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Stage-specific regulation of reprogramming to induced pluripotent stem cells by Wnt signaling and T cell factor proteins.

Abstract：

:Wnt signaling is intrinsic to mouse embryonic stem cell self-renewal. Therefore, it is surprising that reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is not strongly enhanced by Wnt signaling. Here, we demonstrate that active Wnt signaling inhibits the early stage of reprogramming to iPSCs, whereas it is required and even stimulating during the late stage. Mechanistically, this biphasic effect of Wnt signaling is accompanied by a change in the requirement of all four of its transcriptional effectors: T cell factor 1 (Tcf1), Lef1, Tcf3, and Tcf4. For example, Tcf3 and Tcf4 are stimulatory early but inhibitory late in the reprogramming process. Accordingly, ectopic expression of Tcf3 early in reprogramming combined with its loss of function late enables efficient reprogramming in the absence of ectopic Sox2. Together, our data indicate that the stepwise process of reprogramming to iPSCs is critically dependent on the stage-specific control and action of all four Tcfs and Wnt signaling.

journal_name

Cell Rep

journal_title

Cell reports

authors

Ho R,Papp B,Hoffman JA,Merrill BJ,Plath K

doi

10.1016/j.celrep.2013.05.015

subject

Has Abstract

pub_date

2013-06-27 00:00:00

pages

2113-26

issue

6

issn

2211-1247

pii

S2211-1247(13)00232-5

journal_volume

3

pub_type

杂志文章

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