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Merck

Zonation of Pancreatic Acinar Cells in Diabetic Mice.

Cell reports (2020-08-20)
Adi Egozi, Keren Bahar Halpern, Lydia Farack, Hagar Rotem, Shalev Itzkovitz
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Insulin from bovine pancreas, γ-irradiated, BioXtra, suitable for cell culture, potency: ≥20 units/mg (USP units), lyophilized powder
Sigma-Aldrich
(Tyr[SO3H]27)Cholecystokinin fragment 26-33 Amide, ≥97% (HPLC), powder
Sigma-Aldrich
TRI Reagent®, For processing tissues, cells cultured in monolayer or cell pellets
Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
Ribonucleic acid, transfer from Escherichia coli, Type XX, Strain W, lyophilized powder
Sigma-Aldrich
Dextran sulfate sodium salt from Leuconostoc spp., for molecular biology, average Mw >500,000 (dextran starting material), contains 0.5-2% phosphate buffer
Sigma-Aldrich
Poly(ethylene glycol), BioUltra, 8,000