{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:44:12Z","timestamp":1768347852315,"version":"3.49.0"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,1,21]],"date-time":"2016-01-21T00:00:00Z","timestamp":1453334400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,1,21]],"date-time":"2016-01-21T00:00:00Z","timestamp":1453334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cancers contain a wide diversity of cell types that are defined by differentiation states, genetic mutations and altered epigenetic programmes that impart functional diversity to individual cells. Elevated tumour cell heterogeneity is linked with progression, therapy resistance and relapse. Yet, imaging of tumour cell heterogeneity and the hallmarks of cancer has been a technical and biological challenge. Here we develop optically clear immune-compromised <jats:italic>rag2<\/jats:italic><jats:sup><jats:italic>E450fs<\/jats:italic><\/jats:sup><jats:italic>(casper)<\/jats:italic> zebrafish for optimized cell transplantation and direct visualization of fluorescently labelled cancer cells at single-cell resolution. Tumour engraftment permits dynamic imaging of neovascularization, niche partitioning of tumour-propagating cells in embryonal rhabdomyosarcoma, emergence of clonal dominance in T-cell acute lymphoblastic leukaemia and tumour evolution resulting in elevated growth and metastasis in <jats:italic>BRAF<\/jats:italic><jats:sup><jats:italic>V600E<\/jats:italic><\/jats:sup>-driven melanoma. Cell transplantation approaches using optically clear immune-compromised zebrafish provide unique opportunities to uncover biology underlying cancer and to dynamically visualize cancer processes at single-cell resolution <jats:italic>in vivo.<\/jats:italic><\/jats:p>","DOI":"10.1038\/ncomms10358","type":"journal-article","created":{"date-parts":[[2016,1,21]],"date-time":"2016-01-21T11:32:14Z","timestamp":1453375934000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish"],"prefix":"10.1038","volume":"7","author":[{"given":"Qin","family":"Tang","sequence":"first","affiliation":[]},{"given":"John C.","family":"Moore","sequence":"additional","affiliation":[]},{"given":"Myron S.","family":"Ignatius","sequence":"additional","affiliation":[]},{"given":"In\u00eas M.","family":"Tenente","sequence":"additional","affiliation":[]},{"given":"Madeline N.","family":"Hayes","sequence":"additional","affiliation":[]},{"given":"Elaine G.","family":"Garcia","sequence":"additional","affiliation":[]},{"given":"Nora","family":"Torres Yord\u00e1n","sequence":"additional","affiliation":[]},{"given":"Caitlin","family":"Bourque","sequence":"additional","affiliation":[]},{"given":"Shuning","family":"He","sequence":"additional","affiliation":[]},{"given":"Jessica S.","family":"Blackburn","sequence":"additional","affiliation":[]},{"given":"A. Thomas","family":"Look","sequence":"additional","affiliation":[]},{"given":"Yariv","family":"Houvras","sequence":"additional","affiliation":[]},{"given":"David M.","family":"Langenau","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,1,21]]},"reference":[{"key":"BFncomms10358_CR1","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646\u2013674 (2011).","journal-title":"Cell"},{"key":"BFncomms10358_CR2","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","volume":"100","author":"D Hanahan","year":"2000","unstructured":"Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57\u201370 (2000).","journal-title":"Cell"},{"key":"BFncomms10358_CR3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.stem.2014.12.011","volume":"16","author":"M Janiszewska","year":"2015","unstructured":"Janiszewska, M. & Polyak, K. Clonal evolution in cancer: a tale of twisted twines. Cell Stem Cell 16, 11\u201312 (2015).","journal-title":"Cell Stem Cell"},{"key":"BFncomms10358_CR4","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1016\/j.molonc.2014.06.005","volume":"8","author":"RA Burrell","year":"2014","unstructured":"Burrell, R. A. & Swanton, C. Tumour heterogeneity and the evolution of polyclonal drug resistance. Mol. Oncol. 8, 1095\u20131111 (2014).","journal-title":"Mol. Oncol."},{"key":"BFncomms10358_CR5","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.molcel.2014.05.015","volume":"54","author":"H Easwaran","year":"2014","unstructured":"Easwaran, H., Tsai, H. C. & Baylin, S. B. Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance. Mol. Cell 54, 716\u2013727 (2014).","journal-title":"Mol. Cell"},{"key":"BFncomms10358_CR6","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nm.3518","volume":"20","author":"K Polyak","year":"2014","unstructured":"Polyak, K. Tumor heterogeneity confounds and illuminates: a case for Darwinian tumor evolution. Nat. Med. 20, 344\u2013346 (2014).","journal-title":"Nat. Med."},{"key":"BFncomms10358_CR7","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.celrep.2013.12.041","volume":"6","author":"V Almendro","year":"2014","unstructured":"Almendro, V. et al. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep. 6, 514\u2013527 (2014).","journal-title":"Cell Rep."},{"key":"BFncomms10358_CR8","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/ng.2891","volume":"46","author":"M Gerlinger","year":"2014","unstructured":"Gerlinger, M. et al. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nat. Genet. 46, 225\u2013233 (2014).","journal-title":"Nat. Genet."},{"key":"BFncomms10358_CR9","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1016\/j.cell.2014.02.031","volume":"156","author":"DG McFadden","year":"2014","unstructured":"McFadden, D. G. et al. Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing. Cell 156, 1298\u20131311 (2014).","journal-title":"Cell"},{"key":"BFncomms10358_CR10","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.cell.2011.11.004","volume":"147","author":"MJ Pittet","year":"2011","unstructured":"Pittet, M. J. & Weissleder, R. Intravital imaging. Cell 147, 983\u2013991 (2011).","journal-title":"Cell"},{"key":"BFncomms10358_CR11","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/nrc3742","volume":"14","author":"SI Ellenbroek","year":"2014","unstructured":"Ellenbroek, S. I. & van Rheenen, J. Imaging hallmarks of cancer in living mice. Nat. Rev. Cancer 14, 406\u2013418 (2014).","journal-title":"Nat. Rev. Cancer"},{"key":"BFncomms10358_CR12","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1038\/nmeth.1269","volume":"5","author":"D Kedrin","year":"2008","unstructured":"Kedrin, D. et al. Intravital imaging of metastatic behavior through a mammary imaging window. Nat. Methods 5, 1019\u20131021 (2008).","journal-title":"Nat. Methods"},{"key":"BFncomms10358_CR13","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ccr.2006.11.020","volume":"11","author":"C Calabrese","year":"2007","unstructured":"Calabrese, C. et al. A perivascular niche for brain tumor stem cells. Cancer Cell 11, 69\u201382 (2007).","journal-title":"Cancer Cell"},{"key":"BFncomms10358_CR14","doi-asserted-by":"publisher","first-page":"158ra145","DOI":"10.1126\/scitranslmed.3004394","volume":"4","author":"L Ritsma","year":"2012","unstructured":"Ritsma, L. et al. Intravital microscopy through an abdominal imaging window reveals a pre-micrometastasis stage during liver metastasis. Sci. Transl. Med. 4, 158ra145 (2012).","journal-title":"Sci. Transl. Med."},{"key":"BFncomms10358_CR15","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature06293","volume":"450","author":"J Livet","year":"2007","unstructured":"Livet, J. et al. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450, 56\u201362 (2007).","journal-title":"Nature"},{"key":"BFncomms10358_CR16","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.cell.2010.09.016","volume":"143","author":"HJ Snippert","year":"2010","unstructured":"Snippert, H. J. et al. Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143, 134\u2013144 (2010).","journal-title":"Cell"},{"key":"BFncomms10358_CR17","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1002\/stem.1296","volume":"31","author":"A Zomer","year":"2013","unstructured":"Zomer, A. et al. Intravital imaging of cancer stem cell plasticity in mammary tumors. Stem Cells 31, 602\u2013606 (2013).","journal-title":"Stem Cells"},{"key":"BFncomms10358_CR18","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.ccr.2012.03.043","volume":"21","author":"MS Ignatius","year":"2012","unstructured":"Ignatius, M. S. et al. In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma. Cancer Cell 21, 680\u2013693 (2012).","journal-title":"Cancer Cell"},{"key":"BFncomms10358_CR19","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.stem.2007.11.002","volume":"2","author":"RM White","year":"2008","unstructured":"White, R. M. et al. Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell 2, 183\u2013189 (2008).","journal-title":"Cell Stem Cell"},{"key":"BFncomms10358_CR20","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.ccr.2010.09.009","volume":"18","author":"H Feng","year":"2010","unstructured":"Feng, H. et al. T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell 18, 353\u2013366 (2010).","journal-title":"Cancer Cell"},{"key":"BFncomms10358_CR21","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/nmeth.1542","volume":"8","author":"JD Sander","year":"2011","unstructured":"Sander, J. D. et al. Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat. Methods 8, 67\u201369 (2011).","journal-title":"Nat. Methods"},{"key":"BFncomms10358_CR22","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1038\/nmeth.3031","volume":"11","author":"Q Tang","year":"2014","unstructured":"Tang, Q. et al. Optimized cell transplantation using adult rag2 mutant zebrafish. Nat. Methods 11, 821\u2013824 (2014).","journal-title":"Nat. Methods"},{"key":"BFncomms10358_CR23","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1126\/science.1080280","volume":"299","author":"DM Langenau","year":"2003","unstructured":"Langenau, D. M. et al. Myc-induced T cell leukemia in transgenic zebrafish. Science 299, 887\u2013890 (2003).","journal-title":"Science"},{"key":"BFncomms10358_CR24","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.ccr.2012.02.010","volume":"21","author":"S Zhu","year":"2012","unstructured":"Zhu, S. et al. Activated ALK collaborates with MYCN in neuroblastoma pathogenesis. Cancer Cell 21, 362\u2013373 (2012).","journal-title":"Cancer Cell"},{"key":"BFncomms10358_CR25","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1101\/gad.1545007","volume":"21","author":"DM Langenau","year":"2007","unstructured":"Langenau, D. M. et al. Effects of RAS on the genesis of embryonal rhabdomyosarcoma. Genes Dev. 21, 1382\u20131395 (2007).","journal-title":"Genes Dev."},{"key":"BFncomms10358_CR26","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.cub.2005.01.031","volume":"15","author":"EE Patton","year":"2005","unstructured":"Patton, E. E. et al. BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr. Biol. 15, 249\u2013254 (2005).","journal-title":"Curr. Biol."},{"key":"BFncomms10358_CR27","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/nature09806","volume":"471","author":"CJ Ceol","year":"2011","unstructured":"Ceol, C. J. et al. The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature 471, 513\u2013517 (2011).","journal-title":"Nature"},{"key":"BFncomms10358_CR28","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1016\/j.bbadis.2013.01.016","volume":"1832","author":"C Tobia","year":"2013","unstructured":"Tobia, C., Gariano, G., De Sena, G. & Presta, M. Zebrafish embryo as a tool to study tumor\/endothelial cell cross-talk. Biochim. Biophys. Acta 1832, 1371\u20131377 (2013).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFncomms10358_CR29","doi-asserted-by":"publisher","first-page":"e21768","DOI":"10.1371\/journal.pone.0021768","volume":"6","author":"C Zhao","year":"2011","unstructured":"Zhao, C. et al. A novel xenograft model in zebrafish for high-resolution investigating dynamics of neovascularization in tumors. PLoS ONE 6, e21768 (2011).","journal-title":"PLoS ONE"},{"key":"BFncomms10358_CR30","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1126\/science.1104274","volume":"307","author":"X Michalet","year":"2005","unstructured":"Michalet, X. et al. Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307, 538\u2013544 (2005).","journal-title":"Science"},{"key":"BFncomms10358_CR31","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1126\/science.1164266","volume":"322","author":"CG Mullighan","year":"2008","unstructured":"Mullighan, C. G. et al. