Generation of human induced pluripotent stem cell lines derived from patients of cystic biliary atresia.

Abstract

Biliary atresia (BA), resulting from abnormal development of the liver's internal or external bile ducts, can lead to liver damage and potentially fatal cirrhosis. Type I cystic biliary atresia is a relatively uncommon, but clinically significant variant of BA. It is critical to develop experimental models of BA to examine the etiology and pathogenesis, which remain elusive, and to develop future therapeutics. Here, we have successfully generated a panel of human induced pluripotent stem cells (hiPSCs) from five Japanese patients carrying type I cystic BA. These hiPSC lines exhibited characteristics of self-renewal and pluripotency. These cells held normal karyotypes mostly, but one of them carried hemizygous deletions, the clinical significance of which is unknown yet. Whole genome sequence analysis indicated that some of the mutations or single nucleotide polymorphisms (SNPs) commonly found in these patients are related to hepatobiliary abnormality. Given the limited understanding of the molecular pathogenesis of cystic BA, attributed to unknown factors of genetic and environmental causes, these cellular resources will be instrumental in replicating disease phenotypes and in advancing novel therapies for this disease.