دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Transcriptional Programs Define Intratumoral Heterogeneity of Ewing Sarcoma at Single-Cell Resolution.
المؤلفون: Aynaud MM; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Mirabeau O; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Gruel N; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France; Institut Curie, PSL Research University, Department of Translational Research, 75005 Paris, France., Grossetête S; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Boeva V; Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes UMR-S1016, 75014 Paris, France; Department of Computer Science, Institute for Machine Learning, Swiss Institute of Bioinformatics (SIB), ETH Zurich, 8092 Zurich, Switzerland; INSERM U900, 75005 Paris, France; Mines ParisTech, PSL Research University, CBIO-Centre for Computational Biology, 75006 Paris, France; Institut Curie, PSL Research University, 75005 Paris, France., Durand S; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Surdez D; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Saulnier O; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Zaïdi S; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Gribkova S; INSERM U900, 75005 Paris, France; Mines ParisTech, PSL Research University, CBIO-Centre for Computational Biology, 75006 Paris, France; Institut Curie, PSL Research University, 75005 Paris, France; Université Denis Diderot, 75013, Paris, France., Fouché A; École Normale Supérieure Paris-Saclay, 94230 Cachan, France., Kairov U; Laboratory of Bioinformatics and Systems Biology, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan., Raynal V; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Tirode F; University of Lyon, Université Claude Bernard Lyon 1, CNRS 5286, INSERM U1052, Cancer Research Centre of Lyon, 69008 Lyon, France., Grünewald TGP; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France; Institut Curie, PSL Research University, Department of Translational Research, 75005 Paris, France., Bohec M; NGS Platform, Institut Curie, 75005 Paris, France., Baulande S; NGS Platform, Institut Curie, 75005 Paris, France., Janoueix-Lerosey I; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Vert JP; Mines ParisTech, PSL Research University, CBIO-Centre for Computational Biology, 75006 Paris, France; Google Research, Brain Team, 75009 Paris, France., Barillot E; INSERM U900, 75005 Paris, France; Mines ParisTech, PSL Research University, CBIO-Centre for Computational Biology, 75006 Paris, France; Institut Curie, PSL Research University, 75005 Paris, France., Delattre O; INSERM U830, Équipe Labellisée LNCC, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France. Electronic address: olivier.delattre@curie.fr., Zinovyev A; INSERM U900, 75005 Paris, France; Mines ParisTech, PSL Research University, CBIO-Centre for Computational Biology, 75006 Paris, France; Institut Curie, PSL Research University, 75005 Paris, France. Electronic address: andrei.zinovyev@curie.fr.
المصدر: Cell reports [Cell Rep] 2020 Feb 11; Vol. 30 (6), pp. 1767-1779.e6.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, c 2012-
مواضيع طبية MeSH: Gene Expression Regulation, Neoplastic/*genetics , RNA-Binding Protein EWS/*metabolism , Sarcoma, Ewing/*genetics , Transcription, Genetic/*genetics, Cell Line, Tumor ; Humans ; Signal Transduction
مستخلص: 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.
Competing Interests: Declaration of Interests The authors declare no competing interests.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: EWSR1-FLI1; Ewing sarcoma; Independent Component Analysis; intratumor heterogeneity; patient-derived xenografts; single-cell RNA-sequencing; time series; transcriptomics
المشرفين على المادة: 0 (EWSR1 protein, human)
0 (RNA-Binding Protein EWS)
تواريخ الأحداث: Date Created: 20200213 Date Completed: 20210308 Latest Revision: 20210308
رمز التحديث: 20221213
DOI: 10.1016/j.celrep.2020.01.049
PMID: 32049009
قاعدة البيانات: MEDLINE
الوصف
تدمد:2211-1247
DOI:10.1016/j.celrep.2020.01.049