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 - 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 - 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
VL - 1
SP - 141
EP - 151
JO - Cell Systems
JF - Cell Systems
SN - 2405-4712
IS - 2
ER -