Erk signaling suppresses embryonic stem cell self-renewal to specify endoderm

TY - JOUR

T1 - Erk signaling suppresses embryonic stem cell self-renewal to specify endoderm

AU - Hamilton, William B

AU - Brickman, Joshua M

N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2014/12/24

Y1 - 2014/12/24

N2 - Fgf signaling via Erk activation has been associated with both neural induction and the generation of a primed state for the differentiation of embryonic stem cells (ESCs) to all somatic lineages. To dissect the role of Erk in both ESC self-renewal and lineage specification, we explored the requirements for this pathway in various in vitro differentiation settings. A combination of pharmacological inhibition of Erk signaling and genetic loss of function reveal a role for Erk signaling in endodermal, but not neural differentiation. Neural differentiation occurs normally despite a complete block to Erk phosphorylation. In support of this, Erk activation in ESCs derepresses primitive endoderm (PrE) gene expression as a consequence of inhibiting the pluripotent/epiblast network. The early response to Erk activation correlates with functional PrE priming, whereas sustained Erk activity results in PrE differentiation. Taken together, our results suggest that Erk signaling suppresses pluripotent gene expression to enable endodermal differentiation.

AB - Fgf signaling via Erk activation has been associated with both neural induction and the generation of a primed state for the differentiation of embryonic stem cells (ESCs) to all somatic lineages. To dissect the role of Erk in both ESC self-renewal and lineage specification, we explored the requirements for this pathway in various in vitro differentiation settings. A combination of pharmacological inhibition of Erk signaling and genetic loss of function reveal a role for Erk signaling in endodermal, but not neural differentiation. Neural differentiation occurs normally despite a complete block to Erk phosphorylation. In support of this, Erk activation in ESCs derepresses primitive endoderm (PrE) gene expression as a consequence of inhibiting the pluripotent/epiblast network. The early response to Erk activation correlates with functional PrE priming, whereas sustained Erk activity results in PrE differentiation. Taken together, our results suggest that Erk signaling suppresses pluripotent gene expression to enable endodermal differentiation.

U2 - 10.1016/j.celrep.2014.11.032

DO - 10.1016/j.celrep.2014.11.032

M3 - Journal article

C2 - 25533345

SN - 2211-1247

VL - 9

SP - 2056

EP - 2070

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -