The transcription factor E2A drives neural differentiation in pluripotent cells

• Published in: Development (Cambridge) Vol. 147; no. 12
• Main Authors: Rao, Chandrika, Malaguti, Mattias, Mason, John O, Lowell, Sally
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 22.06.2020
• Subjects: 3' Untranslated Regions; Animals; Basic Helix-Loop-Helix Transcription Factors - deficiency; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cell Differentiation; Cell Lineage; Cell Self Renewal; CRISPR-Cas Systems - genetics; Dimerization; Mice; Mouse Embryonic Stem Cells - cytology; Mouse Embryonic Stem Cells - metabolism; Neurons - cytology; Neurons - metabolism; Octamer Transcription Factor-3 - deficiency; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; RNA, Guide, CRISPR-Cas Systems; SOXB1 Transcription Factors - deficiency; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Stem Cells and Regeneration; Transcriptome; Up-Regulation; Pluripotent; E2A; BHLH; Neural development
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.184093

The intrinsic mechanisms that link extracellular signalling to the onset of neural differentiation are not well understood. In pluripotent mouse cells, BMP blocks entry into the neural lineage via transcriptional upregulation of inhibitor of differentiation (Id) factors. We have previously identified the major binding partner of Id proteins in pluripotent cells as the basic helix-loop-helix (bHLH) transcription factor (TF) E2A. Id1 can prevent E2A from forming heterodimers with bHLH TFs or from forming homodimers. Here, we show that overexpression of a forced E2A homodimer is sufficient to drive robust neural commitment in pluripotent cells, even under non-permissive conditions. Conversely, we find that E2A null cells display a defect in their neural differentiation capacity. E2A acts as an upstream activator of neural lineage genes, including and , and as a repressor of Nodal signalling. Our results suggest a crucial role for E2A in establishing neural lineage commitment in pluripotent cells.