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.

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

Genes to Cells

GENES TO CELLS 为发表描述分子和细胞生物学重要方面的论文提供了一个国际论坛。该杂志旨在发表在相关领域提供概念性进展的论文。将特别强调旨在了解生物学事件的基本机制的工作。

Genes to Cells is an international forum dedicated to publishing important research papers in the field of molecular and cellular biology. The journal aims to present conceptual advancements in related areas, with a particular emphasis on studies that seek to understand the fundamental mechanisms underlying biological events.

《Genes to Cells》是一个国际论坛，专注于发表分子和细胞生物学领域的重要研究论文。该杂志旨在发布在相关领域内提供概念性进展的研究成果，特别强调揭示生物学事件基本机制的研究工作。

Generation of Monosomy 21q Human <scp>iPS</scp> Cells by <scp>CRISPR</scp>/Cas9‐Mediated Interstitial Megabase Deletion

通过CRISPR/Cas9介导的中间兆碱基缺失生成21q单体人类iPS细胞

Category	Quartile
生物学	4
生物学, 细胞生物学	4
生物学, 遗传学	4

Generation of Monosomy 21q Human iPS Cells by CRISPR/Cas9‐Mediated Interstitial Megabase Deletion

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Journal Info

Category	Quartile
GENETICS & HEREDITY	4