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The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis. Nat Commun 2023 Jan 03;14(1):1

Date

01/04/2023

Pubmed ID

36596776

Pubmed Central ID

PMC9810714

DOI

10.1038/s41467-022-34464-6

Scopus ID

2-s2.0-85145429848 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

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 profiling identifies gene expression signatures that are shared among the fetal splanchnic mesenchyme, adult fibroblasts and CAFs, suggesting a persistent transcriptional program underlies splanchnic lineage differentiation. Together, this study defines the phylogeny of the mesenchymal component of the pancreas and provides insights into pancreatic morphogenesis and tumorigenesis.

Author List

Han L, Wu Y, Fang K, Sweeney S, Roesner UK, Parrish M, Patel K, Walter T, Piermattei J, Trimboli A, Lefler J, Timmers CD, Yu XZ, Jin VX, Zimmermann MT, Mathison AJ, Urrutia R, Ostrowski MC, Leone G

Authors

Victor X. Jin PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of Wisconsin
Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin
Yongxia Wu PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Xue-Zhong Yu MD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Michael T. Zimmermann PhD Director, Assistant Professor in the Clinical and Translational Science Institute department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Carcinogenesis
Cell Transformation, Neoplastic
Fibroblasts
Homeostasis
Mesoderm
Mice
Pancreas
Pancreatic Neoplasms