Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors

Nat Commun. 2015 Mar 23:6:6500. doi: 10.1038/ncomms7500.

Abstract

Decoding heterogeneity of pluripotent stem cell (PSC)-derived neural progeny is fundamental for revealing the origin of diverse progenitors, for defining their lineages, and for identifying fate determinants driving transition through distinct potencies. Here we have prospectively isolated consecutively appearing PSC-derived primary progenitors based on their Notch activation state. We first isolate early neuroepithelial cells and show their broad Notch-dependent developmental and proliferative potential. Neuroepithelial cells further yield successive Notch-dependent functional primary progenitors, from early and midneurogenic radial glia and their derived basal progenitors, to gliogenic radial glia and adult-like neural progenitors, together recapitulating hallmarks of neural stem cell (NSC) ontogeny. Gene expression profiling reveals dynamic stage-specific transcriptional patterns that may link development of distinct progenitor identities through Notch activation. Our observations provide a platform for characterization and manipulation of distinct progenitor cell types amenable for developing streamlined neural lineage specification paradigms for modelling development in health and disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • Cell Line
  • Cerebral Cortex / embryology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Humans
  • Microscopy, Confocal
  • Neural Plate / embryology
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neuroglia / cytology
  • Neuroglia / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Notch / metabolism*

Substances

  • RNA, Messenger
  • Receptors, Notch

Associated data

  • GEO/GSE65369