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

Transcriptional programs define intratumoral heterogeneity of Ewing sarcoma at single cell resolution

M-M Aynaud, View ORCID ProfileO Mirabeau, View ORCID ProfileN Gruel, S Grossetête, View ORCID ProfileV Boeva, S Durand, View ORCID ProfileD Surdez, View ORCID ProfileO Saulnier, S Zaïdi, View ORCID ProfileS Gribkova, View ORCID ProfileU Kairov, V Raynal, F Tirode, View ORCID ProfileTGP Grünewald, M Bohec, View ORCID ProfileS Baulande, View ORCID ProfileI Janoueix-Lerosey, View ORCID ProfileJ-P Vert, View ORCID ProfileE Barillot, View ORCID ProfileO Delattre, View ORCID ProfileA Zinovyev
doi: https://doi.org/10.1101/623710
M-M Aynaud
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
O Mirabeau
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for O Mirabeau
N Gruel
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
2Institut Curie, PSL Research University, Department of Translational Research, 75005, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for N Gruel
S Grossetête
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
V Boeva
3Institut Curie, PSL Research University, INSERM, U900, Mines-ParisTech, Paris, France
4Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes UMR-S1016, 75014, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for V Boeva
S Durand
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D Surdez
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for D Surdez
O Saulnier
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for O Saulnier
S Zaïdi
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S Gribkova
3Institut Curie, PSL Research University, INSERM, U900, Mines-ParisTech, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for S Gribkova
U Kairov
5Laboratory of Bioinformatics and Systems Biology, Center for Life Sciences, National Laboratory, Nazarbayev University, Astana, Kazakhstan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for U Kairov
V Raynal
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
F Tirode
6University of Lyon, Université Claude Bernard Lyon 1, CNRS 5286, INSERM U1052, Cancer Research Centre of Lyon, 69008, Lyon, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TGP Grünewald
7Laboratory for Pediatric Sarcoma Biology, Institute of Pathology of the LMU Munich, Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for TGP Grünewald
M Bohec
8NGS platform, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S Baulande
8NGS platform, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for S Baulande
I Janoueix-Lerosey
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for I Janoueix-Lerosey
J-P Vert
9Google Brain, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for J-P Vert
E Barillot
3Institut Curie, PSL Research University, INSERM, U900, Mines-ParisTech, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for E Barillot
O Delattre
1INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for O Delattre
  • For correspondence: olivier.delattre@curie.fr andrei.zinovyev@curie.fr
A Zinovyev
3Institut Curie, PSL Research University, INSERM, U900, Mines-ParisTech, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for A Zinovyev
  • For correspondence: olivier.delattre@curie.fr andrei.zinovyev@curie.fr
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Summary

EWSR1-FLI1, the chimeric oncogene specific for Ewing sarcoma (EwS), induces a cascade of signaling events leading to cell transformation. However, it remains elusive how genetically homogeneous EwS cells can drive heterogeneity of transcriptional programs. Here, we combined independent component analysis of single cell RNA-sequencing data from diverse cell types and model systems with time-resolved mapping of EWSR1-FLI1 binding sites and of open chromatin regions to characterize dynamic cellular processes associated with EWSR1-FLI1 activity. We thus defined an exquisitely specific and direct, super-enhancer-driven EWSR1-FLI1 program. In EwS tumors, cell proliferation was associated with a well-defined range of EWSR1-FLI1 activity; moreover, cells with a high EWSR1-FLI1 activity presented a strong oxidative phosphorylation metabolism. In contrast, a subpopulation of cells from below and above optimal EWSR1-FLI1 activity was characterized by increased hypoxia. Overall, our study reveals sources of intratumoral heterogeneity within Ewing tumors.

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 4.0 International license.
Back to top
PreviousNext
Posted April 30, 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.
Transcriptional programs define intratumoral heterogeneity of Ewing sarcoma at single cell resolution
(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
Transcriptional programs define intratumoral heterogeneity of Ewing sarcoma at single cell resolution
M-M Aynaud, O Mirabeau, N Gruel, S Grossetête, V Boeva, S Durand, D Surdez, O Saulnier, S Zaïdi, S Gribkova, U Kairov, V Raynal, F Tirode, TGP Grünewald, M Bohec, S Baulande, I Janoueix-Lerosey, J-P Vert, E Barillot, O Delattre, A Zinovyev
bioRxiv 623710; doi: https://doi.org/10.1101/623710
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Transcriptional programs define intratumoral heterogeneity of Ewing sarcoma at single cell resolution
M-M Aynaud, O Mirabeau, N Gruel, S Grossetête, V Boeva, S Durand, D Surdez, O Saulnier, S Zaïdi, S Gribkova, U Kairov, V Raynal, F Tirode, TGP Grünewald, M Bohec, S Baulande, I Janoueix-Lerosey, J-P Vert, E Barillot, O Delattre, A Zinovyev
bioRxiv 623710; doi: https://doi.org/10.1101/623710

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 (3688)
  • Biochemistry (7788)
  • Bioengineering (5674)
  • Bioinformatics (21277)
  • Biophysics (10574)
  • Cancer Biology (8173)
  • Cell Biology (11936)
  • Clinical Trials (138)
  • Developmental Biology (6762)
  • Ecology (10401)
  • Epidemiology (2065)
  • Evolutionary Biology (13861)
  • Genetics (9707)
  • Genomics (13066)
  • Immunology (8139)
  • Microbiology (19983)
  • Molecular Biology (7841)
  • Neuroscience (43049)
  • Paleontology (319)
  • Pathology (1279)
  • Pharmacology and Toxicology (2258)
  • Physiology (3351)
  • Plant Biology (7229)
  • Scientific Communication and Education (1311)
  • Synthetic Biology (2000)
  • Systems Biology (5534)
  • Zoology (1128)