Mechanisms and models of somatic cell reprogramming
Nature Reviews GeneticsPublished 17 May 2013Open access
Yosef Buganim, Dina A. Faddah, Rudolf Jaenisch
Citations449
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TL;DR
Recent discoveries regarding the role of reprogramming factors in remodelling the genome are discussed, including new insights into the function of MYC, and the different phases, markers and emerging models ofReprogramming are described.
Abstract
Conversion of somatic cells to pluripotency by defined factors is a long and complex process that yields embryonic-stem-cell-like cells that vary in their developmental potential. To improve the quality of resulting induced pluripotent stem cells (iPSCs), which is important for potential therapeutic applications, and to address fundamental questions about control of cell identity, molecular mechanisms of the reprogramming process must be understood. Here we discuss recent discoveries regarding the role of reprogramming factors in remodelling the genome, including new insights into the function of MYC, and describe the different phases, markers and emerging models of reprogramming.
Keywords
Biochemistry, Genetics and Molecular Biology
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Journal of Biological ChemistryMicroRNA Cluster 302–367 Enhances Somatic Cell Reprogramming by Accelerating a Mesenchymal-to-Epithelial Transition
274 Citations2011Baojian Liao, Xichen Bao +16 more
This work has successfully delivered entire miRNA clusters into reprogramming fibroblasts using retroviral vectors and adds new evidence for the emerging relationship between pluripotency and the epithelial phenotype.
Nature MethodsProteomic and phosphoproteomic comparison of human ES and iPS cells
266 Citations2011Douglas H. Phanstiel, Justin Brumbaugh +11 more
Deep proteomic coverage of four human embryonic stem cell and four induced pluripotent stem cell lines in biological triplicate is reported and the Stem Cell–Omics Repository is introduced, a resource to collate and display quantitative information across multiple planes of measurement, including mRNA, protein and post-translational modifications.
Cell ReportsHighly Coordinated Proteome Dynamics during Reprogramming of Somatic Cells to Pluripotency
250 Citations2012Jenny Hansson, Mahmoud Reza Rafiee +7 more
It is demonstrated that the nucleoporin Nup210 is essential for reprogramming by its permitting of rapid cellular proliferation and subsequent progression through MET, and this study provides a rich resource toward an enhanced mechanistic understanding of cellular reprograming.
Cell stem cellLow Incidence of DNA Sequence Variation in Human Induced Pluripotent Stem Cells Generated by Nonintegrating Plasmid Expression
242 Citations2012Linzhao Cheng, Nancy F. Hansen +13 more
The whole-genome sequencing of three human iPSC lines derived from two cell types of an adult donor by episomal vectors suggests that episome-mediated reprogramming is not inherently mutagenic during integration-free iPSCs induction.
Proceedings of the National Academy of SciencesES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable
224 Citations2006Tobias Brambrink, Konrad Hochedlinger +2 more
The findings support the notion that ES cell lines derived from cloned or fertilized blastocysts have an identical therapeutic potential, and indicate that NT-ES cell derivation rigorously selects for those immortal cells that have erased the "epigenetic memory" of the donor nucleus and, thus, become functionally equivalent.
Journal of Biological Chemistryc-Myc Mediates Activation of the cad Promoter via a Post-RNA Polymerase II Recruitment Mechanism
223 Citations2001Scott R. Eberhardy, Peggy Farnham
The results suggest that c-Myc activates transcription of cad by stimulating promoter clearance and elongation, perhaps via recruitment of P-TEFb.
Cell stem cellLab-Specific Gene Expression Signatures in Pluripotent Stem Cells
218 Citations2010Aaron M. Newman, James B. Cooper
Using an unsupervised clustering algorithm, a strong correlation between gene expression signatures and specific laboratories in both embryonic stem cell and induced-pluripotent stem cell lines is revealed, consistent with the hypothesis that in vitro microenvironmental context differentially impacts the gene expression signs of both iPSCs and ESCs.
Cell ResearchEmbryonic stem cell and induced pluripotent stem cell: an epigenetic perspective
217 Citations2012Gaoyang Liang, Yi Zhang
Accumulating evidence indicates that epigenetic mechanisms not only play important roles in the iPSC generation process, but also affect the properties of reprogrammed iPSCs.
PLoS ONEMitochondrial Rejuvenation After Induced Pluripotency
216 Citations2010Steven T. Suhr, Elizabeth Chang +7 more
Results suggest that IPSC conversion not only resets the “biological clock”, but can also rejuvenate the energetic capacity of derived cells.
The EMBO JournalMyc‐induced proliferation and transformation require Akt‐mediated phosphorylation of FoxO proteins
210 Citations2004Caroline Bouchard, Judith Marquardt +3 more
This work shows that Myc recruits TFIIH, P‐TEFb and Mediator to the cyclin D2 and other target promoters, while the PI3‐kinase pathway controls formation of the preinitiation complex and loading of RNA polymerase II.
Nature BiotechnologyDynamic single-cell imaging of direct reprogramming reveals an early specifying event
205 Citations2010Zachary D. Smith, Iftach Nachman +2 more
High-resolution, time-lapse imaging is used to trace the reprogramming process over 2 weeks from single mouse embryonic fibroblasts to pluripotency factor–positive colonies and reveals that successfully reprograming cells undergo a rapid shift in their proliferative rate that coincides with a reduction in cellular area.
Molecular CellMolecular Roadblocks for Cellular Reprogramming
194 Citations2012Thomas Vierbuchen, Marius Wernig
How transcription factors interface with the genome and induce changes in cellular identity in the context of development and reprogramming is discussed.
ScienceiPSC Disease Modeling
178 Citations2012Frank Soldner, Rudolf Jaenisch
Limitations ofuced pluripotent stem cell technology are described, and some solutions for ensuring that iPSC technology lives up to at least some of its promise are presented.
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