Generation of JAG1 gene c.1615C > T heterozygous mutation human embryonic stem cell line (SDQLCHe001-A) using cytosine base editor

Yue Li; Zirui Wan; Bin Wang; Haiyan Zhang; Jingyun Guan; Xiaomeng Yang; Xiaohua Jin; Xu Ma; Yi Liu

doi:10.1016/j.scr.2023.103120

Generation of JAG1 gene c.1615C > T heterozygous mutation human embryonic stem cell line (SDQLCHe001-A) using cytosine base editor

Stem Cell Res. 2023 Aug:70:103120. doi: 10.1016/j.scr.2023.103120. Epub 2023 May 16.

Authors

Yue Li¹, Zirui Wan², Bin Wang¹, Haiyan Zhang¹, Jingyun Guan¹, Xiaomeng Yang¹, Xiaohua Jin³, Xu Ma⁴, Yi Liu⁵

Affiliations

¹ Pediatric Research Institute, Children's Hospital Affiliated to Shandong University, Ji'nan 250022, China.
² National Research Institute for Family Planning, Beijing 100081, China; Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; National Human Genetic Resources Center, Beijing 102206, China.
³ National Research Institute for Family Planning, Beijing 100081, China; Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; National Human Genetic Resources Center, Beijing 102206, China. Electronic address: [email protected].
⁴ National Research Institute for Family Planning, Beijing 100081, China; Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; National Human Genetic Resources Center, Beijing 102206, China. Electronic address: [email protected].
⁵ Pediatric Research Institute, Children's Hospital Affiliated to Shandong University, Ji'nan 250022, China. Electronic address: [email protected].

PMID: 37245339
DOI: 10.1016/j.scr.2023.103120

Abstract

Pathogenic variants in Jagged-1 (JAG1), which encodes the ligand of the Notch receptor, had been demonstrated to cause Alagille syndrome. However, there is no evidence to support any genotype-phenotype correlations. Here, we generated a gene-edited human embryonic stem cell (hESC) line (H9) carrying the c.1615C > T mutation in JAG1 that was identified in a patient with Alagille syndrome (ALGS). This modified cell line was accomplished by using cytosine base editor (CBE), and may serve as a valuable model for JAG1 mutaion related disease, and facilitate to gain more insight into the biological function of JAG1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alagille Syndrome* / genetics
Alagille Syndrome* / metabolism
Alagille Syndrome* / pathology
Cell Line
Human Embryonic Stem Cells* / metabolism
Humans
Jagged-1 Protein / genetics
Jagged-1 Protein / metabolism
Mutation / genetics
Phenotype

Substances

Jagged-1 Protein
JAG1 protein, human