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

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

doi:10.1016/j.scr.2021.102588

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

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

Authors

Dan Song¹, Yun-Wen Zheng², Yasuko Hemmi³, Yuri An³, Michiya Noguchi⁴, Yukio Nakamura⁴, Tatsuya Oda⁵, Yohei Hayashi⁶

Affiliations

¹ 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.
² 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.
³ iPS Cell Advanced Characterization and Development Team, BioResource Research Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
⁴ Cell Engineering Division, BioResource Research Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
⁵ Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.
⁶ iPS Cell Advanced Characterization and Development Team, BioResource Research Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan. Electronic address: yohei.hayashi@riken.jp.

PMID: 34736037
DOI: 10.1016/j.scr.2021.102588

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.