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1

Gallego-Perez, Daniel, Jose J. Otero, Catherine Czeisler, Junyu Ma, Cristina Ortiz, Patrick Gygli, Fay Patsy Catacutan, et al. "Deterministic transfection drives efficient nonviral reprogramming and uncovers reprogramming barriers." Nanomedicine: Nanotechnology, Biology and Medicine 12, no. 2 (February 2016): 399–409. http://dx.doi.org/10.1016/j.nano.2015.11.015.

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2

Deng, Wenbin. "AID in reprogramming: Quick and efficient." BioEssays 32, no. 5 (April 14, 2010): 385–87. http://dx.doi.org/10.1002/bies.201000014.

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3

Horna, David, Juan Carlos Ramírez, Anna Cifuentes, Antonio Bernad, Salvador Borrós, and Manuel A. González. "Efficient Cell Reprogramming Using Bioengineered Surfaces." Advanced Healthcare Materials 1, no. 2 (February 16, 2012): 177–82. http://dx.doi.org/10.1002/adhm.201200017.

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4

Kang, Martin H., Jiabiao Hu, Richard E. Pratt, Conrad P. Hodgkinson, Aravind Asokan, and Victor J. Dzau. "Optimizing delivery for efficient cardiac reprogramming." Biochemical and Biophysical Research Communications 533, no. 1 (November 2020): 9–16. http://dx.doi.org/10.1016/j.bbrc.2020.08.104.

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5

Miller, Chris, and Christian Poellabauer. "Reliable and efficient reprogramming in sensor networks." ACM Transactions on Sensor Networks 7, no. 1 (August 2010): 1–32. http://dx.doi.org/10.1145/1806895.1806901.

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6

Kulkarni, Sandeep, and Limin Wang. "Energy-efficient multihop reprogramming for sensor networks." ACM Transactions on Sensor Networks 5, no. 2 (March 2009): 1–40. http://dx.doi.org/10.1145/1498915.1498922.

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7

Hermann, Andreas, Jeong Beom Kim, Sumitra Srimasorn, Holm Zaehres, Peter Reinhardt, Hans R. Schöler, and Alexander Storch. "Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors." Stem Cells International 2016 (2016): 1–6. http://dx.doi.org/10.1155/2016/4736159.

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Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of the transcription factors OCT4, SOX2, KLF4, and c-Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk of chromosomal disruption and to simplify reprogramming, several studies demonstrated that a reduced set of reprogramming factors is sufficient to generate iPSC. We recently showed that a reduction of reprogramming factors in murine cells not only reduces reprogramming efficiency but also may worsen subsequent differentiation. To prove whether this is also true for human cells, we compared the efficiency of neuronal differentiation of iPSC generated from fetal human neural stem cells with either one (OCT4;hiPSC1F-NSC) or two (OCT4, KLF4;hiPSC2F-NSC) reprogramming factors with iPSC produced from human fibroblasts using three (hiPSC3F-FIB) or four reprogramming factors (hiPSC4F-FIB). After four weeks of coculture with PA6 stromal cells, neuronal differentiation ofhiPSC1F-NSCandhiPSC2F-NSCwas as efficient asiPSC3F-FIBoriPSC4F-FIB. We conclude that a reduction of reprogramming factors in human cells does reduce reprogramming efficiency but does not alter subsequent differentiation into neural lineages. This is of importance for the development of future application of iPSC in cell replacement therapies.
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8

Yu, Junying, Kevin Fongching Chau, Maxim A. Vodyanik, Jinlan Jiang, and Yong Jiang. "Efficient Feeder-Free Episomal Reprogramming with Small Molecules." PLoS ONE 6, no. 3 (March 1, 2011): e17557. http://dx.doi.org/10.1371/journal.pone.0017557.

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9

Hu, Kejin, Junying Yu, Kran Suknuntha, Shulan Tian, Karen Montgomery, Kyung-Dal Choi, Ron Stewart, James A. Thomson, and Igor I. Slukvin. "Efficient generation of transgene-free induced pluripotent stem cells from normal and neoplastic bone marrow and cord blood mononuclear cells." Blood 117, no. 14 (April 7, 2011): e109-e119. http://dx.doi.org/10.1182/blood-2010-07-298331.

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Abstract Reprogramming blood cells to induced pluripotent stem cells (iPSCs) provides a novel tool for modeling blood diseases in vitro. However, the well-known limitations of current reprogramming technologies include low efficiency, slow kinetics, and transgene integration and residual expression. In the present study, we have demonstrated that iPSCs free of transgene and vector sequences could be generated from human BM and CB mononuclear cells using nonintegrating episomal vectors. The reprogramming described here is up to 100 times more efficient, occurs 1-3 weeks faster compared with the reprogramming of fibroblasts, and does not require isolation of progenitors or multiple rounds of transfection. Blood-derived iPSC lines lacked rearrangements of IGH and TCR, indicating that their origin is non–B- or non–T-lymphoid cells. When cocultured on OP9, blood-derived iPSCs could be differentiated back to the blood cells, albeit with lower efficiency compared to fibroblast-derived iPSCs. We also generated transgene-free iPSCs from the BM of a patient with chronic myeloid leukemia (CML). CML iPSCs showed a unique complex chromosomal translocation identified in marrow sample while displaying typical embryonic stem cell phenotype and pluripotent differentiation potential. This approach provides an opportunity to explore banked normal and diseased CB and BM samples without the limitations associated with virus-based methods.
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10

Bussmann, Lars H., Alexis Schubert, Thien Phong Vu Manh, Luisa De Andres, Sabrina C. Desbordes, Maribel Parra, Timo Zimmermann, et al. "A Robust and Highly Efficient Immune Cell Reprogramming System." Cell Stem Cell 5, no. 5 (November 2009): 554–66. http://dx.doi.org/10.1016/j.stem.2009.10.004.

