biostudies-literature00530Egozi AFannie Sherr FundEdmond de Rothschild FoundationsEuropean Research CouncilHoward Hughes Medical InstituteWolfson Family Charitable TrustIsrael Science FoundationBroad Institute-Israel Science FoundationBert L. and N. Kuggie Vallee FoundationChan Zuckerberg InitiativeHelen and Martin Kimmel Institute for Stem Cell ResearchEuropean Union’s Horizon 2020 research and innovation program108043https://www.ebi.ac.uk/biostudies/studies/S-EPMC7443616biostudies-literatureUnknown32(7)The islets of Langerhans are dynamic structures that can change in size, number of cells, and molecular function in response to physiological and pathological stress. Molecular cues originating from the surrounding "peri-islet" acinar cells that could facilitate this plasticity have not been explored. Here, we combine single-molecule transcript imaging in the intact pancreas and transcriptomics to identify spatial heterogeneity of acinar cell gene expression. We find that peri-islet acinar cells exhibit a distinct molecular signature in db/db diabetic mice that includes upregulation of trypsin family genes and elevated mTOR activity. This zonated expression program seems to be induced by CCK that is secreted from islet cells. Elevated peri-islet trypsin secretion could facilitate the islet expansion observed in this model via modulation of the islet capsule matrix components. Our study highlights a molecular axis of communication between the pancreatic exocrine and endocrine compartments that may be relevant to islet expansion.Cell reportsZonation of Pancreatic Acinar Cells in Diabetic Mice.PMC7443616CZF2019-0024342615/181486/16768956Farack LBahar Halpern KItzkovitz SEgozi ARotem H53falseZonation of Pancreatic Acinar Cells in Diabetic Mice.The islets of Langerhans are dynamic structures that can change in size, number of cells, and molecular function in response to physiological and pathological stress. Molecular cues originating from the surrounding "peri-islet" acinar cells that could facilitate this plasticity have not been explored. Here, we combine single-molecule transcript imaging in the intact pancreas and transcriptomics to identify spatial heterogeneity of acinar cell gene expression. We find that peri-islet acinar cells exhibit a distinct molecular signature in db/db diabetic mice that includes upregulation of trypsin family genes and elevated mTOR activity. This zonated expression program seems to be induced by CCK that is secreted from islet cells. Elevated peri-islet trypsin secretion could facilitate the islet expansion observed in this model via modulation of the islet capsule matrix components. Our study highlights a molecular axis of communication between the pancreatic exocrine and endocrine compartments that may be relevant to islet expansion.2020-01-01T00:00:00Z2020 Aug2024-11-10T03:03:20.689Z2020-08-31T07:29:58ZS-EPMC74436163281404610.1016/j.celrep.2020.108043