المؤلفون: Zhang, Haoran, Hunter, Miranda V., Chou, Jacqueline, Quinn, Jeffrey F., Zhou, Mingyuan, White, Richard M., Tansey, Wesley

المصدر: Cell Systems ; volume 14, issue 7, page 605-619.e7 ; ISSN 2405-4712

مصطلحات موضوعية: Cell Biology, Histology, Pathology and Forensic Medicine

الإتاحة: https://doi.org/10.1016/j.cels.2023.06.003Test
https://api.elsevier.com/content/article/PII:S2405471223001564?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2405471223001564?httpAccept=text/plainTest

المؤلفون: Weiss, Joshua M., Hunter, Miranda V., Cruz, Nelly M., Baggiolini, Arianna, Tagore, Mohita, Ma, Yilun, Misale, Sandra, Marasco, Michelangelo, Simon-Vermot, Theresa, Campbell, Nathaniel R., Newell, Felicity, Wilmott, James S., Johansson, Peter A., Thompson, John F., Long, Georgina V., Pearson, John V., Mann, Graham J., Scolyer, Richard A., Waddell, Nicola, Montal, Emily D., Huang, Ting Hsiang, Jonsson, Philip, Donoghue, Mark T.A., Harris, Christopher C., Taylor, Barry S., Xu, Tianhao, Chaligné, Ronan, Shliaha, Pavel V., Hendrickson, Ronald, Jungbluth, Achim A., Lezcano, Cecilia, Koche, Richard, Studer, Lorenz, Ariyan, Charlotte E., Solit, David B., Wolchok, Jedd D., Merghoub, Taha, Rosen, Neal, Hayward, Nicholas K., White, Richard M.

المصدر: Weiss , J M , Hunter , M V , Cruz , N M , Baggiolini , A , Tagore , M , Ma , Y , Misale , S , Marasco , M , Simon-Vermot , T , Campbell , N R , Newell , F , Wilmott , J S , Johansson , P A , Thompson , J F , Long , G V , Pearson , J V , Mann , G J , Scolyer , R A , Waddell , N , Montal , E D , Huang , T H , Jonsson , ....

مصطلحات موضوعية: Animals, Genetically Modified, Carcinogenesis/genetics, Foot, Hand, Humans, Melanoma/pathology, Nails, Oncogenes/genetics, Skin Neoplasms/genetics, Transcription, Genetic, Zebrafish/genetics

الوصف: Oncogenic alterations to DNA are not transforming in all cellular contexts 1,2 . This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails 3 . We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma and enrichment for CRKL amplifications in acral melanoma. We modelled these changes in transgenic zebrafish models and found that CRKL-driven tumours formed predominantly in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin and limb melanocytes, when compared with body melanocytes, revealed a positional identity gene programme typified by posterior HOX13 genes. This positional gene programme synergized with CRKL to amplify insulin-like growth factor (IGF) signalling and drive tumours at acral sites. Abrogation of this CRKL-driven programme eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.

العلاقة: https://portal.findresearcher.sdu.dk/da/publications/fc93f265-733a-47a2-81d0-e175a3bb1f60Test

الإتاحة: https://doi.org/10.1038/s41586-022-04584-6Test
https://portal.findresearcher.sdu.dk/da/publications/fc93f265-733a-47a2-81d0-e175a3bb1f60Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355078/pdf/nihms-1816756.pdfTest

المؤلفون: Perlee, Sarah, Ma, Yilun, Hunter, Miranda V, Swanson, Jacob B, Ming, Zhitao, Xia, Julia, Lionnet, Timothée, McGrail, Maura, White, Richard M

المصدر: bioRxiv

الوصف: The advent of large-scale sequencing in both development and disease has identified large numbers of candidate genes that may be linked to important phenotypes. Validating the function of these candidates in vivo is challenging, due to low efficiency and low throughput of most model systems. We have developed a rapid, scalable system for assessing the role of candidate genes using zebrafish. We generated transgenic zebrafish in which Cas9 was knocked-in to the endogenous mitfa locus, a master transcription factor of the melanocyte lineage. We used this system to identify both cell-autonomous and non-cell autonomous regulators of normal melanocyte development. We then applied this to the melanoma setting to demonstrate that loss of genes required for melanocyte survival can paradoxically promote more aggressive phenotypes, highlighting that in vitro screens can mask in vivo phenotypes. Our high-efficiency genetic approach offers a versatile tool for exploring developmental processes and disease mechanisms that can readily be applied to other cell lineages.

