title: Single-Cell Analysis Uncovers Clonal Acinar Cell Heterogeneity in the Adult Pancreas.
abstract: Acinar cells make up the majority of all cells in the pancreas, yet the source of new acinar cells during homeostasis remains unknown. Using multicolor lineage-tracing and organoid-formation assays, we identified the presence of a progenitor-like acinar cell subpopulation. These cells have long-term self-renewal capacity, albeit in a unipotent fashion. We further demonstrate that binuclear acinar cells are terminally differentiated acinar cells. Transcriptome analysis of single acinar cells revealed the existence of a minor population of cells expressing progenitor markers. Interestingly, a gain of the identified markers accompanied by a transient gain of proliferation was observed following chemically induced pancreatitis. Altogether, our study identifies a functionally and molecularly distinct acinar subpopulation and thus transforms our understanding of the acinar cell compartment as a pool of equipotent secretory cells.
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Damian
authors.initials: D
authors.lastname: Wollny
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Everlien
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Lun
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Brunken
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brüne
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Institute of Applied Mathematics, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Ziebell
authors.affiliation: Department of Neurobiology and Behavior, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Tabansky
authors.affiliation: Institute of Pathology, Technical University of Munich, 81675 Munich, Germany.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.affiliation: Institute of Applied Mathematics, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Marciniak-Czochra
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: a.martin-villalba@dkfz.de.
authors.forename: Ana
authors.initials: A
authors.lastname: Martin-Villalba
mesh_terms: D061354:Acinar Cells / Q000166:cytology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002999:Clone Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D009940:Organoids / Q000166:cytology; D010179:Pancreas / Q000166:cytology*; D059010:Single-Cell Analysis / Q000379:methods*; D050777:Stathmin / Q000378:metabolism
chemical_list: D050777:Stathmin; C493994:Stmn1 protein, mouse
keywords: acinar cells; multicolor lineage tracing; organoids; pancreas; progenitors; single-cell sequencing