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11

De, P., Yonghe Liu, and S. K. Das. "Energy-Efficient Reprogramming of a Swarm of Mobile Sensors." IEEE Transactions on Mobile Computing 9, no. 5 (May 2010): 703–18. http://dx.doi.org/10.1109/tmc.2009.159.

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12

Dong, Chuchu, and Fengqi Yu. "An efficient network reprogramming protocol for wireless sensor networks." Computer Communications 55 (January 2015): 41–50. http://dx.doi.org/10.1016/j.comcom.2014.08.017.

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13

Steinle, Heidrun, Marbod Weber, Andreas Behring, Ulrike Mau-Holzmann, Christian Schlensak, Hans Peter Wendel, and Meltem Avci-Adali. "Generation of iPSCs by Nonintegrative RNA-Based Reprogramming Techniques: Benefits of Self-Replicating RNA versus Synthetic mRNA." Stem Cells International 2019 (June 19, 2019): 1–16. http://dx.doi.org/10.1155/2019/7641767.

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The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is gaining in importance in the fields of regenerative medicine, tissue engineering, and disease modeling. Patient-specific iPSCs have as an unlimited cell source a tremendous potential for generating various types of autologous cells. For the future clinical applicability of these iPSC-derived cells, the generation of iPSCs via nongenome integrating methods and the efficient reprogramming of patients’ somatic cells are required. In this study, 2 different RNA-based footprint-free methods for the generation of iPSCs were compared: the use of synthetic modified messenger RNAs (mRNAs) or self-replicating RNAs (srRNAs) encoding the reprogramming factors and GFP. Using both RNA-based methods, integration-free iPSCs without genomic alterations were obtained. The pluripotency characteristics identified by specific marker detection and the in vitro and in vivo trilineage differentiation capacity were comparable. Moreover, the incorporation of a GFP encoding sequence into the srRNA enabled a direct and convenient monitoring of the reprogramming procedure and the successful detection of srRNA translation in the transfected cells. Nevertheless, the use of a single srRNA to induce pluripotency was less time consuming, faster, and more efficient than the daily transfection of cells with synthetic mRNAs. Therefore, we believe that the srRNA-based approach might be more appropriate and efficient for the reprogramming of different types of somatic cells for clinical applications.
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14

Park, Joo Hyun, Laurence Daheron, Sibel Kantarci, Byung Seok Lee, and Jose M. Teixeira. "Human Endometrial Cells Express Elevated Levels of Pluripotent Factors and Are More Amenable to Reprogramming into Induced Pluripotent Stem Cells." Endocrinology 152, no. 3 (March 1, 2011): 1080–89. http://dx.doi.org/10.1210/en.2010-1072.

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The human endometrium is a tissue with remarkable plasticity and regenerative capacity. Additionally, endometrial cells can be retrieved using minimally invasive procedures, which makes them an ideal source for reprogramming into a pluripotent state. Endometrial cells were obtained from donors in their fifth decade and reprogrammed into induced pluripotent stem (iPS) cells using retroviral transduction with SOX2, OCT4, KLF4, and MYC. The human endometrial cells displayed accelerated expression of endogenous NANOG and OCT4 during reprogramming compared with neonatal skin fibroblasts. As a result, iPS cell colonies that could be subcultured and propagated were established as early as 12 d after transduction rather than the usually reported 3–4 wk for other cell types. After 3 wk of reprogramming, the human endometrial cells also yielded significantly higher numbers of iPS colonies in comparison with the neonatal skin fibroblasts. Although the efficiency of iPS colony formation varied depending on the donor, the basal level of endogenous expression of the defined factors was positively correlated with reprogramming efficiency. The reprogramming resulted in an average colony-forming efficiency of 0.49 ± 0.10%, with a range from 0.31–0.66%, compared with the neonatal skin fibroblasts, resulting in an average efficiency of 0.03 ± 0.00% per transduction, with a range from 0.02–0.03%. Our studies show that the human endometrium expresses elevated levels of pluripotent factors, which with additional defined factors, results in significantly more efficient and accelerated generation of induced pluripotent stem cells compared with conventional somatic cells.
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15

Paoletti, Camilla, Carla Divieto, and Valeria Chiono. "Impact of Biomaterials on Differentiation and Reprogramming Approaches for the Generation of Functional Cardiomyocytes." Cells 7, no. 9 (August 21, 2018): 114. http://dx.doi.org/10.3390/cells7090114.

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The irreversible loss of functional cardiomyocytes (CMs) after myocardial infarction (MI) represents one major barrier to heart regeneration and functional recovery. The combination of different cell sources and different biomaterials have been investigated to generate CMs by differentiation or reprogramming approaches although at low efficiency. This critical review article discusses the role of biomaterial platforms integrating biochemical instructive cues as a tool for the effective generation of functional CMs. The report firstly introduces MI and the main cardiac regenerative medicine strategies under investigation. Then, it describes the main stem cell populations and indirect and direct reprogramming approaches for cardiac regenerative medicine. A third section discusses the main techniques for the characterization of stem cell differentiation and fibroblast reprogramming into CMs. Another section describes the main biomaterials investigated for stem cell differentiation and fibroblast reprogramming into CMs. Finally, a critical analysis of the scientific literature is presented for an efficient generation of functional CMs. The authors underline the need for biomimetic, reproducible and scalable biomaterial platforms and their integration with external physical stimuli in controlled culture microenvironments for the generation of functional CMs.
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16

Arnholdt-Schmitt, Birgit, José H. Costa, and Dirce Fernandes de Melo. "AOX – a functional marker for efficient cell reprogramming under stress?" Trends in Plant Science 11, no. 6 (June 2006): 281–87. http://dx.doi.org/10.1016/j.tplants.2006.05.001.

