The NIPBL-gene mutation of a Cornelia de Lange Syndrome patient causes deficits in the hepatocyte differentiation of induced Pluripotent Stem Cells via altered chromatin-accessibility.

ABSTRACT: The Cornelia de Lange syndrome (CdLS) is a rare genetic disease, which is characterized by a cohesinopathy. Mutations of the NIPBL gene are observed in 65% of CdLS patients. A novel iPSC (induced Pluripotent Stem Cell) line was reprogrammed from the leukocytes of a CdLS patient carrying a missense mutation of the NIPBL gene. A mutation-corrected isogenic iPSC-line and two iPSC-lines generated from the healthy parents were used as controls. The iPSC lines were differentiated along the hepatocyte-lineage. Comparative immunofluorescence, RNA-seq and ATAC-seq analyses were performed on undifferentiated and differentiated iPSCs. In addition, chromatin organization was studied by ChIP-Seq analysis on the patient derived iPSCs as well as the respective controls. Relative to the mutation-corrected

SUBMITTER: Foglia M 

PROVIDER: S-EPMC11511806 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature