BRBseq of human skin-derived precursor hepatic progenitor-like cells with varying polygenic risk score for hepatic fat content exposed in vitro to vehicle-matched control medium or triggers related to MASH

92 human skin-derived precursor (hSKP) cell lines, isolated from unique donors, were genotyped for the following SNPs that have been linked to metabolic dysfunction-associated steatotic liver disease (MASLD) onset and progression: PNPLA3 rs738409 C>G, TM6SF2 rs58542926 C>T, GCKR rs1260326 C>T and MBOAT7 rs641738 C>T. Based on carriage of these SNPs, the polygenic risk score for hepatic fat content (PRS-HFC) was calculated for each cell line and used for classification in either a low, intermediate or high risk category. From the low and high risk category, five cell lines were selected and differentiated to hepatic progenitor-like cells (hSKP-HPCs) before exposing the cells for 24 hours to either vehicle-matched control medium or a mixture of MASH-related triggers including sodium oleate, palmitic acid, fructose, lipopolysaccharide and tumour necrosis factor alpha. Total RNA was extracted from the cells and processed for bulk RNA barcoding and sequencing (BRBseq) as described by Alpern and colleagues (2019).