Modeling of Alpha-1 Antitrypsin Deficiency with Syngeneic Human iPSC-Hepatocytes Reveals Metabolic Dysfunction and Cellular Heterogeneity in PiMZ and PiZZ Hepatic Cells (bulk RNA-Seq)

We profiled the global transcriptomes of PiZZ6 syngenenic ZZ, MZ, and MM iPSCs that underwent directed differentiation to the hepatic lineage using RNA sequencing. Overall design: Total RNA was extracted and then mRNA isolated using magnetic bead based poly(A) selection followed by synthesis of cDNA fragments. These were then end paired, and PCR amplified to create each cDNA library and sequenced on the NextSeq 500. Reads were then eliagned to ENSEMBL human reference genome GRCh38.91 using STAR. The Bioconductor package edgeR was used to normalize count matrix, followed by the limma and voom packages for linear model fitting and differential expression testing.