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17

Krasniewski, Mark D., Rajesh Krishna Panta, Saurabh Bagchi, Chin-Lung Yang, and William J. Chappell. "Energy-efficient on-demand reprogramming of large-scale sensor networks." ACM Transactions on Sensor Networks 4, no. 1 (January 2008): 1–38. http://dx.doi.org/10.1145/1325651.1325653.

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18

Baek, Soonbong, Xiaoyuan Quan, Soochan Kim, Christopher Lengner, Jung-Keug Park, and Jongpil Kim. "Electromagnetic Fields Mediate Efficient Cell Reprogramming into a Pluripotent State." ACS Nano 8, no. 10 (October 2014): 10125–38. http://dx.doi.org/10.1021/nn502923s.

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19

Panta, Rajesh Krishna, Saurabh Bagchi, and Issa M. Khalil. "Efficient wireless reprogramming through reduced bandwidth usage and opportunistic sleeping." Ad Hoc Networks 7, no. 1 (January 2009): 42–62. http://dx.doi.org/10.1016/j.adhoc.2007.11.015.

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20

Lee, Jieun, Nazish Sayed, Arwen Hunter, Kin Fai Au, Wing H. Wong, Edward S. Mocarski, Renee Reijo Pera, Eduard Yakubov, and John P. Cooke. "Activation of Innate Immunity Is Required for Efficient Nuclear Reprogramming." Cell 151, no. 3 (October 2012): 547–58. http://dx.doi.org/10.1016/j.cell.2012.09.034.

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21

Ye, Huahu, and Qiwei Wang. "Efficient Generation of Non-Integration and Feeder-Free Induced Pluripotent Stem Cells from Human Peripheral Blood Cells by Sendai Virus." Cellular Physiology and Biochemistry 50, no. 4 (2018): 1318–31. http://dx.doi.org/10.1159/000494589.

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Background/Aims: Induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, disease modeling, and drug development. Thus, generation of non-integration and feeder-free iPSCs is highly desirable for clinical applications. Peripheral blood mononuclear cells (PBMCs) are an attractive resource for cell reprogramming because of their properties of easy accessibility and the limited invasiveness of blood collection. However, derivation of iPSCs is technically demanding due to the low reprogramming efficiency and nonadherent features of PBMCs. Methods: iPSCs were generated from PBMCs using non-integrative Sendai viruses carrying the reprogramming factors Oct4, Sox2, Klf4, and cMyc. The derived iPSCs were fully characterized at the levels of gene and protein, and then they were transplanted into immunocompromised mice for evaluation of in vivo differentiation potential. Three types of extracellular substrates (Geltrex, vitronectin, and rhLaminn-521) were tested for their influences on cell reprogramming under feeder-free conditions. We also sought to establish approaches to efficient cell recovery post-thaw and single cell passaging of iPSCs employing Rock inhibitors. Results: iPSCs were efficiently generated from PBMCs under feeder-free conditions. The derived iPSCs proved to be pluripotent and transgene-free. Furthermore, they demonstrated multi-lineage differentiation potentials when transplanted into immunocompromised mice. Among the three substrates, Geltrex and rhLaminin-521 could effectively support the initial cell reprogramming process, but vitronectin failed. However, the vitronectin, similar to Geltrex and rhLaminin-521, could effectively maintain cell growth and expansion of passaged iPSCs. In addition, RevitaCell supplement (RVC) was more potent on cell recovery post-thaw than Y-27632. And RVC and Y-27632 could significantly increase the cell survival when the cells were passaged in single cells, and they showed comparable effectiveness on cell recovery. Conclusion: We have successfully derived non-integration and feeder-free human iPSCs from peripheral blood cells, and established effective strategies for efficient cell recovery and single cell passaging. This study will pave the way to the derivation of clinical-grade human iPSCs for future clinical applications.
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22

Tendean, Marshel, Yudi Her Oktaviono, and Ferry Sandra. "Cardiomyocyte Reprogramming: A Potential Strategy for Cardiac Regeneration." Molecular and Cellular Biomedical Sciences 1, no. 1 (March 1, 2017): 1. http://dx.doi.org/10.21705/mcbs.v1i1.5.

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Heart disease is the leading cause of death worldwide. Within decades a limited process of cardiac cell regeneration was under observation. Embryonic stem cell (ESC) shows great potential for cell and tissue regeneration. Studies indicate that ESC has the potential to enhance myocardial perfusion and/or contractile performance in ischemic myocardium. However there is still challenge to evaluate the issues of teratoma. Then induced pluripotent stem cell was invented by introducing four transcriptional factors (Oct4, Sox2, Klf4, c-Myc). iPSC was created from murine fibroblast and then differentiated into cardiomyocyte. Reprogramming the adult cell could be performed in full, partial or direct reprogramming. Several studies add the significance by reprogramming the cells through more efficient techniques. However several limitations are still remained.Keywords: cardiomyocyte, reprogramming, iPSC, fibroblast
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23

Yuan, Xia, Chen Zhang, Ruifeng Zhao, Jingyi Jiang, Xiang Shi, Ming Zhang, Hongyan Sun, et al. "Glycolysis Combined with Core Pluripotency Factors to Promote the Formation of Chicken Induced Pluripotent Stem Cells." Animals 11, no. 2 (February 6, 2021): 425. http://dx.doi.org/10.3390/ani11020425.

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Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) in vitro. Previously, a lentivirus induction strategy of introducing Oct4, Sox2, Nanog and Lin28 (OSNL) into the iPSC process has been shown as a possible way to produce chicken iPSCs from chicken embryonic fibroblasts, but the induction efficiency of this method was found to be significantly limiting. In order to help resolve this efficiency obstacle, this study seeks to clarify the associated regulation mechanisms and optimizes the reprogramming strategy of chicken iPSCs. This study showed that glycolysis and the expression of glycolysis-related genes correlate with a more efficient reprogramming process. At the same time, the transcription factors Oct4, Sox2 and Nanog were found to activate the expression of glycolysis-related genes. In addition, we introduced two small-molecule inhibitors (2i-SP) as a “glycolysis activator” together with the OSNL cocktail, and found that this significantly improved the induction efficiency of the iPSC process. As such, the study identifies direct molecular connections between core pluripotency factors and glycolysis during the chicken iPSC induction process and, with its results, provides a theoretical basis and technical support for chicken somatic reprogramming.
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Liu, Kuangpin, Wei Ma, Chunyan Li, Junjun Li, Xingkui Zhang, Jie Liu, Wei Liu, et al. "Advances in transcription factors related to neuroglial cell reprogramming." Translational Neuroscience 11, no. 1 (February 20, 2020): 17–27. http://dx.doi.org/10.1515/tnsci-2020-0004.

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AbstractNeuroglial cells have a high level of plasticity, and many types of these cells are present in the nervous system. Neuroglial cells provide diverse therapeutic targets for neurological diseases and injury repair. Cell reprogramming technology provides an efficient pathway for cell transformation during neural regeneration, while transcription factor-mediated reprogramming can facilitate the understanding of how neuroglial cells mature into functional neurons and promote neurological function recovery.
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25

Ovchinnikova, Leyla A., Stanislav S. Terekhov, Rustam H. Ziganshin, Dmitriy V. Bagrov, Ioanna N. Filimonova, Arthur O. Zalevsky, and Yakov A. Lomakin. "Reprogramming Extracellular Vesicles for Protein Therapeutics Delivery." Pharmaceutics 13, no. 6 (May 21, 2021): 768. http://dx.doi.org/10.3390/pharmaceutics13060768.

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Delivering protein therapeutics specifically into target cells and tissues is a promising avenue in medicine. Advancing this process will significantly enhance the efficiency of the designed drugs. In this regard, natural membrane-based systems are of particular interest. Extracellular vesicles (EVs), being the bilayer lipid particles secreted by almost all types of cells, have several principal advantages: biocompatibility, carrier stability, and blood–brain barrier penetrability, which make them a perspective tool for protein therapeutic delivery. Here, we evaluate the engineered genetically encoded EVs produced by a human cell line, which allow efficient cargo loading. In the devised system, the protein of interest is captured by self-assembling structures, i.e., “enveloped protein nanocages” (EPN). In their turn, EPNs are encapsulated in fusogenic EVs by the overexpression of vesicular stomatitis virus G protein (VSV-G). The proteomic profiles of different engineered EVs were determined for a comprehensive evaluation of their therapeutic potential. EVs loading mediated by bio-safe Fos–Jun heterodimerization demonstrates an increased efficacy of active cargo loading and delivery into target cells. Our results emphasize the outstanding technological and biomedical potential of the engineered EV systems, including their application in adoptive cell transfer and targeted cell reprogramming.
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26

Merling, Randall K., Colin L. Sweeney, Uimook Choi, Suk See De Ravin, Timothy G. Myers, Francisco Otaizo-Carrasquero, Jason Pan, et al. "Transgene-free iPSCs generated from small volume peripheral blood nonmobilized CD34+ cells." Blood 121, no. 14 (April 4, 2013): e98-e107. http://dx.doi.org/10.1182/blood-2012-03-420273.

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27

Poleganov, Marco Alexander, Sarah Eminli, Tim Beissert, Stephanie Herz, Jung-Il Moon, Johanna Goldmann, Arianne Beyer, et al. "Efficient Reprogramming of Human Fibroblasts and Blood-Derived Endothelial Progenitor Cells Using Nonmodified RNA for Reprogramming and Immune Evasion." Human Gene Therapy 26, no. 11 (November 2015): 751–66. http://dx.doi.org/10.1089/hum.2015.045.

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28

Zhang, Yu, Xing She Zhou, Yee Wei Law, and Marimuthu Palaniswami. "Efficient Homomorphic Hashing Approach for Secure Reprogramming in Wireless Sensor Networks." International Journal of Wireless and Microwave Technologies 2, no. 1 (February 15, 2012): 1–9. http://dx.doi.org/10.5815/ijwmt.2012.01.01.

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29

Oh, Seung-ick, Hang-soo Park, Insik Hwang, Han-kyul Park, Kyung-Ah Choi, Hyesun Jeong, Suhng Wook Kim, and Sunghoi Hong. "Efficient Reprogramming of Mouse Fibroblasts to Neuronal Cells including Dopaminergic Neurons." Scientific World Journal 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/957548.

