C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells

Stefano, Bruno Di; Sardina, Jose Luis; Oevelen, Chris van; Collombet, Samuel; Kallin, Eric M.; Vicent, Guillermo P.; Lü, Jun; Thieffry, Denis; Beato, Miguel; Graf, Thomas

doi:10.1038/nature12885

Cited by 190 publications

(226 citation statements)

References 124 publications

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“…Together, these findings support the notion that sphere formation induces MET. We hypothesize that this transition may be conducive to iPS cell generation through a sequential EMT-MET mechanism as described previously [27,28].…”

Section: Figmentioning

confidence: 99%

Sphere Formation Permits Oct4 Reprogramming of Ciliary Body Epithelial Cells into Induced Pluripotent Stem Cells

Chavala

2014

Stem Cells and Development

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Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by defined sets of transcription factors. We previously described reprogramming of monolayer-cultured adult mouse ciliary body epithelial (CE) cells by Oct4 and Klf4, but not with Oct4 alone. In this study, we report that Oct4 alone is sufficient to reprogram CE cells to iPS cells through sphere formation. Furthermore, we demonstrate that sphere formation induces a partial reprogramming state characterized by expression of retinal progenitor markers, upregulation of reprogramming transcription factors, such as Sall4 and Nanog, demethylation in the promoter regions of pluripotency associated genes, and mesenchymal to epithelial transition. The Oct4-iPS cells maintained normal karyotypes, expressed markers for pluripotent stem cells, and were capable of differentiating into derivatives of all three embryonic germ layers in vivo and in vitro. These findings suggest that sphere formation may render somatic cells more susceptible to reprogramming.

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Section: Figmentioning

confidence: 99%

Sphere Formation Permits Oct4 Reprogramming of Ciliary Body Epithelial Cells into Induced Pluripotent Stem Cells

Chavala

2014

Stem Cells and Development

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“…Reprogramming by exogenous factors is nowadays considered as a multistep process in which cells must overcome a series of roadblocks to ultimately acquire pluripotency [3,4], though under certain conditions it can also be deterministic [5][6][7]. Two fundamental reprogramming roadblocks are the activation of a p53-mediated response that promotes apoptosis and cell senescence, and the inefficient removal of preexisting somatic-like epigenetic marks.…”

Section: Introductionmentioning

confidence: 99%

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

et al. 2014

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Recent studies have boosted our understanding of long noncoding RNAs (lncRNAs) in numerous biological processes, but few have examined their roles in somatic cell reprogramming. Through expression profiling and functional screening, we have identified that the large intergenic noncoding RNA p21 (lincRNA-p21) impairs reprogramming. Notably, lincRNA-p21 is induced by p53 but does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase SETDB1 and the maintenance DNA methyltransferase DNMT1, which is facilitated by the RNA-binding protein HNRNPK. Consequently, lincRNA-p21 prevents reprogramming by sustaining H3K9me3 and/or CpG methylation at pluripotency gene promoters. Our results provide insight into the role of lncRNAs in reprogramming and establish a novel link between p53 and heterochromatin regulation.

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“…The utilization of specific ''path-breaker'' proteins such as CCAAT/ enhancer-binding protein alpha (C/EBPa) make the chromatin more accessible and thus significantly speed up and improve the efficiency of epigenetic reprogramming [55]. Furthermore, depletion of the Mbd3/nucleosome remodeling and deacetylation (NuRD) repressor complex allows for epigenetic reprogramming as a deterministic process with high efficiency [56].…”

Section: Epigenetic Reprogrammingmentioning

confidence: 99%

“…There have been recent studies that attempt to reduce the tumorigenicity of hIPSCs [160,161]. The efficiency of the reprogramming process is another important hurdle for hPSC translation, although there has been recent progress on this front [55,56,[162][163][164].…”

Section: Safety Concerns and Current Barriers For Hpsc Clinical Transmentioning

confidence: 99%

Human Stem Cells for Craniomaxillofacial Reconstruction

Jalali

Kirkpatrick

Cameron

et al. 2014

Stem Cells and Development

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C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells

Cited by 190 publications

References 124 publications

Sphere Formation Permits Oct4 Reprogramming of Ciliary Body Epithelial Cells into Induced Pluripotent Stem Cells

Sphere Formation Permits Oct4 Reprogramming of Ciliary Body Epithelial Cells into Induced Pluripotent Stem Cells

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

Human Stem Cells for Craniomaxillofacial Reconstruction

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