Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Impact of sustained transforming growth factor-β receptor inhibition on chromatin accessibility and gene expression in cultured human endometrial MSC

Tools
- Tools
+ Tools

Lucciola, Raffaella, Vrljicak, Pavle, Gurung, Shanti, Filby, Caitlin, Darzi, Saeedeh, Muter, Joanne, Ott, Sascha, Brosens, Jan J. and Gargett, Caroline E. (2020) Impact of sustained transforming growth factor-β receptor inhibition on chromatin accessibility and gene expression in cultured human endometrial MSC. Frontiers in Cell and Developmental Biology, 8 . 567610. doi:10.3389/fcell.2020.567610 ISSN 2296-634X.

[img]
Preview
PDF
WRAP-Impact-sustained-growth-factor-β-receptor-chromatin-endometrial-Brosens-2020.pdf - Published Version - Requires a PDF viewer.
Available under License Creative Commons Attribution 4.0.

Download (4Mb) | Preview
Official URL: https://doi.org/10.3389/fcell.2020.567610

Request Changes to record.

Abstract

Endometrial mesenchymal stem cells (eMSC) drive the extraordinary regenerative capacity of the human endometrium. Clinical application of eMSC for therapeutic purposes is hampered by spontaneous differentiation and cellular senescence upon large-scale expansion in vitro. A83-01, a selective transforming growth factor-β receptor (TGFβ-R) inhibitor, promotes expansion of eMSC in culture by blocking differentiation and senescence, but the underlying mechanisms are incompletely understood. In this study, we combined RNA-seq and ATAC-seq to study the impact of sustained TGFβ-R inhibition on gene expression and chromatin architecture of eMSC. Treatment of primary eMSC with A83-01 for 5 weeks resulted in differential expression of 1,463 genes. Gene ontology analysis showed enrichment of genes implicated in cell growth whereas extracellular matrix genes and genes involved in cell fate commitment were downregulated. ATAC-seq analysis demonstrated that sustained TGFβ-R inhibition results in opening and closure of 3,555 and 2,412 chromatin loci, respectively. Motif analysis revealed marked enrichment of retinoic acid receptor (RAR) binding sites, which was paralleled by the induction of RARB, encoding retinoic acid receptor beta (RARβ). Selective RARβ inhibition attenuated proliferation and clonogenicity of A83-01 treated eMSC. Taken together, our study provides new insights into the gene networks and genome-wide chromatin changes that underpin maintenance of an undifferentiated phenotype of eMSC in prolonged culture.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Mesenchymal stem cells, Transforming growth factors-beta
Journal or Publication Title: Frontiers in Cell and Developmental Biology
Publisher: Frontiers Media
ISSN: 2296-634X
Official Date: 1 September 2020
Dates:
DateEvent
1 September 2020Published
13 August 2020Accepted
Volume: 8
Article Number: 567610
DOI: 10.3389/fcell.2020.567610
Status: Peer Reviewed
Publication Status: Published
Reuse Statement (publisher, data, author rights): Copyright © 2020 Lucciola, Vrljicak, Gurung, Filby, Darzi, Muter, Ott, Brosens and Gargett. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 3 September 2020
Date of first compliant Open Access: 7 September 2020
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
1081944National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
1159677National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
1042298National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
1173882National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
Operational Infrastructure Support ProgramState Government of Victoriahttp://dx.doi.org/10.13039/501100004752
Warwick-Monash Joint Ph.D. ScholarshipUniversity of Warwickhttp://dx.doi.org/10.13039/501100000741
212233/Z/18/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us