PRC2 Acts as a Critical Timer That Drives Oligodendrocyte Fate over Astrocyte Identity by Repressing the Notch Pathway

Wenxian Wang, Hyeyoung Cho, Dongkyeong Kim, Younjung Park, Ji Hwan Moon, Su Jeong Lim, Sung Min Yoon, Michael McCane, Sue A. Aicher, Sangsoo Kim, Ben Emery, Jae W. Lee, Seunghee Lee, Yungki Park, Soo Kyung Lee

Research output: Contribution to journalArticle

Abstract

PRC2 creates the repressive mark histone H3 Lys27 trimethylation. Although PRC2 is involved in various biological processes, its role in glial development remains ambiguous. Here, we show that PRC2 is required for oligodendrocyte (OL) differentiation and myelination, but not for OL precursor formation. PRC2-deficient OL lineage cells differentiate into OL precursors, but they fail to trigger the molecular program for myelination, highlighting that PRC2 is essential for directing the differentiation timing of OL precursors. PRC2 null OL lineage cells aberrantly induce Notch pathway genes and acquire astrocytic features. The repression of the Notch pathway restores the myelination program and inhibits abnormal astrocytic differentiation in the PRC2-deficient OL lineage, indicating that Notch is a major target of PRC2. Altogether, our studies propose a specific action of PRC2 as a novel gatekeeper that determines the glial fate choice and the timing of OL lineage progression and myelination by impinging on the Notch pathway.

Original languageEnglish (US)
Article number108147
JournalCell Reports
Volume32
Issue number11
DOIs
StatePublished - Sep 15 2020

Keywords

  • EED
  • Ezh2
  • H3K27me3
  • NFIA
  • Notch pathway
  • PRC2
  • Wnt pathway
  • astrocyte
  • myelination
  • oligodendrocyte

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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