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science 322, 1377\u20131380 (2008).","journal-title":"Science"},{"key":"BFncomms10358_CR32","doi-asserted-by":"publisher","first-page":"4384","DOI":"10.1182\/blood-2011-02-338517","volume":"118","author":"MJ Clemente","year":"2011","unstructured":"Clemente, M. J. et al. Clonal drift demonstrates unexpected dynamics of the T-cell repertoire in T-large granular lymphocyte leukemia. Blood 118, 4384\u20134393 (2011).","journal-title":"Blood"},{"key":"BFncomms10358_CR33","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1182\/blood-2012-06-430645","volume":"120","author":"NJ Bahlis","year":"2012","unstructured":"Bahlis, N. J. Darwinian evolution and tiding clones in multiple myeloma. Blood 120, 927\u2013928 (2012).","journal-title":"Blood"},{"key":"BFncomms10358_CR34","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1038\/nature10738","volume":"481","author":"L Ding","year":"2012","unstructured":"Ding, L. et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 481, 506\u2013510 (2012).","journal-title":"Nature"},{"key":"BFncomms10358_CR35","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/j.cell.2013.01.019","volume":"152","author":"DA Landau","year":"2013","unstructured":"Landau, D. A. et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 152, 714\u2013726 (2013).","journal-title":"Cell"},{"key":"BFncomms10358_CR36","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.ccr.2014.01.032","volume":"25","author":"JS Blackburn","year":"2014","unstructured":"Blackburn, J. S. et al. Clonal evolution enhances leukemia-propagating cell frequency in T cell acute lymphoblastic leukemia through Akt\/mTORC1 pathway activation. Cancer Cell 25, 366\u2013378 (2014).","journal-title":"Cancer Cell"},{"key":"BFncomms10358_CR37","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1126\/science.1196236","volume":"330","author":"C Lopez-Garcia","year":"2010","unstructured":"Lopez-Garcia, C., Klein, A. M., Simons, B. D. & Winton, D. J. Intestinal stem cell replacement follows a pattern of neutral drift. Science 330, 822\u2013825 (2010).","journal-title":"Science"},{"key":"BFncomms10358_CR38","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1126\/science.1224676","volume":"337","author":"AG Schepers","year":"2012","unstructured":"Schepers, A. G. et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337, 730\u2013735 (2012).","journal-title":"Science"},{"key":"BFncomms10358_CR39","first-page":"193","volume":"181","author":"A Barth","year":"1995","unstructured":"Barth, A., Wanek, L. A. & Morton, D. L. Prognostic factors in 1,521 melanoma patients with distant metastases. J. Am. Coll. Surg. 181, 193\u2013201 (1995).","journal-title":"J. Am. Coll. Surg."},{"key":"BFncomms10358_CR40","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1016\/S0002-9440(10)64328-3","volume":"162","author":"SS Dadras","year":"2003","unstructured":"Dadras, S. S. et al. Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival. Am. J. Pathol. 162, 1951\u20131960 (2003).","journal-title":"Am. J. Pathol."},{"key":"BFncomms10358_CR41","doi-asserted-by":"publisher","first-page":"2644","DOI":"10.1158\/1078-0432.CCR-14-2391","volume":"21","author":"RS Goswami","year":"2015","unstructured":"Goswami, R. S. et al. Hotspot mutation panel testing reveals clonal evolution in a study of 265 paired primary and metastatic tumors. Clin. Cancer Res. 21, 2644\u20132651 (2015).","journal-title":"Clin. Cancer Res."},{"key":"BFncomms10358_CR42","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/BF00046337","volume":"9","author":"M Herlyn","year":"1990","unstructured":"Herlyn, M. Human melanoma: development and progression. Cancer Metastasis Rev. 9, 101\u2013112 (1990).","journal-title":"Cancer Metastasis Rev."},{"key":"BFncomms10358_CR43","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1158\/2159-8290.CD-13-0642","volume":"4","author":"H Shi","year":"2014","unstructured":"Shi, H. et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov. 4, 80\u201393 (2014).","journal-title":"Cancer Discov."