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| DOI | 10.1038/S41586-022-05242-7 | ||||
| Año | 2022 | ||||
| Tipo | artículo de investigación |
Citas Totales
Autores Afiliación Chile
Instituciones Chile
% Participación
Internacional
Autores
Afiliación Extranjera
Instituciones
Extranjeras
Although melanoma is notorious for its high degree of heterogeneity and plasticity1,2, the origin and magnitude of cell-state diversity remains poorly understood. Equally, it is unclear whether growth and metastatic dissemination are supported by overlapping or distinct melanoma subpopulations. Here, by combining mouse genetics, single-cell and spatial transcriptomics, lineage tracing and quantitative modelling, we provide evidence of a hierarchical model of tumour growth that mirrors the cellular and molecular logic underlying the cell-fate specification and differentiation of the embryonic neural crest. We show that tumorigenic competence is associated with a spatially localized perivascular niche, a phenotype acquired through an intercellular communication pathway established by endothelial cells. Consistent with a model in which only a fraction of cells are fated to fuel growth, temporal single-cell tracing of a population of melanoma cells with a mesenchymal-like state revealed that these cells do not contribute to primary tumour growth but, instead, constitute a pool of metastatic initiating cells that switch cell identity while disseminating to secondary organs. Our data provide a spatially and temporally resolved map of the diversity and trajectories of melanoma cell states and suggest that the ability to support growth and metastasis are limited to distinct pools of cells. The observation that these phenotypic competencies can be dynamically acquired after exposure to specific niche signals warrant the development of therapeutic strategies that interfere with the cancer cell reprogramming activity of such microenvironmental cues.
| Ord. | Autor | Género | Institución - País |
|---|---|---|---|
| 1 | Karras, Panagiotis | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 2 | Bordeu, Ignacio | Hombre |
Faculty of Mathematics - Reino Unido
Wellcome Trust/ Cancer Research UK Gurdon Institute - Reino Unido Universidad de Chile - Chile University of Cambridge - Reino Unido UNIV CAMBRIDGE - Reino Unido |
| 3 | Pozniak, Joanna | Mujer |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 4 | Nowosad, Ada | - |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 5 | Pazzi, Cecilia | Mujer |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 6 | Van Raemdonck, Nina | Mujer |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 7 | Landeloos, Ewout | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 8 | Van Herck, Yannick | Hombre |
KU Leuven– University Hospital Leuven - Bélgica
KU Leuven - Bélgica UZ Leuven - Bélgica |
| 9 | Pedri, Dennis | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 10 | Bervoets, Greet | Mujer |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 11 | Makhzami, Samira | Mujer |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 12 | Khoo, Jia Hui | - |
BGI-Shenzhen - China
BGI Shenzhen - China |
| 13 | Pavie, Benjamin | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
Universiteit Gent - Bélgica VIB Ctr Brain & Dis Res - Bélgica VIB Ctr Inflammat Res - Bélgica Univ Ghent - Bélgica |
| 14 | Lamote, Jochen | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
VIB - Bélgica |
| 15 | Marin-Bejar, Oskar | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 16 | Dewaele, Michael | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 17 | Liang, Han | - |
BGI-Shenzhen - China
BGI Shenzhen - China |
| 18 | Zhang, Xingju | - |
BGI-Shenzhen - China
BGI Shenzhen - China |
| 19 | Hua, Yichao | - |
KU Leuven - Bélgica
Vlaams Instituut voor Biotechnologie - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 20 | Wouters, Jasper | Hombre |
KU Leuven - Bélgica
VIB KU Leuven - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 21 | Browaeys, Robin | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
Universiteit Gent - Bélgica VIB Ctr Inflammat Res - Bélgica Univ Ghent - Bélgica |
| 22 | Bergers, Gabriele | Mujer |
KU Leuven - Bélgica
Vlaams Instituut voor Biotechnologie - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| 23 | Saeys, Yvan | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
