RNA-seq of hepatocytes obtained through step-wise differentiation of hIPSCs from a patient with A1AT deficiency and its point mutation-corrected isogenic hIPSC line. Comparison to primary hepatocytes from a healthy donor and an A1AT-deficient patient.

A1AT deficiency is an autosomal not recessive disorder caused by mutations in the SERPINA1 gene. Individuals with the Z variant retain polymerised protein in the endoplasmic reticulum of hepatocytes, predisposing them to liver disease. This study primarily aimed to uncover the molecular mechanisms that link protein misfolding to liver injury. To that end, RNA was extracted from hepatocytes differentiated from hIPSCs carrying the Z variant and mutation-corrected hIPSCs (control). The second objective of the study was to benchmark the gene expression profile of both hIPSC-derived hepatocytes types to primary hepatocytes of wild type and a Z variant A1AT genotype.