BioProject

Skin fibroblasts from individuals with PBD-ZSD, a rare autosomal recessive disorder caused by peroxisome assembly defects, show defects in lipid metabolism that provide the basis for clinical diagnostic tests, but are not among the cell types most affected by disease. More...

Skin fibroblasts from individuals with PBD-ZSD, a rare autosomal recessive disorder caused by peroxisome assembly defects, show defects in lipid metabolism that provide the basis for clinical diagnostic tests, but are not among the cell types most affected by disease. To explore phenotypes of more clinically relevant cell types, skin fibroblasts from PBD-ZSD patients and healthy controls were reprogrammed into iPS cells with all the hallmark properties of pluripotency. Subsequently, iPSCs were differentiated into ASGPR-positive hepatocyte-like cells that were subject to flow cytometry and subject to gene expression profiling. We report the gene expression profiles of hepatocyte-like cells derived from iPSCs that were themselves derived from skin fibroblasts from PBD-ZSD patient donors and healthy controls. Overall design: The overall goal was to evaluate gene expression biomarkers of hepatocyte-like cells derived from PBD-ZSD patients and healthy controls. Dermal fibroblast cultures from 2 PBD-ZSD patients and 1 healthy control were reprogrammed into iPSCs by transfection with retroviruses designed to express the human OCT4, SOX2, KLF4 and c-MYC cDNA (see GEO entry GSE43996). Hepatic cell lineages were derived following the protocol of Duan (Duan Y, Catana A, Meng Y, Yamamoto N, He S, Gupta S et al. Stem Cells. 2007;25:3058-68; Duan Y, Ma X, Zou W, Wang C, Bahbahan IS, Ahuja TP et al. Stem Cells. 2010;28:674-86) with modifications. Total RNA samples from flow-sorted ASGPR-positive candidate hepatocyte-like cells obtained from healthy (control1) and PBD-ZSD patient (PBD_PEX1ms1 and PBD_PEX1fs1) donors were processed and analyzed on Affymetrix Human Genome 133A 2.0 microarrays. Less...