Heterogeneity of glial progenitor cells during the neurogenesis-to-gliogenesis switch in the developing human cerebral cortex

Cell Rep. 2021 Mar 2;34(9):108788. doi: 10.1016/j.celrep.2021.108788.

Abstract

The heterogeneity and molecular characteristics of progenitor cells, especially glial progenitors, in the developing human cerebral cortex remain elusive. Here, we find that EGFR expression begins to sharply increase after gestational week (GW) 20, which corresponds to the beginning stages of human gliogenesis. In addition, EGFR+ cells are mainly distributed in the germinal zone and frequently colocalize with the stemness marker SOX2 during this period. Then, by performing single-cell RNA sequencing on these EGFR+ cells, we successfully enriched and characterized various glial- and neuronal-lineage progenitor cells and validated their phenotypes in fixed slices. Notably, we identified two subgroups with molecular characteristics similar to those of astrocytes, and the immunostaining results show that these cells are mainly distributed in the outer subventricular zone and might originate from the outer radial glial cells. In short, the EGFR-sorting strategy and molecular signatures in the diverse lineages provide insights into human glial development.

Keywords: EGFR-expressing cells; astrocyte progenitor cells; glial cells; human cerebral cortex development; neuronal progenitor cells; oligodendrocyte progenitor cells; single-cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Lineage*
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology*
  • Databases, Genetic
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Humans
  • Mice
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / physiology*
  • Neurogenesis*
  • Neuroglia / metabolism
  • Neuroglia / physiology*
  • Neurons / metabolism
  • Neurons / physiology*
  • Oligodendrocyte Transcription Factor 2 / genetics
  • Oligodendrocyte Transcription Factor 2 / metabolism
  • Phenotype
  • RNA-Seq
  • Single-Cell Analysis
  • Transcription, Genetic

Substances

  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • SPARCL1 protein, human
  • EGFR protein, human
  • ErbB Receptors