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

Canonical NOTCH signaling controls the early progenitor state and emergence of the medullary epithelial lineage in fetal thymus development

Dong Liu, Anastasia I. Kousa, Kathy E. O’Neill, Francois Guillemot, Martyna Popis, Alison M. Farley, Simon R. Tomlinson, View ORCID ProfileSvetlana Ulyanchenko, View ORCID ProfilePhilip A. Seymour, View ORCID ProfilePalle Serup, Ute Koch, Freddy Radtke, View ORCID ProfileC. Clare Blackburn
doi: https://doi.org/10.1101/600833
Dong Liu
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anastasia I. Kousa
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathy E. O’Neill
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Francois Guillemot
NNF Center for Stem Cell Biology, University of Copenhagen, Nørre Alle 14, DK-2200 Copenhagen N, DK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martyna Popis
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alison M. Farley
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon R. Tomlinson
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Svetlana Ulyanchenko
Biotech Research and Innovation Centre (BRIC), Ole Maaløes Vej 5, 2200 Copenhagen, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Svetlana Ulyanchenko
Philip A. Seymour
NNF Center for Stem Cell Biology, University of Copenhagen, Nørre Alle 14, DK-2200 Copenhagen N, DK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Philip A. Seymour
Palle Serup
NNF Center for Stem Cell Biology, University of Copenhagen, Nørre Alle 14, DK-2200 Copenhagen N, DK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Palle Serup
Ute Koch
Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne CH
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Freddy Radtke
Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne CH
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Clare Blackburn
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for C. Clare Blackburn
  • For correspondence: c.blackburn@ed.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Thymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. During thymus organogenesis, these functionally distinct sub-lineages are thought to arise from a common thymic epithelial progenitor cell (TEPC). The mechanisms controlling cTEC and mTEC production from the common TEPC are not however understood. Here, we show that emergence of the earliest mTEC lineage-restricted progenitors requires active NOTCH signaling in progenitor TEC and that, once specified, further mTEC development is NOTCH-independent. In addition, we demonstrate that persistent NOTCH activity favors maintenance of undifferentiated TEPC at the expense of cTEC differentiation. Finally, we uncover a direct interaction between NOTCH and FOXN1, the master regulator of TEC differentiation. These data establish NOTCH as a potent regulator of TEPC and mTEC fate during fetal thymus development and are thus of high relevance to strategies aimed at generating/regenerating functional thymic tissue in vitro and in vivo.

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 05, 2019.
Download PDF
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.
Canonical NOTCH signaling controls the early progenitor state and emergence of the medullary epithelial lineage in fetal thymus development
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Canonical NOTCH signaling controls the early progenitor state and emergence of the medullary epithelial lineage in fetal thymus development
Dong Liu, Anastasia I. Kousa, Kathy E. O’Neill, Francois Guillemot, Martyna Popis, Alison M. Farley, Simon R. Tomlinson, Svetlana Ulyanchenko, Philip A. Seymour, Palle Serup, Ute Koch, Freddy Radtke, C. Clare Blackburn
bioRxiv 600833; doi: https://doi.org/10.1101/600833
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Canonical NOTCH signaling controls the early progenitor state and emergence of the medullary epithelial lineage in fetal thymus development
Dong Liu, Anastasia I. Kousa, Kathy E. O’Neill, Francois Guillemot, Martyna Popis, Alison M. Farley, Simon R. Tomlinson, Svetlana Ulyanchenko, Philip A. Seymour, Palle Serup, Ute Koch, Freddy Radtke, C. Clare Blackburn
bioRxiv 600833; doi: https://doi.org/10.1101/600833

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

  • Developmental Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (1524)
  • Biochemistry (2479)
  • Bioengineering (1731)
  • Bioinformatics (9663)
  • Biophysics (3895)
  • Cancer Biology (2968)
  • Cell Biology (4188)
  • Clinical Trials (135)
  • Developmental Biology (2624)
  • Ecology (4097)
  • Epidemiology (2031)
  • Evolutionary Biology (6892)
  • Genetics (5204)
  • Genomics (6495)
  • Immunology (2182)
  • Microbiology (6936)
  • Molecular Biology (2751)
  • Neuroscience (17259)
  • Paleontology (126)
  • Pathology (425)
  • Pharmacology and Toxicology (705)
  • Physiology (1056)
  • Plant Biology (2487)
  • Scientific Communication and Education (643)
  • Synthetic Biology (831)
  • Systems Biology (2687)
  • Zoology (429)