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Brain Sciences
Volume 11
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10.3390/brainsci11020209
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Article

Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity

by
Ulla-Kaisa Peteri
1,
Juho Pitkonen
1,
Kagistia Hana Utami
2,
Jere Paavola
3,
Laurent Roybon
4,5,
Mahmoud A. Pouladi
2 and
Maija L. Castrén
1,*
1
Faculty of Medicine, Department of Physiology, University of Helsinki, P.O. Box 63, FI-00290 Helsinki, Finland
2
Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore (A*STAR), 8A Biomedical Grove, Immunos, Level 5, Singapore 138648, Singapore
3
Minerva Foundation Institute for Medical Research, Biomedicum 2U, Tukholmankatu 8, FI-00290 Helsinki, Finland
4
Stem Cell Laboratory for CNS Disease Modeling, Department of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden
5
MultiPark and the Lund Stem Cell Center, Lund University, SE-221 84 Lund, Sweden
*
Author to whom correspondence should be addressed.
Brain Sci. 2021, 11(2), 209; https://doi.org/10.3390/brainsci11020209
Submission received: 13 January 2021 / Revised: 4 February 2021 / Accepted: 6 February 2021 / Published: 9 February 2021
(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)
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Abstract

Astrocytes form functionally and morphologically distinct populations of cells with brain-region-specific properties. Human pluripotent stem cells (hPSCs) offer possibilities to generate astroglia for studies investigating mechanisms governing the emergence of astrocytic diversity. We established a method to generate human astrocytes from hPSCs with forebrain patterning and final specification with ciliary neurotrophic factor (CNTF). Transcriptome profiling and gene enrichment analysis monitored the sequential expression of genes determining astrocyte differentiation and confirmed activation of forebrain differentiation pathways at Day 30 (D30) and D60 of differentiation in vitro. More than 90% of astrocytes aged D95 in vitro co-expressed the astrocytic markers glial fibrillary acidic protein (GFAP) and S100β. Intracellular calcium responses to ATP indicated differentiation of the functional astrocyte population with constitutive monocyte chemoattractant protein-1 (MCP-1/CCL2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) expression. The method was reproducible across several hPSC lines, and the data demonstrated the usefulness of forebrain astrocyte modeling in research investigating forebrain pathology.
Keywords: pluripotent stem cells; differentiation; astrocytes; patterning; fragile X syndrome pluripotent stem cells; differentiation; astrocytes; patterning; fragile X syndrome
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MDPI and ACS Style

Peteri, U.-K.; Pitkonen, J.; Utami, K.H.; Paavola, J.; Roybon, L.; Pouladi, M.A.; Castrén, M.L. Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity. Brain Sci. 2021, 11, 209. https://doi.org/10.3390/brainsci11020209

AMA Style

Peteri U-K, Pitkonen J, Utami KH, Paavola J, Roybon L, Pouladi MA, Castrén ML. Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity. Brain Sciences. 2021; 11(2):209. https://doi.org/10.3390/brainsci11020209

Chicago/Turabian Style

Peteri, Ulla-Kaisa, Juho Pitkonen, Kagistia Hana Utami, Jere Paavola, Laurent Roybon, Mahmoud A. Pouladi, and Maija L. Castrén. 2021. "Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity" Brain Sciences 11, no. 2: 209. https://doi.org/10.3390/brainsci11020209

APA Style

Peteri, U.-K., Pitkonen, J., Utami, K. H., Paavola, J., Roybon, L., Pouladi, M. A., & Castrén, M. L. (2021). Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity. Brain Sciences, 11(2), 209. https://doi.org/10.3390/brainsci11020209

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