A Transcriptionally Distinct Subpopulation of Healthy Acinar Cells Exhibit Features of Pancreatic Progenitors and PDAC.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) tumors can originate either from acinar or ductal cells in the adult pancreas. We re-analyze multiple pancreas and PDAC single-cell RNA-seq datasets and find a subset of nonmalignant acinar cells, which we refer to as acinar edge (AE) cells, whose transcriptomes highly diverge from a typical acinar cell in each dataset. Genes upregulated among AE cells are enriched for transcriptomic signatures of pancreatic progenitors, acinar dedifferentiation, and several oncogenic programs. AE-upregulated genes are upregulated in human PDAC tumors, and consistently, their promoters are hypomethylated. High expression of these genes is associated with poor patient survival. The fraction of AE-like cells increases with age in healthy pancreatic tissue, which is not

SUBMITTER: Gopalan V 

PROVIDER: S-EPMC8338776 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature