Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons

PLoS One. 2012;7(1):e29597. doi: 10.1371/journal.pone.0029597. Epub 2012 Jan 17.

Abstract

Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) provide new prospects for studying human neurodevelopment and modeling neurological disease. In particular, iPSC-derived neural cells permit a direct comparison of disease-relevant molecular pathways in neurons and glia derived from patients and healthy individuals. A prerequisite for such comparative studies are robust protocols that efficiently yield standardized populations of neural cell types. Here we show that long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) derived from 3 hESC and 6 iPSC lines in two independent laboratories exhibit consistent characteristics including i) continuous expandability in the presence of FGF2 and EGF; ii) stable neuronal and glial differentiation competence; iii) characteristic transcription factor profile; iv) hindbrain specification amenable to regional patterning; v) capacity to generate functionally mature human neurons. We further show that lt-NES cells are developmentally distinct from fetal tissue-derived radial glia-like stem cells. We propose that lt-NES cells provide an interesting tool for studying human neurodevelopment and may serve as a standard system to facilitate comparative analyses of hESC and hiPSC-derived neural cells from control and diseased genetic backgrounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cluster Analysis
  • Epidermal Growth Factor / pharmacology
  • Fibroblast Growth Factor 2 / pharmacology
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neuroepithelial Cells / cytology*
  • Neuroepithelial Cells / metabolism
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neurons / cytology*
  • Neurons / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Transcription Factors
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor