The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis

Pancreatic cancer is characterized by abundant desmoplasia, a dense stroma composed of extra-cellular and cellular components, with cancer associated fibroblasts (CAFs) being the major cellular component. However, the tissue(s) of origin for CAFs remains controversial. Here we determine the tissue origin of pancreatic CAFs through comprehensive lineage tracing studies in mice. We find that the splanchnic mesenchyme, the fetal cell layer surrounding the endoderm from which the pancreatic epithelium originates, gives rise to the majority of resident fibroblasts in the normal pancreas. In a genetic mouse model of pancreatic cancer, resident fibroblasts expand and constitute the bulk of CAFs. Single cell RNA…

• NI
  National Institutes of Health

  Awards: NCI R01, AI118305, R01 DK052913, NIDDK R01, NIAID R01
• MC
  Medical College of Wisconsin Cancer Center
• NC
  National Cancer Institute

  Awards: CA258440, P01 CA236778, CA236778, R01 CA258440, T32CA193201
• NI
  National Institute of Allergy and Infectious Diseases

  Award: AI118305
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases

  Awards: R01 DK052913, DK052913