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

Anna Falk, Philipp Koch, Jaideep Kesavan, Yasuhiro Takashima, Julia Ladewig, Michael Alexander, Ole Wiskow, Jignesh Tailor, Matthew Trotter, Steven Pollard, Austin Smith, Oliver Brüstle

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)e29597
JournalPLoS ONE
Volume7
Issue number1
DOIs
Publication statusPublished - 17 Jan 2012

Keywords

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

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