تقرير
Transcriptional programs define intratumoral heterogeneity of Ewing sarcoma at single cell resolution
| العنوان: | Transcriptional programs define intratumoral heterogeneity of Ewing sarcoma at single cell resolution |
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| المؤلفون: | Aynaud, M-M, Mirabeau, O, Gruel, N, Grossetête, S, Boeva, V, Durand, S, Surdez, D, Saulnier, O, Zaïdi, S, Gribkova, S, Kairov, U, Raynal, V, Tirode, F, Grünewald, TGP, Bohec, M, Baulande, S, Janoueix-Lerosey, I, Vert, J-P, Barillot, E, Delattre, O, Zinovyev, A |
| سنة النشر: | 2019 |
| المجموعة: | Zenodo |
| مصطلحات موضوعية: | Single-cell RNA-sequencing, Ewing sarcoma, intratumor heterogeneity, Patient Derived Xenografts, transcriptional factor, histone marks, Independent Component Analysis |
| الوصف: | 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. |
| نوع الوثيقة: | report |
| اللغة: | English |
| العلاقة: | info:eu-repo/grantAgreement/EC/H2020/826121/; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130025Test; https://zenodo.org/communities/ipcTest; https://zenodo.org/record/3518847Test; https://doi.org/10.1101/623710Test; oai:zenodo.org:3518847 |
| DOI: | 10.1101/623710 |
| الإتاحة: | https://doi.org/10.1101/623710Test https://zenodo.org/record/3518847Test |
| حقوق: | info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by/4.0/legalcodeTest |
| رقم الانضمام: | edsbas.1D5E8B7B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1101/623710 |
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