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


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 S100?. 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.

SUBMITTER: Peteri UK 

PROVIDER: S-EPMC7914711 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Peteri Ulla-Kaisa UK   Pitkonen Juho J   Utami Kagistia Hana KH   Paavola Jere J   Roybon Laurent L   Pouladi Mahmoud A MA   Castrén Maija L ML  

Brain sciences 20210209 2


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  ...[more]

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