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Dev Cell. 2016 Nov 7;39(3):289-301. doi: 10.1016/j.devcel.2016.10.002. Epub 2016 Oct 27.

Single-Cell Analysis Uncovers Clonal Acinar Cell Heterogeneity in the Adult Pancreas.

Author information

1
Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
2
Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Institute of Applied Mathematics, University of Heidelberg, 69120 Heidelberg, Germany.
3
Department of Neurobiology and Behavior, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
4
Institute of Pathology, Technical University of Munich, 81675 Munich, Germany.
5
Institute of Applied Mathematics, University of Heidelberg, 69120 Heidelberg, Germany.
6
Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: a.martin-villalba@dkfz.de.

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.

KEYWORDS:

acinar cells; multicolor lineage tracing; organoids; pancreas; progenitors; single-cell sequencing

PMID:
27923766
DOI:
10.1016/j.devcel.2016.10.002
[Indexed for MEDLINE]
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