A chemical logic for reprogramming to pluripotency
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摘要:
The defining characteristics of pluripotent stem cells (PSCs) — selfrenewal and the potential to differentiate into any cell type — herald promise for use in regenerative medicine.By leveraging the knowledge that embryonic stem cells (ESCs) have reprogramming capacity,Takahashi and Yamanaka [1] identified the minimal set of transcription factors-the now-famous quartet of Oct4,Sox2,Klf4 and c-Myc — required to confer the developmental potential of an ES cell onto a terminally differentiated somatic cell to generate induced PSCs (iPSCs).The development of non-integrative methods to generate human iPSCs has reduced risks emanating from residual expression of transgenes [2].However,efficient iPSC generation still relies on the transient delivery of transgenes that in other contexts are oncogenic.Therefore,it is theoretically appealing to envision that complete replacement of gene transfer with small-molecule compounds might improve the safety of human iPSCs.