Universiteit Gent - Bélgica VIB Ctr Inflammat Res - Bélgica Univ Ghent - Bélgica |
| 24 | Bosisio, Francesca | Mujer |
Departement Beeldvorming & Pathologie - Bélgica
KU Leuven - Bélgica Katholieke Univ Leuven - Bélgica |
| 25 | van den Oord, Joost | Hombre |
Departement Beeldvorming & Pathologie - Bélgica
KU Leuven - Bélgica Katholieke Univ Leuven - Bélgica |
| 26 | Lambrechts, Diether | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
Departement Oncologie - Bélgica VIB - Bélgica KU Leuven - Bélgica Katholieke Univ Leuven - Bélgica |
| 27 | Rustgi, Anil K. | Hombre |
Columbia University Irving Medical Center - Estados Unidos
Columbia Univ - Estados Unidos |
| 28 | Bechter, Oliver | Hombre |
KU Leuven– University Hospital Leuven - Bélgica
KU Leuven - Bélgica UZ Leuven - Bélgica |
| 29 | Blanpain, Cedric | Hombre |
Université libre de Bruxelles - Bélgica
Univ Libre Bruxelles ULB - Bélgica |
| 30 | Simons, Benjamin D. | Hombre |
Faculty of Mathematics - Reino Unido
Wellcome Trust/ Cancer Research UK Gurdon Institute - Reino Unido University of Cambridge - Reino Unido UNIV CAMBRIDGE - Reino Unido |
| 31 | Rambow, Florian | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica Universitätsklinikum Essen - Alemania Universität Duisburg-Essen - Alemania partner site Essen - Alemania VIB - Bélgica German Canc Consortium DKTK - Alemania Katholieke Univ Leuven - Bélgica Univ Hosp Essen - Alemania Univ Duisburg Essen - Alemania UZ Leuven - Bélgica German Cancer Research Center - Alemania |
| 32 | Marine, Jean Christophe | Hombre |
Vlaams Instituut voor Biotechnologie - Bélgica
KU Leuven - Bélgica VIB - Bélgica Katholieke Univ Leuven - Bélgica UZ Leuven - Bélgica |
| Fuente |
|---|
| EPSRC |
| Wellcome Trust |
| Alexander von Humboldt Foundation |
| Royal Society |
| Engineering and Physical Sciences Research Council |
| FWO |
| Stichting tegen Kanker |
| Fonds Wetenschappelijk Onderzoek |
| Alexander von Humboldt-Stiftung |
| Marie Curie |
| KU Leuven |
| Vlaams Instituut voor Biotechnologie |
| Research Foundation-Flanders (FWO) |
| Melanoma Research Alliance |
| Flemish Government, department EWI |
| Boehringer Ingelheim Fonds |
| Vlaams Supercomputer Centrum |
| Neftkens foundation |
| European Orthodontic Society |
| Belgian Excellence of Science |
| Royal Society E. P. Abraham Research Professorship |
| Marie Curie Individual Fellowship (H2020-MSCA-IF-2018) |
| KU Leuven (C1 grant) |
| VIB PhD international programme |
| Marie Curie Individual Fellowship (H2020-MSCA-IF-2019) |
| Stichting tegen Kanker (Foundation against Cancer) |
| FWO at the program under the Marie Sklodowska-Curie grant |
| FWO-SB |
| Belgian Excellence of Science (EOS) programme |
| Agradecimiento |
|---|
| We thank G. Ghanem for providing us with the MM lines; H. Clevers for providing us with the Confetti-reporter mouse strain; and O. Van Goethem and V. Benne for their assistance with the mouse experiments; the members of the VIB Technology Watch members, M. Bontinck and Y.-C. Wang, for facilitating collaborations with Resolve Biosciences and BGI research, respectively; and Y. Oren and the laboratories of A. Regev and J. Brugge for providing the watermelon vector. P.K. received financial support from an Marie Curie Individual Fellowship (H2020‐MSCA‐IF‐2018, 841092), FWO (1210520N) and Stichting tegen Kanker (Foundation against Cancer, 2021-028). J.P. received financial support from a Marie Curie Individual Fellowship (H2020‐MSCA‐IF‐2019, 896897). A.N. received postdoctoral from the KU Leuven (PDMT1/21/035). C.P. received PhD research fellowships from FWO (11M3822N) and of the Boehringer Ingelheim Fonds. J.W. received a postdoctoral research fellowship from Stichting Tegen Kanker (Foundation against Cancer; 2019-100). O.M.-B. was supported by the 12T1217N project by the FWO at the program under the Marie Skłodowska-Curie grant agreement no. 665501. D.P. and N.V.D. received PhD fellowships from the VIB PhD international programme and FWO-SB 1S79619N, respectively. F.R. acknowledges support from the Alexander von Humboldt Foundation. The computational resources and services used in this work were provided by the VSC (Flemish Supercomputer Centre), funded by the Research Foundation–Flanders (FWO) and the Flemish Government, department EWI. B.D.S. acknowledges funding from the Royal Society E. P. Abraham Research Professorship (RP\R1\180165), EPSRC (EP/P034616/1) and Wellcome Trust (219478/Z/19/Z). This work was supported by the FWO (G0C530N and G070622N), Stichting Tegen Kanker (FAF-F/2018/1265), Neftkens foundation, Melanoma Research Alliance (MRA, EIA#623591), KU Leuven (C1 grant) and the Belgian Excellence of Science (EOS) programme to J.-C.M. |
