A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
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- dc.contributor.author Fernández, Ángel
- dc.contributor.author Casamitjana, Joan
- dc.contributor.author Holguín Horcajo, Adrián
- dc.contributor.author Coolens, Katarina
- dc.contributor.author Mularoni, Loris
- dc.contributor.author Guo, Li
- dc.contributor.author Hartwig, Olga
- dc.contributor.author Düking, Tim
- dc.contributor.author Vidal, Noemí
- dc.contributor.author Strickland, Lincoln N.
- dc.contributor.author Pasquali, Lorenzo
- dc.contributor.author Bailey-Lundberg, Jennifer M.
- dc.contributor.author Rooman, Ilse
- dc.contributor.author Wang, Yue J.
- dc.contributor.author Rovira, Meritxell
- dc.date.accessioned 2024-11-12T06:36:44Z
- dc.date.available 2024-11-12T06:36:44Z
- dc.date.issued 2024
- dc.description.abstract Background & aims: Pancreatic ducts form an intricate network of tubules that secrete bicarbonate and drive acinar secretions into the duodenum. This network is formed by centroacinar cells, terminal, intercalated, intracalated ducts, and the main pancreatic duct. Ductal heterogeneity at the single-cell level has been poorly characterized; therefore, our understanding of the role of ductal cells in pancreas regeneration and exocrine pathogenesis has been hampered by the limited knowledge and unexplained diversity within the ductal network. Methods: We used single cell RNA sequencing to comprehensively characterize mouse ductal heterogeneity at single-cell resolution of the entire ductal epithelium from centroacinar cells to the main duct. Moreover, we used organoid cultures, injury models, and pancreatic tumor samples to interrogate the role of novel ductal populations in pancreas regeneration and exocrine pathogenesis. Results: We have identified the coexistence of 15 ductal populations within the healthy pancreas and characterized their organoid formation capacity and endocrine differentiation potential. Cluster isolation and subsequent culturing let us identify ductal cell populations with high organoid formation capacity and endocrine and exocrine differentiation potential in vitro, including a Wnt-responsive population, a ciliated population, and Flrt3+ cells. Moreover, we have characterized the location of these novel ductal populations in healthy pancreas, chronic pancreatitis, and tumor samples. The expression of Wnt-responsive, interferon-responsive, and epithelial-to-mesenchymal transition population markers increases in chronic pancreatitis and tumor samples. Conclusions: In light of our discovery of previously unidentified ductal populations, we unmask potential roles of specific ductal populations in pancreas regeneration and exocrine pathogenesis. Thus, novel lineage-tracing models are needed to investigate ductal-specific populations in vivo.
- dc.format.mimetype application/pdf
- dc.identifier.citation Fernández Á, Casamitjana J, Holguín-Horcajo A, Coolens K, Mularoni L, Guo L, et al. A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis. Gastroenterology. 2024 Oct;167(5):944-60.e15. DOI: 10.1053/j.gastro.2024.06.008
- dc.identifier.doi http://dx.doi.org/10.1053/j.gastro.2024.06.008
- dc.identifier.issn 0016-5085
- dc.identifier.uri http://hdl.handle.net/10230/68495
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Gastroenterology. 2024 Oct;167(5):944-60.e15
- dc.rights © 2024 The Author(s). Published by Elsevier Inc. on behalf of the AGA Institute. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword Ductal cells
- dc.subject.keyword Exocrine pathologies
- dc.subject.keyword Organoids
- dc.subject.keyword Pancreas regeneration
- dc.subject.keyword scRNA-Seq
- dc.title A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion