Two new induced pluripotent stem cell (iPSC) lines that carry homozygous JAG1 deletions have been generated by Japanese researchers. 

These cell lines will not only be a valuable resource to better understand the functions of the Jagged1 protein in the NOTCH signal pathways, but they will also be useful in disease modeling of Alagille syndrome, which is mainly caused by mutations in the JAG1 gene.

The team led by Yohei Hayashi, PhD, from RIKEN BioResource Research Center in Tsukuba, Japan called the stem cell lines JAG1KO_IIA5 for UCSFi001-A-58 and JAG1KO_IIIB4 for UCSFi001-A-59. They published this laboratory resource in the journal Stem Cell Research.

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Read more about Alagille syndrome etiology

The researchers used the CRISPR-Cas9 technology to create indels to generate the 2 JAG1 knockout cell lines. Using TA cloning and Sanger sequencing, they showed that the cell lines carry deletions around the translation start codon of the JAG1 gene.

The cell lines compromised Jagged1 protein expression as shown by Western blot analysis. 

Finally, they expressed comparable levels of self-renewal genes like OCT3/4, NANOG, SOX2, and KLF4 as their parental line and can form embryoid bodies, suggesting that they have similar self-renewal and pluripotency as their original line.

“These JAG1KO iPSC lines are promising bioresources to study Jagged1 function in human development and pathology,” the authors wrote.

Jagged 1 is the ligand of the NOTCH2 receptor. The NOTCH signaling pathway plays a crucial role during embryonic development. The binding of Jagged 1 to the NOTCH receptor is thought to be involved in cell fate during hematopoiesis and in early and late-stage cardiovascular development and angiogenesis.

More than 90% of cases of Alagille syndrome cases are caused by mutations in the JAG1 gene with the rest being caused by mutations in the NOTCH2 gene.


Song D, Zheng YW, Hemmia Y, et al. Generation of human induced pluripotent stem cell lines carrying homozygous JAG1 deletions. Stem Cell Res. 2021;57:102588. doi:10.1016/j.scr.2021.102588