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Somatic cells were directly converted to functional neurons through the use of a combination of transcription factors, including Ascl1, Brn2, and Myt1l. However, a major limitation is the lack of a reliable source of cell-replacement therapy for neurological diseases. Here, we show that a combination of the transcription factors Ascl1 and Nurr1 (AN) and neurotrophic factors including SHH and FGF8b directly reprogrammed embryonic mouse fibroblasts to induced neuronal (iN) cells: pan-neuronal cells and dopaminergic (DA) neurons under our systematic cell culture conditions. Reprogrammed cells showed the morphological properties of neuronal cells. Additionally, cells were analyzed using various markers, including Tuj1 and Map2 for neuronal cells and Lmx1a, Th, Aadc and Vmat2 for DA neurons in our immunostaining and reverse transcription (RT)-PCR experiments. We found that a combination of transcription factors and neurotrophic factors could directly reprogram fibroblasts to neuronal cells including DA neurons. Various types of reprogrammed cells are promising cell sources for cell-based therapy of neurological disorders like Parkinson’s disease and spinal cord injury.
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Kim, Seung-Ku, Jae-Ho Lee, Kyeong Hur, Kwang-il Hwang, and Doo-Seop Eom. "Tiny module-linking for energy-efficient reprogramming in wireless sensor networks." IEEE Transactions on Consumer Electronics 55, no. 4 (November 2009): 1914–20. http://dx.doi.org/10.1109/tce.2009.5373750.

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Wang, Weijian, Xiao Yu, Yongjun Wei, Rodrigo Ledesma-Amaro, and Xiao-Jun Ji. "Reprogramming the metabolism of Klebsiella pneumoniae for efficient 1,3-propanediol production." Chemical Engineering Science 236 (June 2021): 116539. http://dx.doi.org/10.1016/j.ces.2021.116539.

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Apura, Patrícia, Susana Domingues, Sandra C. Viegas, and Cecília M. Arraiano. "Reprogramming bacteria with RNA regulators." Biochemical Society Transactions 47, no. 5 (October 23, 2019): 1279–89. http://dx.doi.org/10.1042/bst20190173.

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Abstract The revolution of genomics and growth of systems biology urged the creation of synthetic biology, an engineering discipline aiming at recreating and reprogramming cellular functions for industrial needs. There has been a huge effort in synthetic biology to develop versatile and programmable genetic regulators that would enable the precise control of gene expression. Synthetic RNA components have emerged as a solution, offering a diverse range of programmable functions, including signal sensing, gene regulation and the modulation of molecular interactions. Owing to their compactness, structure and way of action, several types of RNA devices that act on DNA, RNA and protein have been characterized and applied in synthetic biology. RNA-based approaches are more ‘economical' for the cell, since they are generally not translated. These RNA-based strategies act on a much shorter time scale than transcription-based ones and can be more efficient than protein-based mechanisms. In this review, we explore these RNA components as building blocks in the RNA synthetic biology field, first by explaining their natural mode of action and secondly discussing how these RNA components have been exploited to rewire bacterial regulatory circuitry.
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Kikyo, N., and A. P. Wolffe. "Reprogramming nuclei: insights from cloning, nuclear transfer and heterokaryons." Journal of Cell Science 113, no. 1 (January 1, 2000): 11–20. http://dx.doi.org/10.1242/jcs.113.1.11.

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Mammals and amphibians can be cloned following the transfer of embryonic nuclei into enucleated eggs or oocytes. As nuclear functions become more specialized in the differentiated cells of an adult, successful cloning using these nuclei as donors becomes more difficult. Differentiation involves the assembly of specialized forms of repressive chromatin including linker histones, Polycomb group proteins and methyl-CpG-binding proteins. These structures compartmentalize chromatin into functional domains and maintain the stability of the differentiated state through successive cell divisions. Efficient cloning requires the erasure of these structures. The erasure can be accomplished through use of molecular chaperones and enzymatic activities present in the oocyte, egg or zygote. We discuss the mechanisms involved in reprogramming nuclei after nuclear transfer and compare them with those that occur during remodeling of somatic nuclei after heterokaryon formation. Finally we discuss how one might alter the properties of adult nuclei to improve the efficiency of cloning.
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Tanihara, Fuminori, Tatsuya Takemoto, Eri Kitagawa, Shengbin Rao, Lanh Thi Kim Do, Akira Onishi, Yukiko Yamashita, et al. "Somatic cell reprogramming-free generation of genetically modified pigs." Science Advances 2, no. 9 (September 2016): e1600803. http://dx.doi.org/10.1126/sciadv.1600803.

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Genetically modified pigs for biomedical applications have been mainly generated using the somatic cell nuclear transfer technique; however, this approach requires complex micromanipulation techniques and sometimes increases the risks of both prenatal and postnatal death by faulty epigenetic reprogramming of a donor somatic cell nucleus. As a result, the production of genetically modified pigs has not been widely applied. We provide a simple method for CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing in pigs that involves the introduction of Cas9 protein and single-guide RNA into in vitro fertilized zygotes by electroporation. The use of gene editing by electroporation of Cas9 protein (GEEP) resulted in highly efficient targeted gene disruption and was validated by the efficient production of Myostatin mutant pigs. Because GEEP does not require the complex methods associated with micromanipulation for somatic reprogramming, it has the potential for facilitating the genetic modification of pigs.
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35

Kumar, Satish, Joanne E. Curran, Erika C. Espinosa, David C. Glahn, and John Blangero. "Highly efficient induced pluripotent stem cell reprogramming of cryopreserved lymphoblastoid cell lines." Journal of Biological Methods 7, no. 1 (January 8, 2020): 124. http://dx.doi.org/10.14440/jbm.2020.296.

