Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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.
Complete list of metadatas

Cited literature [67 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-02972224
Contributor : Andrei Zinovyev <>
Submitted on : Tuesday, October 20, 2020 - 11:33:25 AM
Last modification on : Thursday, January 14, 2021 - 3:14:13 PM
Long-term archiving on: : Thursday, January 21, 2021 - 6:51:39 PM

File

Aynaud2020CellReports.pdf
Publisher files allowed on an open archive

Identifiers

Citation

Marie-Ming Aynaud, Olivier Mirabeau, Nadege Gruel, Sandrine Grossetête, Valentina Boeva, et al.. Transcriptional Programs Define Intratumoral Heterogeneity of Ewing Sarcoma at Single-Cell Resolution. Cell Reports, Elsevier Inc, 2020, 30 (6), pp.1767-1779.e6. ⟨10.1016/j.celrep.2020.01.049⟩. ⟨hal-02972224⟩

Share

Metrics

Record views

103

Files downloads

152