A Single-Cell Atlas of the Murine Pancreatic Ductal Tree Identifies Novel Cell Populations With Potential Implications in Pancreas Regeneration and Exocrine Pathogenesis.

Autor:	Fernández Á; Department of Physiological Science, School of Medicine, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain; Pancreas Regeneration: Pancreatic Progenitors and Their Niche Group, Regenerative Medicine Program, Instituto de Investigación Biomédica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain; Program for Advancing the Clinical Translation of Regenerative Medicine of Catalonia, P-CMR[C], L'Hospitalet de Llobregat, Spain; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain., Casamitjana J; Department of Physiological Science, School of Medicine, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain; Pancreas Regeneration: Pancreatic Progenitors and Their Niche Group, Regenerative Medicine Program, Instituto de Investigación Biomédica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain; Program for Advancing the Clinical Translation of Regenerative Medicine of Catalonia, P-CMR[C], L'Hospitalet de Llobregat, Spain., Holguín-Horcajo A; Department of Physiological Science, School of Medicine, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain; Pancreas Regeneration: Pancreatic Progenitors and Their Niche Group, Regenerative Medicine Program, Instituto de Investigación Biomédica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain; Program for Advancing the Clinical Translation of Regenerative Medicine of Catalonia, P-CMR[C], L'Hospitalet de Llobregat, Spain., Coolens K; Vrije Universiteit Brussel, Translational Oncology Research Center, Laboratory for Medical and Molecular Oncology, Brussels, Belgium., Mularoni L; Program for Advancing the Clinical Translation of Regenerative Medicine of Catalonia, P-CMR[C], L'Hospitalet de Llobregat, Spain., Guo L; Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida., Hartwig O; Miltenyi Biotec B.V. & Co KG, Bergisch Gladbach, Germany., Düking T; Miltenyi Biotec B.V. & Co KG, Bergisch Gladbach, Germany., Vidal N; Pathology Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain., Strickland LN; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas., Pasquali L; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain., Bailey-Lundberg JM; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas., Rooman I; Vrije Universiteit Brussel, Translational Oncology Research Center, Laboratory for Medical and Molecular Oncology, Brussels, Belgium., Wang YJ; Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida., Rovira M; Department of Physiological Science, School of Medicine, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain; Pancreas Regeneration: Pancreatic Progenitors and Their Niche Group, Regenerative Medicine Program, Instituto de Investigación Biomédica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain; Program for Advancing the Clinical Translation of Regenerative Medicine of Catalonia, P-CMR[C], L'Hospitalet de Llobregat, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Barcelona, Spain. Electronic address: mrovira@idibell.cat.
Jazyk:	angličtina
Zdroj:	Gastroenterology [Gastroenterology] 2024 Oct; Vol. 167 (5), pp. 944-960.e15. Date of Electronic Publication: 2024 Jun 21.
DOI:	10.1053/j.gastro.2024.06.008
Abstrakt:	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. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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