TY - JOUR TI - Single-cell transcriptome analysis defines heterogeneity of the murine pancreatic ductal tree AU - Hendley, Audrey M AU - Rao, Arjun A AU - Leonhardt, Laura AU - Ashe, Sudipta AU - Smith, Jennifer A AU - Giacometti, Simone AU - Peng, Xianlu L AU - Jiang, Honglin AU - Berrios, David I AU - Pawlak, Mathias AU - Li, Lucia Y AU - Lee, Jonghyun AU - Collisson, Eric A AU - Anderson, Mark S AU - Fragiadakis, Gabriela K AU - Yeh, Jen Jen AU - Ye, Chun Jimmie AU - Kim, Grace E AU - Weaver, Valerie M AU - Hebrok, Matthias A2 - Sussel, Lori A2 - Stainier, Didier YR VL - 10 PY - 2021 DA - 2021/05/19 SP - e67776 C1 - eLife 2021;10:e67776 DO - 10.7554/eLife.67776 UR - https://doi.org/10.7554/eLife.67776 AB - 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. KW - scRNA-seq KW - pancreatic duct ligation KW - Osteopontin KW - Geminin KW - duct heterogeneity JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -