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

Clonal Architecture of the Epidermis: Homeostasis Limits Keratinocyte Evolution

View ORCID ProfileRyan O. Schenck, Eunjung Kim, View ORCID ProfileRafael R. Bravo, View ORCID ProfileJeffrey West, View ORCID ProfileSimon Leedham, View ORCID ProfileDarryl Shibata, View ORCID ProfileAlexander R.A. Anderson
doi: https://doi.org/10.1101/548131
Ryan O. Schenck
1Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
2Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX37BN, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ryan O. Schenck
Eunjung Kim
1Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rafael R. Bravo
1Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rafael R. Bravo
Jeffrey West
1Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jeffrey West
Simon Leedham
2Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX37BN, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Simon Leedham
Darryl Shibata
3Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Darryl Shibata
Alexander R.A. Anderson
1Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alexander R.A. Anderson
  • For correspondence: Alexander.Anderson@moffitt.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The skin is the largest human organ, functioning to serve as the protective barrier to the harsh, outside world. Recent studies have revealed that large numbers of somatic mutations accumulate in normal tissue, which can be used to infer skin cell dynamics1-5. Here we present the first realistic, cell-genome mechanistic epidermal model that shows homeostasis imposes a characteristic log-linear subclone size distribution for both neutral and oncogenic driver mutations, where the largest skin subclones are the oldest subclones. Because homeostasis inherently limits proliferation and therefore clonal sweeps, selection for driver mutations (NOTCH1 and TP53) in normal epidermis is instead conferred by greater persistence, which leads to larger subclone sizes. These results highlight how the integration of mechanistic modeling with genomic data provide novel insights into the evolutionary cell dynamics of normal human homeostatic tissues.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted February 14, 2019.
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.
Clonal Architecture of the Epidermis: Homeostasis Limits Keratinocyte Evolution
(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
Clonal Architecture of the Epidermis: Homeostasis Limits Keratinocyte Evolution
Ryan O. Schenck, Eunjung Kim, Rafael R. Bravo, Jeffrey West, Simon Leedham, Darryl Shibata, Alexander R.A. Anderson
bioRxiv 548131; doi: https://doi.org/10.1101/548131
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Clonal Architecture of the Epidermis: Homeostasis Limits Keratinocyte Evolution
Ryan O. Schenck, Eunjung Kim, Rafael R. Bravo, Jeffrey West, Simon Leedham, Darryl Shibata, Alexander R.A. Anderson
bioRxiv 548131; doi: https://doi.org/10.1101/548131

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

  • Evolutionary Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4113)
  • Biochemistry (8815)
  • Bioengineering (6519)
  • Bioinformatics (23462)
  • Biophysics (11789)
  • Cancer Biology (9209)
  • Cell Biology (13322)
  • Clinical Trials (138)
  • Developmental Biology (7436)
  • Ecology (11409)
  • Epidemiology (2066)
  • Evolutionary Biology (15150)
  • Genetics (10436)
  • Genomics (14043)
  • Immunology (9171)
  • Microbiology (22154)
  • Molecular Biology (8812)
  • Neuroscience (47569)
  • Paleontology (350)
  • Pathology (1428)
  • Pharmacology and Toxicology (2491)
  • Physiology (3730)
  • Plant Biology (8080)
  • Scientific Communication and Education (1437)
  • Synthetic Biology (2221)
  • Systems Biology (6037)
  • Zoology (1253)