العلاقة: https://doi.org/10.1101/2024.03.22.586101Test; https://pubmed.ncbi.nlm.nih.gov/38562693Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983904Test/

الإتاحة: https://doi.org/10.1101/2024.03.22.586101Test
https://pubmed.ncbi.nlm.nih.gov/38562693Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983904Test/

المؤلفون: Campbell, Nathaniel, R, Rao, Anjali, Hunter, Miranda, V, Sznurkowska, Magdalena, K, Briker, Luzia, Zhang, Maomao, Baron, Maayan, Heilmann, Silja, Deforet, Maxime, Kenny, Colin, Ferretti, Lorenza, P, Huang, Ting-Hsiang, Perlee, Sarah, Garg, Manik, Nsengimana, Jérémie, Saini, Massimo, Montal, Emily, Tagore, Mohita, Newton-Bishop, Julia, Middleton, Mark, R, Corrie, Pippa, Adams, David, J, Rabbie, Roy, Aceto, Nicola, Levesque, Mitchell, P, Cornell, Robert, A, Yanai, Itai, Xavier, Joao, B, White, Richard, M

المساهمون: Laboratoire Jean Perrin (LJP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

المصدر: ISSN: 1534-5807 ; Developmental Cell ; https://cnrs.hal.science/hal-03772733Test ; Developmental Cell, 2021, 56 (20), pp.2808 - 2825.e10. ⟨10.1016/j.devcel.2021.08.018⟩.

مصطلحات موضوعية: [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology

الوصف: International audience ; Melanomas can have multiple coexisting cell states, including proliferative (PRO) versus invasive (INV) subpopulations that represent a “go or grow” trade-off; however, how these populations interact is poorly understood. Using a combination of zebrafish modeling and analysis of patient samples, we show that INV and PRO cells form spatially structured heterotypic clusters and cooperate in the seeding of metastasis, maintaining cell state heterogeneity. INV cells adhere tightly to each other and form clusters with a rim of PRO cells. Intravital imaging demonstrated cooperation in which INV cells facilitate dissemination of less metastatic PRO cells. We identified the TFAP2 neural crest transcription factor as a master regulator of clustering and PRO/INV states. Isolation of clusters from patients with metastatic melanoma revealed a subset with heterotypic PRO-INV clusters. Our data suggest a framework for the co-existence of these two divergent cell populations, in which heterotypic clusters promote metastasis via cell-cell cooperation.

العلاقة: hal-03772733; https://cnrs.hal.science/hal-03772733Test; https://cnrs.hal.science/hal-03772733/documentTest; https://cnrs.hal.science/hal-03772733/file/Campbell_Manuscript.pdfTest

الإتاحة: https://doi.org/10.1016/j.devcel.2021.08.018Test
https://cnrs.hal.science/hal-03772733Test
https://cnrs.hal.science/hal-03772733/documentTest
https://cnrs.hal.science/hal-03772733/file/Campbell_Manuscript.pdfTest

المؤلفون: Hunter, Miranda V., Moncada, Reuben, Weiss, Joshua M., Yanai, Itai, White, Richard M.

المساهمون: U.S. Department of Health & Human Services | National Institutes of Health, Pershing Square Foundation, Harry J. Lloyd Charitable Trust

المصدر: Nature Communications ; volume 12, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: During tumor progression, cancer cells come into contact with various non-tumor cell types, but it is unclear how tumors adapt to these new environments. Here, we integrate spatially resolved transcriptomics, single-cell RNA-seq, and single-nucleus RNA-seq to characterize tumor-microenvironment interactions at the tumor boundary. Using a zebrafish model of melanoma, we identify a distinct “interface” cell state where the tumor contacts neighboring tissues. This interface is composed of specialized tumor and microenvironment cells that upregulate a common set of cilia genes, and cilia proteins are enriched only where the tumor contacts the microenvironment. Cilia gene expression is regulated by ETS-family transcription factors, which normally act to suppress cilia genes outside of the interface. A cilia-enriched interface is conserved in human patient samples, suggesting it is a conserved feature of human melanoma. Our results demonstrate the power of spatially resolved transcriptomics in uncovering mechanisms that allow tumors to adapt to new environments.

