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Generation of the human pluripotent stem-cell-derived astrocyte model with forebrain identity

Peteri, Ulla Kaisa LU ; Pitkonen, Juho ; Utami, Kagistia Hana ; Paavola, Jere ; Roybon, Laurent LU ; Pouladi, Mahmoud A. and Castrén, Maija L. (2021) In Brain Sciences 11(2).
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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Astrocytes, Differentiation, Fragile X syndrome, Patterning, Pluripotent stem cells
in
Brain Sciences
volume
11
issue
2
article number
209
pages
14 pages
publisher
MDPI AG
external identifiers
  • pmid:33572154
  • scopus:85101049356
ISSN
2076-3425
DOI
10.3390/brainsci11020209
language
English
LU publication?
yes
id
b0d77bff-8ea2-4b43-b7c9-0fb3c8bfc057
date added to LUP
2021-03-02 08:56:33
date last changed
2025-03-07 09:59:34
@article{b0d77bff-8ea2-4b43-b7c9-0fb3c8bfc057,
  abstract     = {{<p>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.</p>}},
  author       = {{Peteri, Ulla Kaisa and Pitkonen, Juho and Utami, Kagistia Hana and Paavola, Jere and Roybon, Laurent and Pouladi, Mahmoud A. and Castrén, Maija L.}},
  issn         = {{2076-3425}},
  keywords     = {{Astrocytes; Differentiation; Fragile X syndrome; Patterning; Pluripotent stem cells}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{MDPI AG}},
  series       = {{Brain Sciences}},
  title        = {{Generation of the human pluripotent stem-cell-derived astrocyte model with forebrain identity}},
  url          = {{http://dx.doi.org/10.3390/brainsci11020209}},
  doi          = {{10.3390/brainsci11020209}},
  volume       = {{11}},
  year         = {{2021}},
}