Origins and Proliferative States of Human Oligodendrocyte Precursor Cells

Wei Huang, Aparna Bhaduri, Dmitry Velmeshev, Shaohui Wang, Li Wang, Catherine A. Rottkamp, Arturo Alvarez-Buylla, David H. Rowitch, Arnold R. Kriegstein

Research output: Contribution to journalArticle

Abstract

Human cerebral cortex size and complexity has increased greatly during evolution. While increased progenitor diversity and enhanced proliferative potential play important roles in human neurogenesis and gray matter expansion, the mechanisms of human oligodendrogenesis and white matter expansion remain largely unknown. Here, we identify EGFR-expressing “Pre-OPCs” that originate from outer radial glial cells (oRGs) and undergo mitotic somal translocation (MST) during division. oRG-derived Pre-OPCs provide an additional source of human cortical oligodendrocyte precursor cells (OPCs) and define a lineage trajectory. We further show that human OPCs undergo consecutive symmetric divisions to exponentially increase the progenitor pool size. Additionally, we find that the OPC-enriched gene, PCDH15, mediates daughter cell repulsion and facilitates proliferation. These findings indicate properties of OPC derivation, proliferation, and dispersion important for human white matter expansion and myelination.

Original languageEnglish (US)
Pages (from-to)594-608.e11
JournalCell
Volume182
Issue number3
DOIs
StatePublished - Aug 6 2020
Externally publishedYes

Keywords

  • cortical expansion
  • EGFR
  • oligodendrogenesis
  • OPC
  • PCDH15
  • self-repulsion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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