A Multi-omics Integrative Analysis Based on CRISPR Screens Re-defines the Pluripotency Regulatory Network in ESCs

Overview

Journal Commun Biol

Specialty Biology

Date 2023 Apr 14

PMID 37059858

Authors

Yan Ruan

Jiaqi Wang

Meng Yu

Fengsheng Wang

Jiangjun Wang

Yixiao Xu

Lianlian Liu

Yuda Cheng

Ran Yang

Chen Zhang

Yi Yang

Jiali Wang

Wei Wu

Yi Huang

Yanping Tian

Guangxing Chen

Junlei Zhang

Rui Jian

Affiliations

Soon will be listed here.

Abstract

A comprehensive and precise definition of the pluripotency gene regulatory network (PGRN) is crucial for clarifying the regulatory mechanisms in embryonic stem cells (ESCs). Here, after a CRISPR/Cas9-based functional genomics screen and integrative analysis with other functional genomes, transcriptomes, proteomes and epigenome data, an expanded pluripotency-associated gene set is obtained, and a new PGRN with nine sub-classes is constructed. By integrating the DNA binding, epigenetic modification, chromatin conformation, and RNA expression profiles, the PGRN is resolved to six functionally independent transcriptional modules (CORE, MYC, PAF, PRC, PCGF and TBX). Spatiotemporal transcriptomics reveal activated CORE/MYC/PAF module activity and repressed PRC/PCGF/TBX module activity in both mouse ESCs (mESCs) and pluripotent cells of early embryos. Moreover, this module activity pattern is found to be shared by human ESCs (hESCs) and cancers. Thus, our results provide novel insights into elucidating the molecular basis of ESC pluripotency.

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