Lucky iPSCs

摘要

The probabilistic behavior of direct induction of pluripotency has been a subject of intense research interest. Here we discuss recently published reports on this topic. Induced pluripotent stem cells (iPSCs) can be generated from somatic cells by ectopic expression of different pluripotency-promoting transcription factors, canonically Oct4, Sox2, Klf4 and Myc (abbreviated as OSKM) [1]. Exogenous elements involved in signaling and chromatin modification, such as inhibition of ERK and GSK3 signaling (known as ‘2i’ conditions), Lif/Stat3 signaling and/or inclusion of ascorbic acid-containing supplements, directly participate in the reactivation of the endogenous pluripotency circuitry by OSKM [2]. However, OSKM reprogramming is a relatively inefficient process in which only a small minority of somatic donor cells become reprogrammed after an initial period of 10 to 14 days (0.1% to 15% efficiency) [3]. A number of recent studies have sought to better understand the nature of this inefficiency, and how it might be overcome [4-6].