},{"key":"BFncomms10358_CR44","doi-asserted-by":"publisher","first-page":"e25294","DOI":"10.4161\/intv.25294","volume":"2","author":"A Patsialou","year":"2013","unstructured":"Patsialou, A. et al. Intravital multiphoton imaging reveals multicellular streaming as a crucial component of in vivo cell migration in human breast tumors. Intravital 2, e25294 (2013).","journal-title":"Intravital"},{"key":"BFncomms10358_CR45","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1111\/j.1365-2818.2012.03667.x","volume":"251","author":"A Dovas","year":"2013","unstructured":"Dovas, A., Patsialou, A., Harney, A. S., Condeelis, J. & Cox, D. Imaging interactions between macrophages and tumour cells that are involved in metastasis in vivo and in vitro. J. Microsc. 251, 261\u2013269 (2013).","journal-title":"J. Microsc."},{"key":"BFncomms10358_CR46","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1242\/jcs.069443","volume":"123","author":"K Stoletov","year":"2010","unstructured":"Stoletov, K. et al. Visualizing extravasation dynamics of metastatic tumor cells. J. Cell Sci. 123, 2332\u20132341 (2010).","journal-title":"J. Cell Sci."},{"key":"BFncomms10358_CR47","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/978-1-61779-797-2_2","volume":"872","author":"J Hulit","year":"2012","unstructured":"Hulit, J. et al. The use of fluorescent proteins for intravital imaging of cancer cell invasion. Methods Mol. Biol. 872, 15\u201330 (2012).","journal-title":"Methods Mol. Biol."},{"key":"BFncomms10358_CR48","doi-asserted-by":"crossref","unstructured":"Burrell, K. et al. A novel high-resolution in vivo imaging technique to study the dynamic response of intracranial structures to tumor growth and therapeutics. J. Vis. Exp. e50363 (2013).","DOI":"10.3791\/50363"},{"key":"BFncomms10358_CR49","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.celrep.2014.06.045","volume":"8","author":"A Chapman","year":"2014","unstructured":"Chapman, A. et al. Heterogeneous tumor subpopulations cooperate to drive invasion. Cell Rep. 8, 688\u2013695 (2014).","journal-title":"Cell Rep."},{"key":"BFncomms10358_CR50","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/1749-799X-5-78","volume":"5","author":"VA Siclari","year":"2010","unstructured":"Siclari, V. A. & Qin, L. Targeting the osteosarcoma cancer stem cell. J. Orthop. Surg. Res. 5, 78 (2010).","journal-title":"J. Orthop. Surg. Res."},{"key":"BFncomms10358_CR51","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/nrc2246","volume":"7","author":"RJ Gilbertson","year":"2007","unstructured":"Gilbertson, R. J. & Rich, J. N. Making a tumour's bed: glioblastoma stem cells and the vascular niche. Nat. Rev. Cancer 7, 733\u2013736 (2007).","journal-title":"Nat. Rev. Cancer"},{"key":"BFncomms10358_CR52","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/nature10933","volume":"486","author":"SP Shah","year":"2012","unstructured":"Shah, S. P. et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 486, 395\u2013399 (2012).","journal-title":"Nature"},{"key":"BFncomms10358_CR53","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/nature10983","volume":"486","author":"C Curtis","year":"2012","unstructured":"Curtis, C. et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486, 346\u2013352 (2012).","journal-title":"Nature"},{"key":"BFncomms10358_CR54","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1038\/nature09515","volume":"467","author":"S Yachida","year":"2010","unstructured":"Yachida, S. et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467, 1114\u20131117 (2010).","journal-title":"Nature"},{"key":"BFncomms10358_CR55","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/nature09460","volume":"467","author":"PJ Campbell","year":"2010","unstructured":"Campbell, P. J. et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 467, 1109\u20131113 (2010).","journal-title":"Nature"},{"key":"BFncomms10358_CR56","doi-asserted-by":"publisher","first-page":"4009","DOI":"10.1073\/pnas.1219747110","volume":"110","author":"A Sottoriva","year":"2013","unstructured":"Sottoriva, A. et al. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc. Natl Acad. Sci. USA 110, 4009\u20134014 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms10358_CR57","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/nature13556","volume":"514","author":"A Marusyk","year":"2014","unstructured":"Marusyk, A. et al. Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity. Nature 514, 54\u201358 (2014).","journal-title":"Nature"},{"key":"BFncomms10358_CR58","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/sj.neo.7900121","volume":"2","author":"A Rehemtulla","year":"2000","unstructured":"Rehemtulla, A. et al. Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging. Neoplasia 2, 491\u2013495 (2000).","journal-title":"Neoplasia"},{"key":"BFncomms10358_CR59","doi-asserted-by":"publisher","first-page":"2128","DOI":"10.1016\/S0959-8049(02)00410-0","volume":"38","author":"M Edinger","year":"2002","unstructured":"Edinger, M. et al. Advancing animal models of neoplasia through in vivo bioluminescence imaging. Eur. J. Cancer 38, 2128\u20132136 (2002).","journal-title":"Eur. J. Cancer"},{"key":"BFncomms10358_CR60","first-page":"631","volume":"54","author":"A Sato","year":"2004","unstructured":"Sato, A., Klaunberg, B. & Tolwani, R. In vivo bioluminescence imaging. Comp. Med. 54, 631\u2013634 (2004).","journal-title":"Comp. Med."},{"key":"BFncomms10358_CR61","doi-asserted-by":"publisher","first-page":"610, 612, 614","DOI":"10.2144\/000112619","volume":"43","author":"ND Meeker","year":"2007","unstructured":"Meeker, N. D., Hutchinson, S. A., Ho, L. & Trede, N. S. Method for isolation of PCR-ready genomic DNA from zebrafish tissues. Biotechniques 43, 610, 612, 614 (2007).","journal-title":"Biotechniques"},{"key":"BFncomms10358_CR62","doi-asserted-by":"publisher","first-page":"3119","DOI":"10.1242\/dev.048785","volume":"137","author":"Y Wang","year":"2010","unstructured":"Wang, Y. et al. Moesin1 and Ve-cadherin are required in endothelial cells during in vivo tubulogenesis. Development 137, 3119\u20133128 (2010).","journal-title":"Development"},{"key":"BFncomms10358_CR63","doi-asserted-by":"publisher","first-page":"3296","DOI":"10.1182\/blood-2009-10-246488","volume":"115","author":"AC Smith","year":"2010","unstructured":"Smith, A. C. et al. High-throughput cell transplantation establishes that tumor-initiating cells are abundant in zebrafish T-cell acute lymphoblastic leukemia. Blood 115, 3296\u20133303 (2010).","journal-title":"Blood"},{"key":"BFncomms10358_CR64","doi-asserted-by":"publisher","first-page":"4242","DOI":"10.1038\/onc.2008.56","volume":"27","author":"DM Langenau","year":"2008","unstructured":"Langenau, D. M. et al. Co-injection strategies to modify radiation sensitivity and tumor initiation in transgenic Zebrafish. Oncogene 27, 4242\u20134248 (2008).","journal-title":"Oncogene"},{"key":"BFncomms10358_CR65","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1073\/pnas.0406252102","volume":"102","author":"S Berghmans","year":"2005","unstructured":"Berghmans, S. et al. tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors. Proc. Natl Acad. Sci. USA 102, 407\u2013412 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms10358_CR66","doi-asserted-by":"crossref","unstructured":"Blackburn, J. S., Liu, S. & Langenau, D. M. Quantifying the frequency of tumor-propagating cells using limiting dilution cell transplantation in syngeneic zebrafish. J. Vis. Exp. e2790 (2011).","DOI":"10.3791\/2790"},{"key":"BFncomms10358_CR67","doi-asserted-by":"crossref","unstructured":"Tenente, I. M., Tang, Q., Moore, J. C. & Langenau, D. M. Normal and malignant muscle cell transplantation into immune compromised adult zebrafish. J. Vis. Exp. e52597 (2014).","DOI":"10.3791\/52597"},{"key":"BFncomms10358_CR68","doi-asserted-by":"crossref","unstructured":"Pugach, E. K., Li, P., White, R. & Zon, L. Retro-orbital injection in adult zebrafish. J. Vis. Exp. e1645 (2009).","DOI":"10.3791\/1645"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms10358.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms10358","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms10358.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T11:55:41Z","timestamp":1672833341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms10358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,21]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,4,22]]}},"alternative-id":["BFncomms10358"],"URL":"https:\/\/doi.org\/10.1038\/ncomms10358","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,21]]},"assertion":[{"value":"20 April 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10358"}}