Transcriptomic profiling of day 194 patient-specific pluripotent stem cell-derived alveolar epithelial type 2 cells expressing the SFTPCC121Y mutation and their gene-edited corrected counterparts
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 (iAT2s). We used the SPC8 human iPSC line and specifically the SPC8-ST-Corr (SFTPCtdT/WT) and SPC8-ST-Mut (SFTPCC121Y/tdT) clones containing a SFTPCtdTomato knock-in reporter. SFTPCtdTomato+ cells were sorted on days 45, 87 and 182 of differentiation. iAT2s were single-cell passaged in self-renewing 3D alveolosphere cultures approximately every 10-14 days through day 194. On day 194, all live cells were sorted and encapsulated for scRNA-seq using the 10X Chromium System. We find that a subset of mutant (SFTPCC121Y/tdT) iAT2s develops an aberrant transitional cell state. Overall design: Global transcriptomic profiling of day 194 patient-specific induced pluripotent stem cell (iPSC)-derived alveolar epithelial type 2 cells (iAT2s) expressing the SFTPCC121Y mutation and their gene-edited corrected counterparts by scRNA-seq