Open AccessE2A regulates neural ectoderm fate specification in human embryonic stem cells
Author(s) -
Siqi Yi,
Xiaotian Huang,
Shan Zhou,
Yuan Zhou,
Michael Anderson,
Juan Carlos ZúñigaPflücker,
Qingxian Luan,
Yang Li
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.190298
Subject(s) - biology , ectoderm , embryonic stem cell , microbiology and biotechnology , neural stem cell , stem cell , neural development , embryogenesis , developmental biology , embryo , neuroscience , anatomy , genetics , gene
E proteins transcription factors are critical for many cell fate decisions. However, the roles of E proteins in the germ-layer specification of human embryonic stem cells (hESC) are poorly understood. We disrupted the TCF3 gene locus to delete the E protein E2A in hESCs. E2A KO hESCs retained key features of pluripotency, but displayed decreased neural ectoderm coupled with enhanced mesoendoderm outcomes. Genome-wide analyses showed that E2A directly regulates neural ectoderm and Nodal pathway genes. Accordingly, inhibition of Nodal or E2A overexpression partially rescued the neural ectoderm defect in E2A KO hESCs. Loss of E2A had little impact on the epigenetic landscape of hESCs, whereas E2A KO neural precursors displayed increased accessibility of the gene locus encoding the Nodal agonist CRIPTO. Double-deletion of both E2A and HEB (TCF12) resulted in a more severe neural ectoderm defect. Therefore, this study reveals critical context-dependent functions for E2A in human neural ectoderm fate-specification.