دورية أكاديمية
Single-cell profiling of alveolar rhabdomyosarcoma reveals RAS pathway inhibitors as cell-fate hijackers with therapeutic relevance
| العنوان: | Single-cell profiling of alveolar rhabdomyosarcoma reveals RAS pathway inhibitors as cell-fate hijackers with therapeutic relevance |
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| المؤلفون: | Danielli, S.G., Porpiglia, E., De Micheli, A.J., Navarro, N., Zellinger, M.J., Bechtold, I., Kisele, S., Volken, L., Marques, J.G., Kasper, S., Bode, P.K., Henssen, A.G., Gürgen, D., Delattre, O., Surdez, D., Roma, J., Bühlmann, P., Blau, H.M., Wachtel, M., Schäfer, B.W. |
| بيانات النشر: | American Association for the Advancement of Science |
| سنة النشر: | 2023 |
| المجموعة: | Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
| مصطلحات موضوعية: | Cancer Research |
| الوصف: | Rhabdomyosarcoma (RMS) is a group of pediatric cancers with features of developing skeletal muscle. The cellular hierarchy and mechanisms leading to developmental arrest remain elusive. Here, we combined single-cell RNA sequencing, mass cytometry, and high-content imaging to resolve intratumoral heterogeneity of patient-derived primary RMS cultures. We show that the aggressive alveolar RMS (aRMS) subtype contains plastic muscle stem-like cells and cycling progenitors that drive tumor growth, and a subpopulation of differentiated cells that lost its proliferative potential and correlates with better outcomes. While chemotherapy eliminates cycling progenitors, it enriches aRMS for muscle stem-like cells. We screened for drugs hijacking aRMS toward clinically favorable subpopulations and identified a combination of RAF and MEK inhibitors that potently induces myogenic differentiation and inhibits tumor growth. Overall, our work provides insights into the developmental states underlying aRMS aggressiveness, chemoresistance, and progression and identifies the RAS pathway as a promising therapeutic target. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; other |
| اللغة: | English |
| العلاقة: | http://edoc.mdc-berlin.de/23121/1/23121oa.pdfTest; http://edoc.mdc-berlin.de/23121/6/23121suppl.zipTest; Single-cell profiling of alveolar rhabdomyosarcoma reveals RAS pathway inhibitors as cell-fate hijackers with therapeutic relevance. Danielli, S.G. and Porpiglia, E. and De Micheli, A.J. and Navarro, N. and Zellinger, M.J. and Bechtold, I. and Kisele, S. and Volken, L. and Marques, J.G. and Kasper, S. and Bode, P.K. and Henssen, A.G. and Gürgen, D. and Delattre, O. and Surdez, D. and Roma, J. and Bühlmann, P. and Blau, H.M. and Wachtel, M. and Schäfer, B.W. Science Advances 9 (6): eade9238. 10 February 2023 |
| DOI: | 10.1126/sciadv.ade9238 |
| الإتاحة: | https://doi.org/10.1126/sciadv.ade9238Test http://edoc.mdc-berlin.de/23121Test/ https://edoc.mdc-berlin.de/23121Test/ http://edoc.mdc-berlin.de/23121/1/23121oa.pdfTest http://edoc.mdc-berlin.de/23121/6/23121suppl.zipTest |
| حقوق: | cc_by_4 |
| رقم الانضمام: | edsbas.48A774CB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1126/sciadv.ade9238 |
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