Myc represses primitive endoderm differentiation in pluripotent stem cells.

Abstract:

:The generation of induced pluripotent stem cells (iPSCs) provides a novel method to facilitate investigations into the mechanisms that control stem cell pluripotency and self-renewal. Myc has previously been shown to be critical for murine embryonic stem cell (mESC) maintenance, while also enhancing directed reprogramming of fibroblasts by effecting widespread changes in gene expression. Despite several studies identifying in vivo target genes, the precise mechanism by which Myc regulates pluripotency remains unknown. Here we report that codeletion of c- and N-MYC in iPSCs and ESCs results in their spontaneous differentiation to primitive endoderm. We show that Myc sustains pluripotency through repression of the primitive endoderm master regulator GATA6, while also contributing to cell cycle control by regulation of the mir-17-92 miRNA cluster. Our findings demonstrate the indispensable requirement for c- or N-myc in pluripotency beyond proliferative and metabolic control.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Smith KN,Singh AM,Dalton S

doi

10.1016/j.stem.2010.06.023

subject

Has Abstract

pub_date

2010-09-03 00:00:00

pages

343-54

issue

3

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(10)00350-4

journal_volume

7

pub_type

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