Pancreatic Inflammation Redirects Acinar to β Cell Reprogramming.

Clayton HW, Osipovich AB, Stancill JS, Schneider JD, Vianna PG, Shanks CM, Yuan W, Gu G, Manduchi E, Stoeckert CJ, Magnuson MA
Cell Rep. 2016 17 (8): 2028-2041

PMID: 27851966 · PMCID: PMC5131369 · DOI:10.1016/j.celrep.2016.10.068

Using a transgenic mouse model to express MafA, Pdx1, and Neurog3 (3TF) in a pancreatic acinar cell- and doxycycline-dependent manner, we discovered that the outcome of transcription factor-mediated acinar to β-like cellular reprogramming is dependent on both the magnitude of 3TF expression and on reprogramming-induced inflammation. Overly robust 3TF expression causes acinar cell necrosis, resulting in marked inflammation and acinar-to-ductal metaplasia. Generation of new β-like cells requires limiting reprogramming-induced inflammation, either by reducing 3TF expression or by eliminating macrophages. The new β-like cells were able to reverse streptozotocin-induced diabetes 6 days after inducing 3TF expression but failed to sustain their function after removal of the reprogramming factors.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

MeSH Terms (21)

Acinar Cells Adenoviridae Alleles Animals Cellular Reprogramming Diabetes Mellitus, Experimental Doxycycline Gene Expression Profiling Homeodomain Proteins Immunity Inflammation Insulin-Secreting Cells Macrophages Metaplasia Mice, Transgenic Organ Size Pancreas Pancreatic Ducts Reproducibility of Results Transcription Factors Transgenes

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