Single cell transcriptomes of pancreatic pre-invasive lesions and cancer reveal acinar metaplastic cells’ heterogeneity

In this project we have used single cell RNA-seq to profile pancreatic cancer development in a mouse model, from pre-invasive stage to cancer, and in human PDAC sample. Using a reporter gene, we were able to dissect metaplastic acinar cell heterogeneity, profiled six different acinar metaplastic cell types and states, validated their localization to pre-invasive lesions and correlated findings with human PDAC. In addition, we detected transcription factors, Onecut2 and Foxq1, that strictly expressed in metaplastic cells. Tamoxifen was injected into six-eight weeks old Ptf1a-CreER, LSL-Kras-G12D, LSL-tdTomato (PRT) mice, and the pancreas was collected for single cell purification from mice at six different time points post-tamoxifen injection (PTI)