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© Research
Publication : Cell reports

Transcriptional Programs Define Intratumoral Heterogeneity of Ewing Sarcoma at Single-Cell Resolution.

Team: Brain-immune communication
Team: Expertise group: GORE – Genome Organization Regulation and Expression
Team: Bioinformatics and Biostatistics HUB
Member: Olivier Mirabeau
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell reports - 11 Feb 2020

Aynaud MM, Mirabeau O, Gruel N, Grossetête S, Boeva V, Durand S, Surdez D, Saulnier O, Zaïdi S, Gribkova S, Fouché A, Kairov U, Raynal V, Tirode F, Grünewald TGP, Bohec M, Baulande S, Janoueix-Lerosey I, Vert JP, Barillot E, Delattre O, Zinovyev A,

Link to Pubmed [PMID] – 32049009

Link to DOI – 10.1016/j.celrep.2020.01.049S2211-1247(20)30074-7

Cell Rep 2020 Feb; 30(6): 1767-1779.e6

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 the heterogeneity of transcriptional programs. Here, we combine 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 define an exquisitely specific and direct enhancer-driven EWSR1-FLI1 program. In EwS tumors, cell proliferation and strong oxidative phosphorylation metabolism are associated with a well-defined range of EWSR1-FLI1 activity. In contrast, a subpopulation of cells from below and above the intermediary EWSR1-FLI1 activity is characterized by increased hypoxia. Overall, our study reveals sources of intratumoral heterogeneity within EwS tumors.

https://pubmed.ncbi.nlm.nih.gov/32049009