A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis

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 sin...

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Autores: Fernández, Ángel, Casamitjana, Joan, Holguín-Horcajo, Adrián, Coolens, Katarina, Mularoni, Loris, Guo, Li, Hartwig, Olga, Düking, Tim, Vidal, Noemi, Strickland, Lincoln N., Pasquali, Lorenzo, Bailey-Lundberg, Jennifer M., Rooman, Ilse, Wang, Yue J., Rovira, Meritxell
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/215968
Acesso em linha:https://hdl.handle.net/2445/215968
Access Level:acceso abierto
Palavra-chave:Regeneració (Biologia)
Pàncrees
Teixits (Histologia)
Regeneration (Biology)
Pancreas
Tissues
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spelling A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesisFernández, ÁngelCasamitjana, JoanHolguín-Horcajo, AdriánCoolens, KatarinaMularoni, LorisGuo, LiHartwig, OlgaDüking, TimVidal, NoemiStrickland, Lincoln N.Pasquali, LorenzoBailey-Lundberg, Jennifer M.Rooman, IlseWang, Yue J.Rovira, MeritxellRegeneració (Biologia)PàncreesTeixits (Histologia)Regeneration (Biology)PancreasTissuesBackground & 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.Elsevier2024202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion32 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/215968Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1053/j.gastro.2024.06.008Gastroenterology, 2024, vol. 167, num.5, p. 944-960https://doi.org/10.1053/j.gastro.2024.06.008cc-by-nc-nd (c) Fernández, Ángel et al., 2024http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2159682026-05-29T05:05:01Z
dc.title.none.fl_str_mv A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
title A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
spellingShingle A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
Fernández, Ángel
Regeneració (Biologia)
Pàncrees
Teixits (Histologia)
Regeneration (Biology)
Pancreas
Tissues
title_short A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
title_full A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
title_fullStr A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
title_full_unstemmed A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
title_sort A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
dc.creator.none.fl_str_mv Fernández, Ángel
Casamitjana, Joan
Holguín-Horcajo, Adrián
Coolens, Katarina
Mularoni, Loris
Guo, Li
Hartwig, Olga
Düking, Tim
Vidal, Noemi
Strickland, Lincoln N.
Pasquali, Lorenzo
Bailey-Lundberg, Jennifer M.
Rooman, Ilse
Wang, Yue J.
Rovira, Meritxell
author Fernández, Ángel
author_facet Fernández, Ángel
Casamitjana, Joan
Holguín-Horcajo, Adrián
Coolens, Katarina
Mularoni, Loris
Guo, Li
Hartwig, Olga
Düking, Tim
Vidal, Noemi
Strickland, Lincoln N.
Pasquali, Lorenzo
Bailey-Lundberg, Jennifer M.
Rooman, Ilse
Wang, Yue J.
Rovira, Meritxell
author_role author
author2 Casamitjana, Joan
Holguín-Horcajo, Adrián
Coolens, Katarina
Mularoni, Loris
Guo, Li
Hartwig, Olga
Düking, Tim
Vidal, Noemi
Strickland, Lincoln N.
Pasquali, Lorenzo
Bailey-Lundberg, Jennifer M.
Rooman, Ilse
Wang, Yue J.
Rovira, Meritxell
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Regeneració (Biologia)
Pàncrees
Teixits (Histologia)
Regeneration (Biology)
Pancreas
Tissues
topic Regeneració (Biologia)
Pàncrees
Teixits (Histologia)
Regeneration (Biology)
Pancreas
Tissues
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/215968
url https://hdl.handle.net/2445/215968
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1053/j.gastro.2024.06.008
Gastroenterology, 2024, vol. 167, num.5, p. 944-960
https://doi.org/10.1053/j.gastro.2024.06.008
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Fernández, Ángel et al., 2024
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Fernández, Ángel et al., 2024
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 32 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419858173624320
score 15,811543

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