Specification of Transplantable Astroglial Subtypes From Human Pluripotent Stem Cells

Nat Biotechnol. 2011 May 22;29(6):528-34. doi: 10.1038/nbt.1877.

Abstract

Human pluripotent stem cells (hPSCs) have been differentiated efficiently to neuronal cell types. However, directed differentiation of hPSCs to astrocytes and astroglial subtypes remains elusive. In this study, hPSCs were directed to nearly uniform populations of immature astrocytes (>90% S100β(+) and GFAP(+)) in large quantities. The immature human astrocytes exhibit similar gene expression patterns as primary astrocytes, display functional properties such as glutamate uptake and promotion of synaptogenesis, and become mature astrocytes by forming connections with blood vessels after transplantation into the mouse brain. Furthermore, hPSC-derived neuroepithelia, patterned to rostral-caudal and dorsal-ventral identities with the same morphogens used for neuronal subtype specification, generate immature astrocytes that express distinct homeodomain transcription factors and display phenotypic differences of different astroglial subtypes. These human astroglial progenitors and immature astrocytes will be useful for studying astrocytes in brain development and function, understanding the roles of astrocytes in disease processes and developing novel treatments for neurological disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / cytology*
  • Astrocytes / transplantation*
  • Blotting, Western
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Developmental
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutamic Acid / analysis
  • Glutamic Acid / pharmacokinetics
  • Humans
  • Immunochemistry
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / transplantation*
  • Mice
  • Neural Stem Cells / metabolism
  • Neuroepithelial Cells / cytology
  • Neuroepithelial Cells / transplantation
  • Neurogenesis
  • Pregnancy
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • Transcription Factors
  • Glutamic Acid