RT Journal Article
SR Electronic
T1 Single cell transcriptome analysis defines heterogeneity of the adult murine pancreatic ductal tree
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.12.336784
DO 10.1101/2020.10.12.336784
A1 Audrey M. Hendley
A1 Arjun A. Rao
A1 Laura Leonhardt
A1 Sudipta Ashe
A1 Jennifer A. Smith
A1 Simone Giacometti
A1 Xianlu L Peng
A1 Honglin Jiang
A1 David I. Berrios
A1 Mathias Pawlak
A1 Lucia Y. Li
A1 Jonghyun Lee
A1 Eric A. Collisson
A1 Mark Anderson
A1 Gabriela K. Fragiadakis
A1 Jen Jen Yeh
A1 Jimmie Ye Chun
A1 Grace E. Kim
A1 Valerie M. Weaver
A1 Matthias Hebrok
YR 2020
UL http://biorxiv.org/content/early/2020/10/28/2020.10.12.336784.abstract
AB Lineage tracing using genetically engineered mouse models is an essential tool for investigating cell-fate decisions of progenitor cells and biology of mature cell types, with relevance to physiology and disease progression. To study disease development, an inventory of an organ’s cell types and understanding of physiologic function is paramount. Here, we performed singlecell RNA sequencing to examine heterogeneity of murine pancreatic duct cells, pancreatobiliary cells, and intrapancreatic bile duct cells. We isolated duct cells within the murine pancreas using a Dolichos biflorus agglutinin (DBA) lectin sorting strategy that labels all pancreatic duct cell types. Our data suggested the substructure of murine pancreatic duct cells is compartmentalized into three subpopulations. We describe an epithelial-mesenchymal transitory axis in our three pancreatic duct subpopulations and identify SPP1 as a regulator of this fate decision as well as human duct cell de-differentiation. 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.SIGNIFICANCE Murine models are extensively used for pancreatic lineage tracing experiments and investigation of pancreatic disease progression. Here, we describe the transcriptome of murine pancreatic duct cells, intrapancreatic bile duct cells, and pancreatobiliary cells at single cell resolution. Our analysis defines novel heterogeneity within the pancreatic ductal tree and supports the paradigm that more than one population of pancreatic duct cells harbors progenitor capacity. We identify and validate unique functional properties of subpopulations of pancreatic duct cells including an epithelial-mesenchymal transcriptomic axis and roles in chronic pancreatic inflammation.Competing Interest StatementThe authors have declared no competing interest.