Organoid modeling reveals the tumorigenic potential of the alveolar progenitor cell state

The goal of this study was to investigate the transcriptional and epigenetic changes after the onset of KrasG12D and P53 Loss in Alveolar type 2 (AT2) cells using organoid model. Single cell Multi-omic sequencing were performed on 7 days tumor organoids which were derived from induced AT2 cells. Overall design: AT2 cells were isolated from KrasLSL-G12D/WT; P53flox/flox; Rosa26LSL-eYFP (KPY) mice using well established surface marker (CD31-/CD45-/Epcam+/Sca1-). The freshly sorted AT2 cells were induced with Adenovirus containing Cre recombinase. Then, the induced AT2 cells were co-cultured with lung stromal cells at air-liquid interface for deriving tumor organoids. After 7 days culture, the organoids were digested into single cells and FACS sorted YFP+ epithelial cells. scMulti-omic sequencing was performed using the 10X genomics platform (Chromium Next GEM Single Cell Multiome ATAC + Gene Expression kit, PN-1000285)