| We thank G. Ghanem for providing us with the MM lines; H. Clevers for providing us with the Confetti-reporter mouse strain; and O. Van Goethem and V. Benne for their assistance with the mouse experiments; the members of the VIB Technology Watch members, M. Bontinck and Y.-C. Wang, for facilitating collaborations with Resolve Biosciences and BGI research, respectively; and Y. Oren and the laboratories of A. Regev and J. Brugge for providing the watermelon vector. P.K. received financial support from an Marie Curie Individual Fellowship (H2020‐MSCA‐IF‐2018, 841092), FWO (1210520N) and Stichting tegen Kanker (Foundation against Cancer, 2021-028). J.P. received financial support from a Marie Curie Individual Fellowship (H2020‐MSCA‐IF‐2019, 896897). A.N. received postdoctoral from the KU Leuven (PDMT1/21/035). C.P. received PhD research fellowships from FWO (11M3822N) and of the Boehringer Ingelheim Fonds. J.W. received a postdoctoral research fellowship from Stichting Tegen Kanker (Foundation against Cancer; 2019-100). O.M.-B. was supported by the 12T1217N project by the FWO at the program under the Marie Skłodowska-Curie grant agreement no. 665501. D.P. and N.V.D. received PhD fellowships from the VIB PhD international programme and FWO-SB 1S79619N, respectively. F.R. acknowledges support from the Alexander von Humboldt Foundation. The computational resources and services used in this work were provided by the VSC (Flemish Supercomputer Centre), funded by the Research Foundation–Flanders (FWO) and the Flemish Government, department EWI. B.D.S. acknowledges funding from the Royal Society E. P. Abraham Research Professorship (RP\R1\180165), EPSRC (EP/P034616/1) and Wellcome Trust (219478/Z/19/Z). This work was supported by the FWO (G0C530N and G070622N), Stichting Tegen Kanker (FAF-F/2018/1265), Neftkens foundation, Melanoma Research Alliance (MRA, EIA#623591), KU Leuven (C1 grant) and the Belgian Excellence of Science (EOS) programme to J.-C.M. |
| We thank G. Ghanem for providing us with the MM lines; H. Clevers for providing us with the Confetti-reporter mouse strain; and O. Van Goethem and V. Benne for their assistance with the mouse experiments; the members of the VIB Technology Watch members, M. Bontinck and Y.-C. Wang, for facilitating collaborations with Resolve Biosciences and BGI research, respectively; and Y. Oren and the laboratories of A. Regev and J. Brugge for providing the watermelon vector. P.K. received financial support from an Marie Curie Individual Fellowship (H2020-MSCA-IF-2018, 841092), FWO (1210520N) and Stichting tegen Kanker (Foundation against Cancer, 2021-028). J.P. received financial support from a Marie Curie Individual Fellowship (H2020-MSCA-IF-2019, 896897). A.N. received postdoctoral from the KU Leuven (PDMT1/21/035). C.P. received PhD research fellowships from FWO (11M3822N) and of the Boehringer Ingelheim Fonds. J.W. received a postdoctoral research fellowship from Stichting Tegen Kanker (Foundation against Cancer; 2019-100). O.M.-B. was supported by the 12T1217N project by the FWO at the program under the Marie Sklodowska-Curie grant agreement no. 665501. D.P. and N.V.D. received PhD fellowships from the VIB PhD international programme and FWO-SB 1S79619N, respectively. F.R. acknowledges support from the Alexander von Humboldt Foundation. The computational resources and services used in this work were provided by the VSC (Flemish Supercomputer Centre), funded by the Research Foundation-Flanders (FWO) and the Flemish Government, department EWI. B.D.S. acknowledges funding from the Royal Society E. P. Abraham Research Professorship (RP\R1\180165), EPSRC (EP/P034616/1) and Wellcome Trust (219478/Z/19/Z). This work was supported by the FWO (G0C530N and G070622N), Stichting Tegen Kanker (FAF-F/2018/1265), Neftkens foundation, Melanoma Research Alliance (MRA, EIA#623591), KU Leuven (C1 grant) and the Belgian Excellence of Science (EOS) programme to J.-C.M. |