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

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

Nature

1] Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain [2] Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain [3] Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg Lluis Companys 23, 08010 Barcelona, Spain.

Published: February 2014

AI Article Synopsis

  • * The process involves a dramatic rise in the expression of pluripotency and epithelial-mesenchymal transition genes, with 60% of the cells exhibiting Oct4 expression within 2 days.
  • * C/EBPα makes chromatin accessible for pluripotency genes and activates the enzyme Tet2, which is crucial for both B-cell transdifferentiation and iPS reprogramming, highlighting

Article Abstract

CCAAT/enhancer binding protein-α (C/EBPα) induces transdifferentiation of B cells into macrophages at high efficiencies and enhances reprogramming into induced pluripotent stem (iPS) cells when co-expressed with the transcription factors Oct4 (Pou5f1), Sox2, Klf4 and Myc (hereafter called OSKM). However, how C/EBPα accomplishes these effects is unclear. Here we find that in mouse primary B cells transient C/EBPα expression followed by OSKM activation induces a 100-fold increase in iPS cell reprogramming efficiency, involving 95% of the population. During this conversion, pluripotency and epithelial-mesenchymal transition genes become markedly upregulated, and 60% of the cells express Oct4 within 2 days. C/EBPα acts as a 'path-breaker' as it transiently makes the chromatin of pluripotency genes more accessible to DNase I. C/EBPα also induces the expression of the dioxygenase Tet2 and promotes its translocation to the nucleus where it binds to regulatory regions of pluripotency genes that become demethylated after OSKM induction. In line with these findings, overexpression of Tet2 enhances OSKM-induced B-cell reprogramming. Because the enzyme is also required for efficient C/EBPα-induced immune cell conversion, our data indicate that Tet2 provides a mechanistic link between iPS cell reprogramming and B-cell transdifferentiation. The rapid iPS reprogramming approach described here should help to fully elucidate the process and has potential clinical applications.

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Source
http://dx.doi.org/10.1038/nature12885DOI Listing

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