Single cell transcriptome analysis defines heterogeneity of the murine pancreatic ductal tree
- University of California, San Francisco, United States
- BlueRock Therapeutics, United States
- University of North Carolina Chapel Hill, United States
Abstract
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.
Data availability
Sequencing data have been deposited in GEO under accession code GSE159343.
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Single cell RNA-seq defines novel heterogeneity within the pancreatic ductal treeNCBI Gene Expression Omnibus,GSE159343.
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Lineage dynamics of pancreatic development at single cell resolutionNCBI Gene Expression Omnibus, GSE101099.
Article and author information
Author details
Funding
National Cancer Institute (F32 CA221114)
- Audrey Marie Hendley
Hirshberg Foundation for Pancreatic Cancer Research (Seed Grant)
- Audrey Marie Hendley
National Cancer Institute (R01 CA222862)
- Eric A Collisson
National Cancer Institute (R01 CA172045)
- Matthias Hebrok
Parker Institute for Cancer Immunotherapy (PICI Opportunity Grant)
- Matthias Hebrok
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (AN170192) of the University of California San Francisco.
Copyright
© 2021, Hendley et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Single cell transcriptome analysis defines heterogeneity of the murine pancreatic ductal tree
eLife 10:e67776.
https://doi.org/10.7554/eLife.67776
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