الإتاحة: https://doi.org/10.1038/s41467-021-26614-zTest
https://www.nature.com/articles/s41467-021-26614-z.pdfTest
https://www.nature.com/articles/s41467-021-26614-zTest

المؤلفون: Baron, Maayan, Tagore, Mohita, Hunter, Miranda V., Kim, Isabella S., Moncada, Reuben, Yan, Yun, Campbell, Nathaniel R., White, Richard M., Yanai, Itai

المساهمون: NYU Langone Medical Center, Memorial Sloan-Kettering Cancer Center

المصدر: Cell Systems ; volume 11, issue 5, page 536-546.e7 ; ISSN 2405-4712

مصطلحات موضوعية: Cell Biology, Histology, Pathology and Forensic Medicine

الإتاحة: https://doi.org/10.1016/j.cels.2020.08.018Test
https://api.elsevier.com/content/article/PII:S240547122030329X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S240547122030329X?httpAccept=text/plainTest

المؤلفون: Hunter, Miranda V., Willoughby, Patrick Morley, Bruce, Ashley E.E., Fernandez-Gonzalez, Rodrigo

المساهمون: Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation, Ontario Ministry of Economic Development and Innovation, Ted Rogers Centre for Heart Research TBEP Seed Program, Canadian Institutes of Health Research

المصدر: Developmental Cell ; volume 47, issue 3, page 377-387.e4 ; ISSN 1534-5807

مصطلحات موضوعية: Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology

الإتاحة: https://doi.org/10.1016/j.devcel.2018.10.013Test
https://api.elsevier.com/content/article/PII:S1534580718308347?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1534580718308347?httpAccept=text/plainTest

المؤلفون: Wang, Michael F Z, Hunter, Miranda V, Wang, Gang, McFaul, Christopher, Yip, Christopher M, Fernandez-Gonzalez, Rodrigo

مصطلحات موضوعية: Image analysis, Machine learning, Time-lapse, microscopy, Morphogenesis, oriented cell division, Laser ablation

الوصف: Embryos extend their anterior-posterior (AP) axis in a conserved process known as axis elongation. Drosophila axis elongation occurs in an epithelial monolayer, the germband, and is driven by cell intercalation, cell shape changes, and oriented cell divisions at the posterior germband. Anterior germband cells also divide during axis elongation. We developed image analysis and pattern-recognition methods to track dividing cells from confocal microscopy movies in a generally applicable approach. Mesectoderm cells, forming the ventral midline, divided parallel to the AP axis, while lateral cells displayed a uniform distribution of division orientations. Mesectoderm cells did not intercalate and sustained increased AP strain before cell division. After division, mesectoderm cell density increased along the AP axis, thus relieving strain. We used laser ablation to isolate mesectoderm cells from the influence of other tissues. Uncoupling the mesectoderm from intercalating cells did not affect cell division orientation. Conversely, separating the mesectoderm from the anterior and posterior poles of the embryo resulted in uniformly oriented divisions. Our data suggest that mesectoderm cells align their division angle to reduce strain caused by mechanical forces along the AP axis of the embryo. ; This work was funded by the Ontario Ministry of Economic Development and Innovation (ER14-10-170 to R.F.-G.); the Natural Sciences and Engineering Research Council of Canada (418438-13 to R.F.-G., RGPIN-2015-043 to C.M.Y., PGS-D to M.V.H., CGS-M to C.M.); the Canada Foundation for Innovation (30279 to R.F.-G.); and the Canada First Research Excellence Fund-University of Toronto Medicine by Design (to R.F.-G. and C.M.Y.).