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36

Zhu, Xiaorui, Xianping Tao, Tao Gu, and Jian Lu. "ReLog: A systematic approach for supporting efficient reprogramming in wireless sensor networks." Journal of Parallel and Distributed Computing 102 (April 2017): 132–48. http://dx.doi.org/10.1016/j.jpdc.2016.12.010.

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37

Yoo, Junsang, Yujung Chang, Hongwon Kim, Soonbong Baek, Hwan Choi, Gun-Jae Jeong, Jaein Shin, Hongnam Kim, Byung-Soo Kim, and Jongpil Kim. "Efficient Direct Lineage Reprogramming of Fibroblasts into Induced Cardiomyocytes Using Nanotopographical Cues." Journal of Biomedical Nanotechnology 13, no. 3 (March 1, 2017): 269–79. http://dx.doi.org/10.1166/jbn.2017.2347.

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38

Krontiris, Ioannis, and Tassos Dimitriou. "Scatter – secure code authentication for efficient reprogramming in wireless sensor networks." International Journal of Sensor Networks 10, no. 1/2 (2011): 14. http://dx.doi.org/10.1504/ijsnet.2011.040900.

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39

Dong, Wei, Chun Chen, Jiajun Bu, and Chao Huang. "Enabling efficient reprogramming through reduction of executable modules in networked embedded systems." Ad Hoc Networks 11, no. 1 (January 2013): 473–89. http://dx.doi.org/10.1016/j.adhoc.2012.07.007.

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40

Santhosh Kumar, S. V. N., Yogesh Palanichamy, M. Selvi, Sannasi Ganapathy, Arputharaj Kannan, and Sankar Pariserum Perumal. "Energy efficient secured K means based unequal fuzzy clustering algorithm for efficient reprogramming in wireless sensor networks." Wireless Networks 27, no. 6 (June 13, 2021): 3873–94. http://dx.doi.org/10.1007/s11276-021-02660-9.

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41

Mujica, Gabriel, and Jorge Portilla. "Distributed Reprogramming on the Edge: A New Collaborative Code Dissemination Strategy for IoT." Electronics 8, no. 3 (February 28, 2019): 267. http://dx.doi.org/10.3390/electronics8030267.

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The ongoing era of the Internet of Things is opening up new opportunities towards the integration and interoperation of heterogeneous technologies at different abstraction layers, going from the so-called Edge Computing up to the Cloud and IoT Data Analytics level. With this evolution process the issue of efficient remote reprogramming on the Edge and the Extreme Edge deployments is becoming accentuated, as the amount and diversity of embedded sensing platforms is getting larger. To take advantage of the participation of heterogeneous devices and their in-field dynamic collaboration, in this work a new distributed code dissemination strategy for Edge node reprogramming is proposed, so as to efficiently support the functional reconfiguration, optimization and updating of sensor devices. It combines a partial reprogramming engine integrated into a modular sensor node architecture, with a smart IoT wearable platform for implementing the field collaborative framework. Results show that the proposed solution outperforms other traditional centric dissemination strategies, particularly when expanding the network reprogramming diversity and scale, which is an increasingly common feature in the IoT device deployments and maintenance.
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42

Markov, Glenn J., Thach Mai, Surag Nair, Anna Shcherbina, Yu Xin Wang, David M. Burns, Anshul Kundaje, and Helen M. Blau. "AP-1 is a temporally regulated dual gatekeeper of reprogramming to pluripotency." Proceedings of the National Academy of Sciences 118, no. 23 (June 4, 2021): e2104841118. http://dx.doi.org/10.1073/pnas.2104841118.

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Somatic cell transcription factors are critical to maintaining cellular identity and constitute a barrier to human somatic cell reprogramming; yet a comprehensive understanding of the mechanism of action is lacking. To gain insight, we examined epigenome remodeling at the onset of human nuclear reprogramming by profiling human fibroblasts after fusion with murine embryonic stem cells (ESCs). By assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and chromatin immunoprecipitation sequencing we identified enrichment for the activator protein 1 (AP-1) transcription factor c-Jun at regions of early transient accessibility at fibroblast-specific enhancers. Expression of a dominant negative AP-1 mutant (dnAP-1) reduced accessibility and expression of fibroblast genes, overcoming the barrier to reprogramming. Remarkably, efficient reprogramming of human fibroblasts to induced pluripotent stem cells was achieved by transduction with vectors expressing SOX2, KLF4, and inducible dnAP-1, demonstrating that dnAP-1 can substitute for exogenous human OCT4. Mechanistically, we show that the AP-1 component c-Jun has two unexpected temporally distinct functions in human reprogramming: 1) to potentiate fibroblast enhancer accessibility and fibroblast-specific gene expression, and 2) to bind to and repress OCT4 as a complex with MBD3. Our findings highlight AP-1 as a previously unrecognized potent dual gatekeeper of the somatic cell state.
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Mollinari, Cristiana, and Daniela Merlo. "Direct Reprogramming of Somatic Cells to Neurons: Pros and Cons of Chemical Approach." Neurochemical Research 46, no. 6 (March 5, 2021): 1330–36. http://dx.doi.org/10.1007/s11064-021-03282-5.

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AbstractTranslating successful preclinical research in neurodegenerative diseases into clinical practice has been difficult. The preclinical disease models used for testing new drugs not always appear predictive of the effects of the agents in the human disease state. Human induced pluripotent stem cells, obtained by reprogramming of adult somatic cells, represent a powerful system to study the molecular mechanisms of the disease onset and pathogenesis. However, these cells require a long time to differentiate into functional neural cells and the resetting of epigenetic information during reprogramming, might miss the information imparted by age. On the contrary, the direct conversion of somatic cells to neuronal cells is much faster and more efficient, it is safer for cell therapy and allows to preserve the signatures of donors’ age. Direct reprogramming can be induced by lineage-specific transcription factors or chemical cocktails and represents a powerful tool for modeling neurological diseases and for regenerative medicine. In this Commentary we present and discuss strength and weakness of several strategies for the direct cellular reprogramming from somatic cells to generate human brain cells which maintain age‐related features. In particular, we describe and discuss chemical strategy for cellular reprogramming as it represents a valuable tool for many applications such as aged brain modeling, drug screening and personalized medicine.
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44

Fink, Kyle D., Julien Rossignol, Ming Lu, Xavier Lévêque, Travis D. Hulse, Andrew T. Crane, Veronique Nerriere-Daguin, et al. "Survival and Differentiation of Adenovirus-Generated Induced Pluripotent Stem Cells Transplanted into the Rat Striatum." Cell Transplantation 23, no. 11 (November 2014): 1407–23. http://dx.doi.org/10.3727/096368913x670958.

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Induced pluripotent stem cells (iPSCs) offer certain advantages over embryonic stem cells in cell replacement therapy for a variety of neurological disorders. However, reliable procedures, whereby transplanted iPSCs can survive and differentiate into functional neurons, without forming tumors, have yet to be devised. Currently, retroviral or lentiviral reprogramming methods are often used to reprogram somatic cells. Although the use of these viruses has proven to be effective, formation of tumors often results following in vivo transplantation, possibly due to the integration of the reprogramming genes. The goal of the current study was to develop a new approach, using an adenovirus for reprogramming cells, characterize the iPSCs in vitro, and test their safety, survivability, and ability to differentiate into region-appropriate neurons following transplantation into the rat brain. To this end, iPSCs were derived from bone marrow-derived mesenchymal stem cells and tail-tip fibroblasts using a single cassette lentivirus or a combination of adenoviruses. The reprogramming efficiency and levels of pluripotency were compared using immunocytochemistry, flow cytometry, and real-time polymerase chain reaction. Our data indicate that adenovirus-generated iPSCs from tail-tip fibroblasts are as efficient as the method we used for lentiviral reprogramming. All generated iPSCs were also capable of differentiating into neuronal-like cells in vitro. To test the in vivo survivability and the ability to differentiate into region-specific neurons in the absence of tumor formation, 400,000 of the iPSCs derived from tail-tip fibroblasts that were transfected with the adenovirus pair were transplanted into the striatum of adult, immune-competent rats. We observed that these iPSCs produced region-specific neuronal phenotypes, in the absence of tumor formation, at 90 days posttransplantation. These results suggest that adenovirus-generated iPSCs may provide a safe and viable means for neuronal replacement therapies.
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Jeong, Pil-Soo, Bo-Woong Sim, Soo-Hyun Park, Min Ju Kim, Hyo-Gu Kang, Tsevelmaa Nanjidsuren, Sanghoon Lee, Bong-Seok Song, Deog-Bon Koo, and Sun-Uk Kim. "Chaetocin Improves Pig Cloning Efficiency by Enhancing Epigenetic Reprogramming and Autophagic Activity." International Journal of Molecular Sciences 21, no. 14 (July 8, 2020): 4836. http://dx.doi.org/10.3390/ijms21144836.

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Efficient epigenetic reprogramming is crucial for the in vitro development of mammalian somatic cell nuclear transfer (SCNT) embryos. The aberrant levels of histone H3 lysine 9 trimethylation (H3K9me3) is an epigenetic barrier. In this study, we evaluated the effects of chaetocin, an H3K9me3-specific methyltransferase inhibitor, on the epigenetic reprogramming and developmental competence of porcine SCNT embryos. The SCNT embryos showed abnormal levels of H3K9me3 at the pronuclear, two-cell, and four-cell stages compared to in vitro fertilized embryos. Moreover, the expression levels of H3K9me3-specific methyltransferases (suv39h1 and suv39h2) and DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) were higher in SCNT embryos. Treatment with 0.5 nM chaetocin for 24 h after activation significantly increased the developmental competence of SCNT embryos in terms of the cleavage rate, blastocyst formation rate, hatching rate, cell number, expression of pluripotency-related genes, and cell survival rate. In particular, chaetocin enhanced epigenetic reprogramming by reducing the H3K9me3 and 5-methylcytosine levels and restoring the abnormal expression of H3K9me3-specific methyltransferases and DNA methyltransferases. Chaetocin induced autophagic activity, leading to a significant reduction in maternal mRNA levels in embryos at the pronuclear and two-cell stages. These findings revealed that chaetocin enhanced the developmental competence of porcine SCNT embryos by regulating epigenetic reprogramming and autophagic activity and so could be used to enhance the production of transgenic pigs for biomedical research.
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46

Frakolaki, Efseveia, Panagiota Kaimou, Maria Moraiti, Katerina Kalliampakou, Kalliopi Karampetsou, Eleni Dotsika, Panagiotis Liakos, et al. "The Role of Tissue Oxygen Tension in Dengue Virus Replication." Cells 7, no. 12 (December 1, 2018): 241. http://dx.doi.org/10.3390/cells7120241.

