Abstract：
:Cellular reprogramming converts differentiated cells into induced pluripotent stem cells (iPSCs). However, this process is typically very inefficient, complicating mechanistic studies. We identified and molecularly characterized rare, early intermediates poised to reprogram with up to 95% efficiency, without perturbing additional genes or pathways, during iPSC generation from mouse embryonic fibroblasts. Analysis of these cells uncovered transcription factors (e.g., Tfap2c and Bex2) that are important for reprogramming but dispensable for pluripotency maintenance. Additionally, we observed striking patterns of chromatin hyperaccessibility at pluripotency loci, which preceded gene expression in poised intermediates. Finally, inspection of these hyperaccessible regions revealed an early wave of DNA demethylation that is uncoupled from de novo methylation of somatic regions late in reprogramming. Our study underscores the importance of investigating rare intermediates poised to produce iPSCs, provides insights into reprogramming mechanisms, and offers a valuable resource for the dissection of transcriptional and epigenetic dynamics intrinsic to cell fate change.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Schwarz BA,Cetinbas M,Clement K,Walsh RM,Cheloufi S,Gu H,Langkabel J,Kamiya A,Schorle H,Meissner A,Sadreyev RI,Hochedlinger Kdoi
10.1016/j.stem.2018.06.013subject
Has Abstractpub_date
2018-08-02 00:00:00pages
289-305.e5issue
2eissn
1934-5909issn
1875-9777pii
S1934-5909(18)30295-9journal_volume
23pub_type
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