Systems Analyses Reveal Shared and Diverse Attributes of Oct4 Regulation in Pluripotent Cells

TY - JOUR

T1 - Systems Analyses Reveal Shared and Diverse Attributes of Oct4 Regulation in Pluripotent Cells

AU - Ding, Li

AU - Paszkowski-Rogacz, Maciej

AU - Winzi, Maria

AU - Chakraborty, Debojyoti

AU - Theis, Mirko

AU - Singh, Sukhdeep

AU - Ciotta, Giovanni

AU - Poser, Ina

AU - Roguev, Assen

AU - Chu, Wai Kit

AU - Choudhary, Chuna Ram

AU - Mann, Matthias

AU - Stewart, A Francis

AU - Krogan, Nevan

AU - Buchholz, Frank

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/8/26

Y1 - 2015/8/26

N2 - Summary We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization, and "protein-level dependency" studies - a systematic technique that uncovers post-transcriptional regulation - to delineate the network of factors that control the expression of Oct4, a key regulator of pluripotency. Our data signify that there are similarities, but also fundamental differences in Oct4 regulation in EpiSCs versus embryonic stem cells (ESCs). Through multiparametric data analyses, we predict that Tox4 is associating with the Paf1C complex, which maintains cell identity in both cell types, and validate that this protein-protein interaction exists in ESCs and EpiSCs. We also identify numerous knockdowns that increase Oct4 expression in EpiSCs, indicating that, in stark contrast to ESCs, Oct4 is under active repressive control in EpiSCs. These studies provide a framework for better understanding pluripotency and for dissecting the molecular events that govern the transition from the pre-implantation to the post-implantation state.

AB - Summary We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization, and "protein-level dependency" studies - a systematic technique that uncovers post-transcriptional regulation - to delineate the network of factors that control the expression of Oct4, a key regulator of pluripotency. Our data signify that there are similarities, but also fundamental differences in Oct4 regulation in EpiSCs versus embryonic stem cells (ESCs). Through multiparametric data analyses, we predict that Tox4 is associating with the Paf1C complex, which maintains cell identity in both cell types, and validate that this protein-protein interaction exists in ESCs and EpiSCs. We also identify numerous knockdowns that increase Oct4 expression in EpiSCs, indicating that, in stark contrast to ESCs, Oct4 is under active repressive control in EpiSCs. These studies provide a framework for better understanding pluripotency and for dissecting the molecular events that govern the transition from the pre-implantation to the post-implantation state.

U2 - 10.1016/j.cels.2015.08.002

DO - 10.1016/j.cels.2015.08.002

M3 - Journal article

C2 - 27135800

SN - 2405-4712

VL - 1

SP - 141

EP - 151

JO - Cell Systems

JF - Cell Systems

IS - 2

ER -