Single cell RNA sequencing of AATD iPSC-derived hepatocytes following Z mutation correction by base-editing

We performed single cell transcriptomic profiling of cells derived from induced human pluripotent stem cells (iPSCs) using hepatocyte directed differentiation protocol which derived iHeps. We used the alpha-1 antitrypsin deficiency (AATD) iPSC line, PiZZ1. On day 15 of differentiation, we transfected cells with base editors to correct the AATD Z mutation. On day 21 of differentiation, we captured cells for 10x Genomics Single cell capture (V3 protocol). Control cells (MZ and MM stably corrected iHeps) were included in 1 lane, mixed at a ratio of 1:1 and then genotype was identified using the Vartrix Single-Cell Genotyping tool (10X Genomics). Louvain clustering identified 4 major clusters of cells, including a cluster of cells undergoing ER stress. Base editing decreased the number of cells undergoing ER stress. Overall design: Single-cell transcriptomic analysis of day 21 iPSC-derived hepatocytes comparing ZZ parental cells with base-edited cells and control (MZ and MM)