Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate Into Functionally Integrated Neurons in the Neonatal Cortex

Cell Stem Cell. 2017 Mar 2;20(3):360-373.e7. doi: 10.1016/j.stem.2016.10.020. Epub 2016 Nov 23.

Abstract

Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2+ neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex.

Keywords: PDGFRβ; electrophysiology; lineage tracing; meninges; neonatal cerebral cortex; neural progenitors; neurogenesis; radial glia cells; single-cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation*
  • Cell Lineage
  • Cell Movement*
  • Cerebral Cortex / cytology*
  • Embryo, Mammalian / cytology
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Gene Expression Profiling
  • HEK293 Cells
  • Humans
  • Meninges / cytology*
  • Mice, Inbred C57BL
  • Nestin / metabolism
  • Neurogenesis*
  • Neuroglia / cytology*
  • Neurons / cytology*
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Reproducibility of Results
  • Single-Cell Analysis
  • Spheroids, Cellular / cytology
  • Staining and Labeling
  • Transcriptome / genetics

Substances

  • Excitatory Amino Acid Transporter 1
  • Nestin
  • Slc1a3 protein, mouse
  • Receptor, Platelet-Derived Growth Factor beta