Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas

View ORCID ProfileDavid J. Falvo, Adrien Grimont, Paul Zumbo, View ORCID ProfileJulie L. Yang, Alexa Osterhoudt, Grace Pan, View ORCID ProfileAndre F. Rendeiro, John E. Wilkinson, Friederike Dündar, Olivier Elemento, Rhonda K. Yantiss, Doron Betel, Richard Koche, View ORCID ProfileRohit Chandwani
doi: https://doi.org/10.1101/2021.11.01.466807
David J. Falvo
1Department of Surgery, Weill Cornell Medicine, New York, NY, 10065, USA
2Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David J. Falvo
Adrien Grimont
1Department of Surgery, Weill Cornell Medicine, New York, NY, 10065, USA
2Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul Zumbo
3Institute for Computational Biomedicine, Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, 10065, USA
4Applied Bioinformatics Core, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julie L. Yang
5Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Julie L. Yang
Alexa Osterhoudt
1Department of Surgery, Weill Cornell Medicine, New York, NY, 10065, USA
2Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Grace Pan
1Department of Surgery, Weill Cornell Medicine, New York, NY, 10065, USA
2Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andre F. Rendeiro
3Institute for Computational Biomedicine, Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, 10065, USA
6Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Andre F. Rendeiro
John E. Wilkinson
7Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Friederike Dündar
3Institute for Computational Biomedicine, Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, 10065, USA
4Applied Bioinformatics Core, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olivier Elemento
3Institute for Computational Biomedicine, Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, 10065, USA
6Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rhonda K. Yantiss
8Department of Pathology, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Doron Betel
3Institute for Computational Biomedicine, Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, 10065, USA
4Applied Bioinformatics Core, Weill Cornell Medicine, New York, NY, 10065, USA
9Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Koche
5Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rohit Chandwani
1Department of Surgery, Weill Cornell Medicine, New York, NY, 10065, USA
2Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10065, USA
10Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rohit Chandwani
  • For correspondence: roc9045@med.cornell.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

SUMMARY

Inflammation is essential to the disruption of tissue homeostasis, and, in the pancreas, can destabilize the identity of terminally differentiated acinar cells. Herein we employ lineage-traced mouse models to delineate the chromatin dynamics that accompany the cycle of metaplasia and regeneration following pancreatitis, and unveil the presence of an epigenetic memory of inflammation in the pancreatic acinar cell compartment. We observe that despite histologic resolution of pancreatitis, acinar cells fail to return to their molecular baseline after several months, representing an incomplete cell fate decision. In vivo, this epigenetic memory controls lineage plasticity, with diminished metaplasia in response to a second inflammatory insult but increased tumorigenesis with an oncogenic Kras mutation. We demonstrate that both persistent chromatin and transcriptional changes constituting memory are recalled with oncogenic stress. Together, our findings define the dynamics and recall of an epigenetic memory of inflammation that impacts cell fate decisions in a context-dependent manner.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted April 06, 2022.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas
David J. Falvo, Adrien Grimont, Paul Zumbo, Julie L. Yang, Alexa Osterhoudt, Grace Pan, Andre F. Rendeiro, John E. Wilkinson, Friederike Dündar, Olivier Elemento, Rhonda K. Yantiss, Doron Betel, Richard Koche, Rohit Chandwani
bioRxiv 2021.11.01.466807; doi: https://doi.org/10.1101/2021.11.01.466807
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas
David J. Falvo, Adrien Grimont, Paul Zumbo, Julie L. Yang, Alexa Osterhoudt, Grace Pan, Andre F. Rendeiro, John E. Wilkinson, Friederike Dündar, Olivier Elemento, Rhonda K. Yantiss, Doron Betel, Richard Koche, Rohit Chandwani
bioRxiv 2021.11.01.466807; doi: https://doi.org/10.1101/2021.11.01.466807

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cancer Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3580)
  • Biochemistry (7534)
  • Bioengineering (5488)
  • Bioinformatics (20709)
  • Biophysics (10267)
  • Cancer Biology (7942)
  • Cell Biology (11597)
  • Clinical Trials (138)
  • Developmental Biology (6576)
  • Ecology (10151)
  • Epidemiology (2065)
  • Evolutionary Biology (13565)
  • Genetics (9504)
  • Genomics (12801)
  • Immunology (7891)
  • Microbiology (19472)
  • Molecular Biology (7624)
  • Neuroscience (41939)
  • Paleontology (307)
  • Pathology (1253)
  • Pharmacology and Toxicology (2182)
  • Physiology (3254)
  • Plant Biology (7017)
  • Scientific Communication and Education (1291)
  • Synthetic Biology (1944)
  • Systems Biology (5412)
  • Zoology (1109)