2021年12月
A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome
Communications Biology
- 巻
- 4
- 号
- 1
- 開始ページ
- 730
- 終了ページ
- 730
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s42003-021-02242-7
- 出版者・発行元
- Springer Science and Business Media LLC
<title>Abstract</title>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 <italic>XIST</italic>-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 <italic>XIST</italic> 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 <italic>DYRK1A</italic> and <italic>PIGP</italic> on DS APCs. Our collection of human isogenic cell lines provides a comprehensive set of cellular models for further DS investigations.
- リンク情報
- ID情報
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- DOI : 10.1038/s42003-021-02242-7
- eISSN : 2399-3642
- PubMed ID : 34127780
- PubMed Central 記事ID : PMC8203796