Generation of iPSC line ERCi004-A from human dermal fibroblasts of a patient with maturity-onset diabetes of the young type 3 caused by a heterozygous mutation in the HNF1A gene

Abstract

Maturity-onset diabetes of the young type 3 (MODY3) disorder is characterized by an autosomal dominant type of inheritance and highly heterogeneous clinical phenotype influenced by type and position of mutation in the HNF1A gene. We reprogrammed dermal fibroblasts derived from a patient with MODY3 carrying a heterozygous mutation in the site encoding the transactivation domain of the HNF1A protein (c. 864delGinsCC, p.Gly292ArgfsTer25) into iPSCs using transfection with self-replicating RNA vector. Obtained iPSCs (ERCi004-A line) proliferate in dense monolayer cell colonies, have a normal karyotype (46,XX), express pluripotency markers (OCT4, SOX2, TRA-1-60). The functional pluripotency of iPSCs was confirmed by their ability to form embryoid bodies and differentiate into the three germ layers (ecto-, endo-, and mesoderm). Sanger sequencing of iPSCs confirmed the presence of pathogenic heterozygous mutation in the HNF1A gene. This cell line could be useful to modeling of MODY3 pathology to improve understanding of the mechanism of the transactivation domain mutation, as well as a potential source for autologous cell-based therapy.