Diabetes Center, University of California, San Francisco, San Francisco, United States; Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, United States
Arjun A Rao
CoLabs, University of California, San Francisco, San Francisco, United States; Bakar ImmunoX Initiative, University of California, San Francisco, San Francisco, United States
Laura Leonhardt
Diabetes Center, University of California, San Francisco, San Francisco, United States
Sudipta Ashe
Diabetes Center, University of California, San Francisco, San Francisco, United States
Jennifer A Smith
Diabetes Center, University of California, San Francisco, San Francisco, United States
Simone Giacometti
Diabetes Center, University of California, San Francisco, San Francisco, United States
Xianlu L Peng
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, United States
Honglin Jiang
Division of Hematology and Oncology, Department of Medicine and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, United States
David I Berrios
Diabetes Center, University of California, San Francisco, San Francisco, United States
Mathias Pawlak
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, United States
Lucia Y Li
Diabetes Center, University of California, San Francisco, San Francisco, United States
Jonghyun Lee
Diabetes Center, University of California, San Francisco, San Francisco, United States
Division of Hematology and Oncology, Department of Medicine and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, United States
Diabetes Center, University of California, San Francisco, San Francisco, United States
Gabriela K Fragiadakis
CoLabs, University of California, San Francisco, San Francisco, United States; Bakar ImmunoX Initiative, University of California, San Francisco, San Francisco, United States; Department of Medicine, Division of Rheumatology, University of California, San Francisco, San Francisco, United States
Jen Jen Yeh
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, United States; Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, United States
Chun Jimmie Ye
Parker Institute for Cancer Immunotherapy, San Francisco, United States
Grace E Kim
Department of Pathology, University of California, San Francisco, San Francisco, United States
Valerie M Weaver
Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, United States
To study disease development, an inventory of an organ's cell types and understanding of physiologic function is paramount. Here, we performed single-cell RNA-sequencing to examine heterogeneity of murine pancreatic duct cells, pancreatobiliary cells, and intrapancreatic bile duct cells. We describe an epithelial-mesenchymal transitory axis in our three pancreatic duct subpopulations and identify osteopontin as a regulator of this fate decision as well as human duct cell dedifferentiation. Our results further identify functional heterogeneity within pancreatic duct subpopulations by elucidating a role for geminin in accumulation of DNA damage in the setting of chronic pancreatitis. Our findings implicate diverse functional roles for subpopulations of pancreatic duct cells in maintenance of duct cell identity and disease progression and establish a comprehensive road map of murine pancreatic duct cell, pancreatobiliary cell, and intrapancreatic bile duct cell homeostasis.
