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

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Peteri , U-K , Pitkonen , J , Utami , K H , Paavola , J , Roybon , L , Pouladi , M A & Castren , M L 2021 , ' Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity ' , Brain Sciences , vol. 11 , no. 2 , 209 . https://doi.org/10.3390/brainsci11020209

Title: Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity
Author: Peteri, Ulla-Kaisa; Pitkonen, Juho; Utami, Kagistia Hana; Paavola, Jere; Roybon, Laurent; Pouladi, Mahmoud A.; Castren, Maija L.
Other contributor: University of Helsinki, NeuroDevDiseaseModelling
University of Helsinki, Department of Physiology
University of Helsinki, Department of Physiology




Date: 2021-02
Language: eng
Number of pages: 14
Belongs to series: Brain Sciences
ISSN: 2076-3425
DOI: https://doi.org/10.3390/brainsci11020209
URI: http://hdl.handle.net/10138/329039
Abstract: Astrocytes form functionally and morphologically distinct populations of cells with brainregion-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 beta. 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.
Subject: pluripotent stem cells
differentiation
astrocytes
patterning
fragile X syndrome
3112 Neurosciences
3124 Neurology and psychiatry
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