携带纯合JAG1缺失的人诱导多能干细胞系的产生。

Generation of human induced pluripotent stem cell lines carrying homozygous JAG1 deletions.

作者信息

Song Dan, Zheng Yun-Wen, Hemmi Yasuko, An Yuri, Noguchi Michiya, Nakamura Yukio, Oda Tatsuya, Hayashi Yohei

机构信息

iPS Cell Advanced Characterization and Development Team, BioResource Research Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan; Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, and School of Biotechnology and Heath Sciences, Wuyi University, Jiangmen, Guangdong 529020, China; Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, kanazawa-Ku, Yokohama, Kanagawa 234-0006, Japan.

出版信息

Stem Cell Res. 2021 Dec;57:102588. doi: 10.1016/j.scr.2021.102588. Epub 2021 Oct 26.

DOI:10.1016/j.scr.2021.102588

PMID:34736037

Abstract

JAG1gene encodes Jagged1 protein, which is a ligand for NOTCH receptors. JAG1 mutations cause Alagille syndrome, in which liver failure occurs caused by abnormalities in the bile ducts. In this study, we generated two homozygous JAG1 knockout iPSC lines (JAG1KO iPSC) by creating indels with CRISPR-Cas9 technology. These newly generated JAG1KO iPSC lines showed similar self-renewal and pluripotency as their original iPSC WTC11 line. These iPSC lines carried deletions around the translation start codon of JAG1 gene, causing compromised Jagged1 protein expression. These JAG1KO iPSC lines are promising bioresources to studyJagged1 function in human development and pathology.

摘要

JAG1基因编码锯齿状蛋白1，它是NOTCH受体的一种配体。JAG1突变会导致阿拉吉耶综合征，该病中胆管异常会引发肝衰竭。在本研究中，我们利用CRISPR-Cas9技术产生插入缺失，从而构建了两个纯合的JAG1基因敲除诱导多能干细胞系（JAG1KO iPSC）。这些新产生的JAG1KO iPSC系与其原始的iPSC WTC11系表现出相似的自我更新能力和多能性。这些iPSC系在JAG1基因翻译起始密码子周围存在缺失，导致锯齿状蛋白1的表达受损。这些JAG1KO iPSC系是研究锯齿状蛋白1在人类发育和病理学中功能的有前景的生物资源。