※ をクリックすると外部の論文のサイトが開きます。
論文
- タイトル
- タイトル（英）
- Generation of Monosomy 21q Human <scp>iPS</scp> Cells by <scp>CRISPR</scp>/Cas9‐Mediated Interstitial Megabase Deletion
- 参照URL
- https://researchmap.jp/szktr/published_papers/49164681
- 著者
- 著者（英）
- Masaya Egawa,Narumi Uno,Rina Komazaki,Yusuke Ohkame,Kyotaro Yamazaki,Chihiro Yoshimatsu,Yuki Ishizu,Yusaku Okano,Hitomaru Miyamoto,Mitsuhiko Osaki,Teruhiko Suzuki,Kazuyoshi Hosomichi,Yasunori Aizawa,Yasuhiro Kazuki,Kazuma Tomizuka
- 担当区分
- 概要
- 概要（英）
- ABSTRACT Missing an entire chromosome or chromosome arm in normal diploid cells has a deleterious impact on cell viability, which may contribute to the development of specific birth defects. Nevertheless, the effects of chromosome loss in human cells have remained unexplored due to the lack of suitable model systems. Here, we developed an efficient, selection‐free approach to generate partial monosomy in human induced pluripotent stem cells (iPSCs). The introduction of Cas9 proteins and a pair of gRNAs induces over megabase‐sized interstitial chromosomal deletions. Using human chromosome 21 (HSA21) as a model, partial monosomy 21q (PM21q) iPSC lines with deletions ranging from 4.5 to 27.9 Mb were isolated. A 33.6 Mb deletion, encompassing all protein‐coding genes on 21q, was also achieved, establishing the first 21q monosomy human iPSC line. Transcriptome and proteome analyses revealed that the abundances of mRNA and protein encoded by the majority of genes in the monosomic regions are half of the diploid expression level, indicating an absence of dosage compensation. The ability to generate customized partial monosomy cell lines on an isogenic, karyotypically normal background should facilitate the gain of novel insights into the impact of chromosome loss on cellular fitness.
- 出版者・発行元
- 出版者・発行元（英）
- Wiley
- 誌名
- 誌名（英）
- Genes to Cells
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2024年11月24日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- 1356-9597
- DOI URL
- https://doi.org/10.1111/gtc.13184
- 共同研究・競争的資金等の研究課題
研究者
鈴木 輝彦
(スズキ テルヒコ)