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Cited by 34Down syndrome and intellectual disability researchPluripotent Stem Cells ResearchNeurogenesis and neuroplasticity mechanisms

A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome

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Kawatani, Keiji, Nambara, Toshihiko, Nawa, Nobutoshi, Yoshimatsu, Hidetaka, Kusakabe, Haruna, Hirata, Katsuya, Tanave, Akira, Sumiyama, Kenta +5 more·2021·Communications Biology
DOI 10.1038/s42003-021-02242-7PMC PMC8203796

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Abstract

Astrocytes exert adverse effects on the brains of individuals with Down syndrome (DS). Although a neurogenic-to-gliogenic shift in the fate-specification step has been reported, the mechanisms and key regulators underlying the accelerated proliferation of astrocyte precursor cells (APCs) in DS remain elusive. Here, we established a human isogenic cell line panel based on DS-specific induced pluripotent stem cells, the XIST -mediated transcriptional silencing system in trisomic chromosome 21, and genome/chromosome-editing technologies to eliminate phenotypic fluctuations caused by genetic variation. The transcriptional responses of genes observed upon XIST induction and/or downregulation are not uniform, and only a small subset of genes show a characteristic expression pattern, which is consistent with the proliferative phenotypes of DS APCs. Comparative analysis and experimental verification using gene modification reveal dose-dependent proliferation-promoting activity of DYRK1A and PIGP on DS APCs. Our collection of human isogenic cell lines provides a comprehensive set of cellular models for further DS investigations.

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  • Increased astrogliogenesis can be partially reversed by silencing HSA21 by the non-coding RNA XIST in induced pluripotent stem cell-derived astrocyte progenitor cells.

    “This increased astrogliogenesis can be partially reversed by the silencing of HSA21 by the non-coding RNA XIST in iPSC-derived astrocyte progenitor cells104,105.”

    From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [104]

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Authors
Kawatani, K., Nambara, T., Nawa, N., Yoshimatsu, H., Kusakabe, H., Hirata, K., Tanave, A., Sumiyama, K., Banno, K., Taniguchi, H., Arahori, H., Ozono, K., & Kitabatake, Y.
Affiliations
  • The University of Osaka (JP)
  • Osaka Women's and Children's Hospital (JP)
  • RIKEN Center for Biosystems Dynamics Research (JP)
  • Nara Medical University (JP)
Corresponding author
Kitabatake, Yasuji
ORCID
Venue
Communications Biology
Publisher
Springer Science and Business Media LLC
Published
2021-06-14
Volume
4
Issue
1
Pages
730-730
ISSN
2399-3642 (ISSN-L)
DOI
10.1038/s42003-021-02242-7
PMC
PMC8203796
OpenAlex
W3169004320
Cited by
34
References
9
Citations by year
2026: 4 · 2025: 10 · 2024: 9 · 2023: 4 · 2022: 5 · 2021: 2
FWCI
4.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Biology (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Japan Agency for Medical Research and Development (JP19bm0804009)
  • MEXT | Japan Society for the Promotion of Science (JP16K10090, JP19H03619, JP17K16257)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
Down syndrome, astrocyte proliferation, induced pluripotent stem cells, isogenic cell lines, DYRK1A
MeSH terms
Gene Editing, Astrocytes, Cell Line, Down Syndrome, Humans, Infant, Newborn, Male, Blotting, Western, In Situ Hybridization, Fluorescence, Gene Dosage, Gene Silencing, Cell Proliferation, Induced Pluripotent Stem Cells

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