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

Ekaterina Savchenko, Gabriel N. Teku, Antonio Boza-Serrano, Kaspar Russ, Manon Berns, Tomas Deierborg, Nuno J. Lamas, Hynek Wichterle, Jeffrey D Rothstein, Christopher E. Henderson, Mauno Vihinen, Laurent Roybon

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Number of pages1
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Jul 3 2019

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Fibroblast Growth Factors
Astrocytes
Stem Cells
Amino Acid Transport System X-AG
Fibroblast Growth Factor 2
Fibroblast Growth Factor 1
Nerve Growth Factors
Motor Neurons
Gene Expression Profiling
Neurodegenerative Diseases
Cell Division
Glutamic Acid
Messenger RNA

ASJC Scopus subject areas

  • General

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Savchenko, E., Teku, G. N., Boza-Serrano, A., Russ, K., Berns, M., Deierborg, T., ... Roybon, L. (2019). FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes. Scientific reports, 9(1). https://doi.org/10.1038/s41598-019-46110-1

FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes. / Savchenko, Ekaterina; Teku, Gabriel N.; Boza-Serrano, Antonio; Russ, Kaspar; Berns, Manon; Deierborg, Tomas; Lamas, Nuno J.; Wichterle, Hynek; Rothstein, Jeffrey D; Henderson, Christopher E.; Vihinen, Mauno; Roybon, Laurent.

In: Scientific reports, Vol. 9, No. 1, 03.07.2019.

Research output: Contribution to journalArticle

Savchenko, E, Teku, GN, Boza-Serrano, A, Russ, K, Berns, M, Deierborg, T, Lamas, NJ, Wichterle, H, Rothstein, JD, Henderson, CE, Vihinen, M & Roybon, L 2019, 'FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes', Scientific reports, vol. 9, no. 1. https://doi.org/10.1038/s41598-019-46110-1
Savchenko, Ekaterina ; Teku, Gabriel N. ; Boza-Serrano, Antonio ; Russ, Kaspar ; Berns, Manon ; Deierborg, Tomas ; Lamas, Nuno J. ; Wichterle, Hynek ; Rothstein, Jeffrey D ; Henderson, Christopher E. ; Vihinen, Mauno ; Roybon, Laurent. / FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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