Kolja Eppert, Mark Minden, and John E. Dick. "Abstract 2292: Enforced expression of miR-125b promotes the in vivo expansion of human Lin- CB multi-lymphoid progenitors (MLP) and AML leukemia stem cells." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-2292.
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Ito, Daisuke, Anne C. Avery, Nicola J. Mason, Tim D. O'Brien, and Jaime F. Modiano. "Abstract 4307: Characterization of a novel lymphoid progenitor population with predictive value in canine non-Hodgkin lymphoma." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-4307.
Full textReports on the topic "Lymphoid progenitors"
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Cooper, Laurence, and Rita Young. Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical, Hematompoietic Progenitor-Cell Transplant. Fort Belvoir, VA: Defense Technical Information Center, May 2008. http://dx.doi.org/10.21236/ada487262.
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Cooper, Laurence. Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical, Hematompoietic Progenitor-Cell Transplant. Fort Belvoir, VA: Defense Technical Information Center, May 2011. http://dx.doi.org/10.21236/ada560655.
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