Origins and Proliferative States of Human Oligodendrocyte Precursor Cells

Cell. 2020 Aug 6;182(3):594-608.e11. doi: 10.1016/j.cell.2020.06.027. Epub 2020 Jul 16.

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.

Keywords: EGFR; OPC; PCDH15; cortical expansion; oligodendrogenesis; self-repulsion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherin Related Proteins
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism
  • Ependymoglial Cells / cytology
  • Ependymoglial Cells / metabolism*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Neurogenesis / genetics*
  • Oligodendrocyte Precursor Cells / cytology
  • Oligodendrocyte Precursor Cells / metabolism*
  • RNA, Small Interfering
  • RNA-Seq
  • Single-Cell Analysis
  • White Matter / cytology
  • White Matter / embryology
  • White Matter / metabolism

Substances

  • CDHR15, human
  • Cadherin Related Proteins
  • Cadherins
  • RNA, Small Interfering
  • EGFR protein, human
  • ErbB Receptors