FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes

Sci Rep. 2019 Jul 3;9(1):9610. doi: 10.1038/s41598-019-46110-1.


The glutamate transporter 1 (GLT1) is upregulated during astrocyte development and maturation in vivo and is vital for astrocyte function. Yet it is expressed at low levels by most cultured astrocytes. We previously showed that maturation of human and mouse stem cell-derived astrocytes - including functional glutamate uptake - could be enhanced by fibroblast growth factor (FGF)1 or FGF2. Here, we examined the specificity and mechanism of action of FGF2 and other FGF family members, as well as neurotrophic and differentiation factors, on mouse embryonic stem cell-derived astrocytes. We found that some FGFs - including FGF2, strongly increased GLT1 expression and enhanced astrocyte proliferation, while others (FGF16 and FGF18) mainly affected maturation. Interestingly, BMP4 increased astrocytic GFAP expression, and BMP4-treated astrocytes failed to promote the survival of motor neurons in vitro. Whole transcriptome analysis showed that FGF2 treatment regulated multiple genes linked to cell division, and that the mRNA encoding GLT1 was one of the most strongly upregulated of all astrocyte canonical markers. Since GLT1 is expressed at reduced levels in many neurodegenerative diseases, activation of this pathway is of potential therapeutic interest. Furthermore, treatment with FGFs provides a robust means for expansion of functionally mature stem cell-derived astrocytes for preclinical investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Computational Biology / methods
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / pharmacology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Ontology
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / drug effects
  • Mouse Embryonic Stem Cells / metabolism
  • Multigene Family
  • Stem Cells / cytology*


  • Glucose Transporter Type 1
  • Fibroblast Growth Factors