Single cell transcriptomic profiling of day 114 patient-specific pluripotent stem cell-derived alveolar epithelial type 2 cells expressing the SFTPCI73T mutation and their gene-edited corrected counterparts [D114]

We performed transcriptomic profiling of cells derived from human induced pluripotent stem cells (iPSCs) using our previously described distal lung directed differentiation protocol to generate alveolar epithelial type 2 cells (iAEC2s). We used the SPC2 human iPSC line and specifically the SPC2-ST-B2 (SFTPCtdT/WT) and SPC2-ST-C11 (SFTPCI73T/tdT) clones containing a SFTPCtdTomato knock-in reporter. SFTPCtdTomato+ cells were sorted on day 51 of differentiation and maintained without further sorting in self-renewing 3D alveolosphere cultures passaged approximately every 2 weeks through day 114. On day 114, all live cells were sorted and encapsulated for scRNA-seq using the 10X Chromium System. We find that mutant (SFTPCI73T/tdT) iAEC2s display a less proliferative and more mature AEC2 phenotype compared to their corrected (SFTPCtdT/WT) counterparts with a concomitant upregulation of lysosomal and autophagy related pathways in mutant cells. Overall design: Global transcriptomic profiling of day 114 patient-specific induced pluripotent stem cell (iPSC)-derived alveolar epithelial type 2 cells (iAEC2s) expressing the SFTPCI73T mutation and their gene-edited corrected counterparts by scRNA-seq