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Low oxygen tension exerts a profound effect on the replication of several DNA and RNA viruses. In vitro propagation of Dengue virus (DENV) has been conventionally studied under atmospheric oxygen levels despite that in vivo, the tissue microenvironment is hypoxic. Here, we compared the efficiency of DENV replication in liver cells, monocytes, and epithelial cells under hypoxic and normoxic conditions, investigated the ability of DENV to induce a hypoxia response and metabolic reprogramming and determined the underlying molecular mechanism. In DENV-infected cells, hypoxia had no effect on virus entry and RNA translation, but enhanced RNA replication. Overexpression and silencing approaches as well as chemical inhibition and energy substrate exchanging experiments showed that hypoxia-mediated enhancement of DENV replication depends on the activation of the key metabolic regulators hypoxia-inducible factors 1α/2α (HIF-1α/2α) and the serine/threonine kinase AKT. Enhanced RNA replication correlates directly with an increase in anaerobic glycolysis producing elevated ATP levels. Additionally, DENV activates HIF and anaerobic glycolysis markers. Finally, reactive oxygen species were shown to contribute, at least in part through HIF, both to the hypoxia-mediated increase of DENV replication and to virus-induced hypoxic reprogramming. These suggest that DENV manipulates hypoxia response and oxygen-dependent metabolic reprogramming for efficient viral replication.
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47

Suresh, Bharathi, Junwon Lee, Kye-Seong Kim, and Suresh Ramakrishna. "The Importance of Ubiquitination and Deubiquitination in Cellular Reprogramming." Stem Cells International 2016 (2016): 1–14. http://dx.doi.org/10.1155/2016/6705927.

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Ubiquitination of core stem cell transcription factors can directly affect stem cell maintenance and differentiation. Ubiquitination and deubiquitination must occur in a timely and well-coordinated manner to regulate the protein turnover of several stemness related proteins, resulting in optimal embryonic stem cell maintenance and differentiation. There are two switches: an E3 ubiquitin ligase enzyme that tags ubiquitin molecules to the target proteins for proteolysis and a second enzyme, the deubiquitinating enzyme (DUBs), that performs the opposite action, thereby preventing proteolysis. In order to maintain stemness and to allow for efficient differentiation, both ubiquitination and deubiquitination molecular switches must operate properly in a balanced manner. In this review, we have summarized the importance of the ubiquitination of core stem cell transcription factors, such as Oct3/4, c-Myc, Sox2, Klf4, Nanog, and LIN28, during cellular reprogramming. Furthermore, we emphasize the role of DUBs in regulating core stem cell transcriptional factors and their function in stem cell maintenance and differentiation. We also discuss the possibility of using DUBs, along with core transcription factors, to efficiently generate induced pluripotent stem cells. Our review provides a relatively new understanding regarding the importance of ubiquitination/deubiquitination of stem cell transcription factors for efficient cellular reprogramming.
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48

Roy, Bibhas, Luezhen Yuan, Yaelim Lee, Aradhana Bharti, Aninda Mitra, and G. V. Shivashankar. "Fibroblast rejuvenation by mechanical reprogramming and redifferentiation." Proceedings of the National Academy of Sciences 117, no. 19 (April 29, 2020): 10131–41. http://dx.doi.org/10.1073/pnas.1911497117.

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Over the course of the aging process, fibroblasts lose contractility, leading to reduced connective-tissue stiffness. A promising therapeutic avenue for functional rejuvenation of connective tissue is reprogrammed fibroblast replacement, although major hurdles still remain. Toward this, we recently demonstrated that the laterally confined growth of fibroblasts on micropatterned substrates induces stem-cell-like spheroids. In this study, we embedded these partially reprogrammed spheroids in collagen-I matrices of varying densities, mimicking different three-dimensional (3D) tissue constraints. In response to such matrix constraints, these spheroids regained their fibroblastic properties and sprouted to form 3D connective-tissue networks. Interestingly, we found that these differentiated fibroblasts exhibit reduced DNA damage, enhanced cytoskeletal gene expression, and actomyosin contractility. In addition, the rejuvenated fibroblasts show increased matrix protein (fibronectin and laminin) deposition and collagen remodeling compared to the parental fibroblast tissue network. Furthermore, we show that the partially reprogrammed cells have comparatively open chromatin compaction states and may be more poised to redifferentiate into contractile fibroblasts in 3D-collagen matrix. Collectively, our results highlight efficient fibroblast rejuvenation through laterally confined reprogramming, which has important implications in regenerative medicine.
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49

Anokye-Danso, Frederick, Chinmay M. Trivedi, Denise Juhr, Mudit Gupta, Zheng Cui, Ying Tian, Yuzhen Zhang, et al. "Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency." Cell Stem Cell 8, no. 4 (April 2011): 376–88. http://dx.doi.org/10.1016/j.stem.2011.03.001.

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50

Anokye-Danso, Frederick, Chinmay M. Trivedi, Denise Juhr, Mudit Gupta, Zheng Cui, Ying Tian, Yuzhen Zhang, et al. "Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency." Cell Stem Cell 11, no. 6 (December 2012): 853. http://dx.doi.org/10.1016/j.stem.2012.11.006.

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