Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2016 Nov 15;17(8):2028-2041. doi: 10.1016/j.celrep.2016.10.068.

Pancreatic Inflammation Redirects Acinar to β Cell Reprogramming.

Author information

  • 1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA; Center for Stem Cell Biology, Vanderbilt University, Nashville, TN 37232, USA.
  • 2Center for Stem Cell Biology, Vanderbilt University, Nashville, TN 37232, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
  • 3Center for Stem Cell Biology, Vanderbilt University, Nashville, TN 37232, USA.
  • 4Institute for Biomedical Informatics and Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • 5Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA; Center for Stem Cell Biology, Vanderbilt University, Nashville, TN 37232, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: mark.magnuson@vanderbilt.edu.

Abstract

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.

KEYWORDS:

acinar cells; acinar-to-ductal metaplasia; beta cells; diabetes; inflammation; pancreas; reprogramming

PMID:
27851966
PMCID:
PMC5131369
DOI:
10.1016/j.celrep.2016.10.068
[PubMed - in process]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center