The key to pluripotency cracked? Gene directing cellular reprogramming found

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Hot on the heels of last week’s European Court of Justice’s provisional announcement, in favor of California’s company Stem Cell International, that it may be possible to patent some pluripotent stem cells – those derived from unfertilized human eggs in this case – comes another remarkable announcement from the pluripotent stem cell community. A group of scientists led by Joseph Cibelli at Michigan State Univeristy reported, in the journal Science by studying cellular transcriptional regulatory networks, of having discovered a key factor directing differentiation of human adult dermal fibroblasts into undifferentiated iPSCs.

Up until now, one concern with identifying such iPSC reprogramming factors was that many of them might be expressed at relatively low levels undetectable to microarray-based analysis.  The factor, a histone-remodeling chaperone named ASF1A, in tandem with the OCT4 gene, was identified as being responsible for cellular reprogramming, after the authors analyzed more than 5,000 oocyte genes. ASF1A is part of a group of candidate oocyte reprogramming factors (CORFs) that are believed to regulate cell fate, alongside ARID2, ASF1B, DPPA3, ING3, MSL3, H1FOO, and KDM6B. OCT4 had previously been described as one of the key transciption factors regulating pluripotency.

Genomic approaches to understand pluripotency have been the subject of ongoing research for a considerable amount of time. The assumption that pluripotency states of embryonic stem cells and induced pluripotent stem cells are in fact different was just recently confirmed (see last week’s blog entry), but up until now the exact genetic cues that are directly responsible for pluripotency had not been identified.

The Science paper is the culmination of multiple years of investigation and represents a significant milestone on the path to understanding the subcellular mechanisms regulating pluripotency.



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