العلاقة: Wang, M. F., Hunter, M. V., Wang, G., McFaul, C., Yip, C. M., & Fernandez-Gonzalez, R. (2017). Automated cell tracking identifies mechanically oriented cell divisions during Drosophila axis elongation. Development, 144(7), 1350-1361.; http://hdl.handle.net/1807/88946Test

الإتاحة: https://doi.org/10.1242/dev.141473Test
http://hdl.handle.net/1807/88946Test

المؤلفون: Hunter, Miranda V, Lee, Donghoon M, Harris, Tony J C, Fernandez-Gonzalez, Rodrigo

الوصف: Embryonic epithelia have a remarkable ability to rapidly repair wounds. A supracellular actomyosin cable around the wound coordinates cellular movements and promotes wound closure. Actomyosin cable formation is accompanied by junctional rearrangements at the wound margin. We used in vivo time-lapse quantitative microscopy to show that clathrin, dynamin, and the ADP-ribosylation factor 6, three components of the endocytic machinery, accumulate around wounds in Drosophila melanogaster embryos in a process that requires calcium signaling and actomyosin contractility. Blocking endocytosis with pharmacological or genetic approaches disrupted wound repair. The defect in wound closure was accompanied by impaired removal of E-cadherin from the wound edge and defective actomyosin cable assembly. E-cadherin overexpression also resulted in reduced actin accumulation around wounds and slower wound closure. Reducing E-cadherin levels in embryos in which endocytosis was blocked rescued actin localization to the wound margin. Our results demonstrate a central role for endocytosis in wound healing and indicate that polarized E-cadherin endocytosis is necessary for actomyosin remodeling during embryonic wound repair. ; This work was supported by a Connaught Fund New Investigator Award to R. Fernandez-Gonzalez and grants from the University of Toronto Faculty of Medicine Dean’s New Staff Fund, the Canada Foundation for Innovation (#30279), and the Natural Sciences and Engineering Research Council of Canada Discovery Grant program (#418438-13) to R. Fernandez-Gonzalez.

العلاقة: Hunter, M.V., Lee, D.M., Harris, T.J. and Fernandez-Gonzalez, R., 2015. Polarized E-cadherin endocytosis directs actomyosin remodeling during embryonic wound repair. J Cell Biol, 210(5), pp.801-816.; http://hdl.handle.net/1807/89955Test

الإتاحة: https://doi.org/10.1083/jcb.201501076Test
http://hdl.handle.net/1807/89955Test

المؤلفون: Baggiolini, Arianna, Callahan, Scott J., Montal, Emily, Weiss, Joshua M., Trieu, Tuan, Tagore, Mohita M., Tischfield, Sam E., Walsh, Ryan M., Suresh, Shruthy, Fan, Yujie, Campbell, Nathaniel R., Perlee, Sarah C., Saurat, Nathalie, Hunter, Miranda V., Simon-Vermot, Theresa, Huang, Ting-Hsiang, Ma, Yilun, Hollmann, Travis, Tickoo, Satish K., Taylor, Barry S., Khurana, Ekta, Koche, Richard P., Studer, Lorenz, White, Richard M.

المصدر: Science ; volume 373, issue 6559 ; ISSN 0036-8075 1095-9203

الوصف: Chromatin state and oncogenic competence Although specific DNA mutations can lead to tumor generation, they are not transforming in all cellular contexts. This may be due to the intrinsic transcriptional program present in the cell of origin. Using zebrafish and human pluripotent stem cell cancer models, Baggiolini et al . report that neural crest cells and melanoblasts (precursors to melanocytes) are susceptible to specific mutation of the BRAF gene, whereas melanocytes are relatively resistant (see the Perspective by Vredevoogd and Peeper). The competent cells display higher levels of chromatin factors such as the protein ATAD2 compared with the less competent ones. ATAD2 forms a complex with the neural crest transcription factor SOX10 and establishes a chromatin state that makes them permissive to BRAF mutagenesis. These data indicate that developmental chromatin programs are a determinant of how cells respond to DNA mutations. —BAP

الإتاحة: https://doi.org/10.1126/science.abc1048Test