{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T06:56:15Z","timestamp":1794552975688,"version":"4.9.1"},"reference-count":99,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R21CA264361"],"award-info":[{"award-number":["R21CA264361"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["1F30CA257400-01"],"award-info":[{"award-number":["1F30CA257400-01"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P50 CA225450"],"award-info":[{"award-number":["P50 CA225450"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000092","name":"U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine","doi-asserted-by":"publisher","award":["R01LM013522"],"award-info":[{"award-number":["R01LM013522"]}],"id":[{"id":"10.13039\/100000092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Genet"],"published-print":{"date-parts":[[2022,8]]},"DOI":"10.1038\/s41588-022-01141-9","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T11:03:16Z","timestamp":1659697396000},"page":"1192-1201","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":544,"title":["Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment"],"prefix":"10.1038","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6537-5557","authenticated-orcid":false,"given":"Dalia","family":"Barkley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reuben","family":"Moncada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maayan","family":"Pour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Liberman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Dryg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Werba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maayan","family":"Baron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8815-9865","authenticated-orcid":false,"given":"Anjali","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0929-7253","authenticated-orcid":false,"given":"Bo","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo S.","family":"Fran\u00e7a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Weil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah F.","family":"Delair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Hajdu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda W.","family":"Lund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Osman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8438-2741","authenticated-orcid":false,"given":"Itai","family":"Yanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"1141_CR1","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":"1141_CR2","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/j.cell.2017.01.018","volume":"168","author":"N McGranahan","year":"2017","unstructured":"McGranahan, N. & Swanton, C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 168, 613\u2013628 (2017).","journal-title":"Cell"},{"key":"1141_CR3","first-page":"105","volume":"1805","author":"A Marusyk","year":"2010","unstructured":"Marusyk, A. & Polyak, K. Tumor heterogeneity: causes and consequences. Biochim. Biophys. Acta 1805, 105\u2013117 (2010).","journal-title":"Biochim. Biophys. Acta"},{"key":"1141_CR4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/BF00046903","volume":"2","author":"GH Heppner","year":"1983","unstructured":"Heppner, G. H. & Miller, B. E. Tumor heterogeneity: biological implications and therapeutic consequences. Cancer Metastasis Rev. 2, 5\u201323 (1983).","journal-title":"Cancer Metastasis Rev."},{"key":"1141_CR5","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1038\/nm.3915","volume":"21","author":"AA Alizadeh","year":"2015","unstructured":"Alizadeh, A. A. et al. Toward understanding and exploiting tumor heterogeneity. Nat. Med. 21, 846\u2013853 (2015).","journal-title":"Nat. Med."},{"key":"1141_CR6","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1126\/science.1254257","volume":"344","author":"AP Patel","year":"2014","unstructured":"Patel, A. P. et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344, 1396\u20131401 (2014).","journal-title":"Science"},{"key":"1141_CR7","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.cell.2019.06.024","volume":"178","author":"C Neftel","year":"2019","unstructured":"Neftel, C. et al. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell 178, 835\u2013849.e21 (2019).","journal-title":"Cell"},{"key":"1141_CR8","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.cels.2020.08.018","volume":"11","author":"M Baron","year":"2020","unstructured":"Baron, M. et al. The stress-like cancer cell state is a consistent component of tumorigenesis. Cell Syst. 11, 536\u2013546.e7 (2020).","journal-title":"Cell Syst."},{"key":"1141_CR9","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/s41587-019-0392-8","volume":"38","author":"R Moncada","year":"2020","unstructured":"Moncada, R. et al. Integrating microarray-based spatial transcriptomics and single-cell RNA-seq reveals tissue architecture in pancreatic ductal adenocarcinomas. Nat. Biotechnol. 38, 333\u2013342 (2020).","journal-title":"Nat. Biotechnol."},{"key":"1141_CR10","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.cell.2017.10.044","volume":"171","author":"SV Puram","year":"2017","unstructured":"Puram, S. V. et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell 171, 1611\u20131624.e24 (2017).","journal-title":"Cell"},{"key":"1141_CR11","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/j.cell.2018.03.041","volume":"173","author":"C Kim","year":"2018","unstructured":"Kim, C. et al. Chemoresistance evolution in triple-negative breast cancer delineated by single-cell sequencing. Cell 173, 879\u2013893.e13 (2018).","journal-title":"Cell"},{"key":"1141_CR12","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1038\/s41591-020-0926-0","volume":"26","author":"B Izar","year":"2020","unstructured":"Izar, B. et al. A single-cell landscape of high-grade serous ovarian cancer. Nat. Med. 26, 1271\u20131279 (2020).","journal-title":"Nat. Med."},{"key":"1141_CR13","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nature20123","volume":"539","author":"I Tirosh","year":"2016","unstructured":"Tirosh, I. et al. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature 539, 309\u2013313 (2016).","journal-title":"Nature"},{"key":"1141_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11493-2","volume":"10","author":"ZJ Reitman","year":"2019","unstructured":"Reitman, Z. J. et al. Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells. Nat. Commun. 10, 3731 (2019).","journal-title":"Nat. Commun."},{"key":"1141_CR15","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.cell.2018.06.025","volume":"174","author":"F Rambow","year":"2018","unstructured":"Rambow, F. et al. Toward minimal residual disease-directed therapy in melanoma. Cell 174, 843\u2013855.e19 (2018).","journal-title":"Cell"},{"key":"1141_CR16","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.cels.2020.08.018","volume":"11","author":"M Baron","year":"2020","unstructured":"Baron, M. et al. The stress-like cancer cell state is a consistent component of tumorigenesis. Cell Syst. 11, 536\u2013546.e7 (2020).","journal-title":"Cell Syst."},{"key":"1141_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09853-z","volume":"10","author":"A Dirkse","year":"2019","unstructured":"Dirkse, A. et al. Stem cell-associated heterogeneity in glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment. Nat. Commun. 10, 1787 (2019).","journal-title":"Nat. Commun."},{"key":"1141_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05220-6","volume":"9","author":"AS Cazet","year":"2018","unstructured":"Cazet, A. S. et al. Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer. Nat. Commun. 9, 2897 (2018).","journal-title":"Nat. Commun."},{"key":"1141_CR19","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","volume":"20","author":"D Aran","year":"2019","unstructured":"Aran, D. et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat. Immunol. 20, 163\u2013172 (2019).","journal-title":"Nat. Immunol."},{"key":"1141_CR20","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00776-9","volume":"12","author":"W Lin","year":"2020","unstructured":"Lin, W. et al. Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions. Genome Med. 12, 80 (2020).","journal-title":"Genome Med."},{"key":"1141_CR21","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.cell.2020.08.040","volume":"183","author":"A Sharma","year":"2020","unstructured":"Sharma, A. et al. Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in hepatocellular carcinoma. Cell 183, 377\u2013394.e21 (2020).","journal-title":"Cell"},{"key":"1141_CR22","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.jhep.2020.05.039","volume":"73","author":"M Zhang","year":"2020","unstructured":"Zhang, M. et al. Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma. J. Hepatol. 73, 1118\u20131130 (2020).","journal-title":"J. Hepatol."},{"key":"1141_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16164-1","volume":"11","author":"N Kim","year":"2020","unstructured":"Kim, N. et al. Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma. Nat. Commun. 11, 2285 (2020).","journal-title":"Nat. Commun."},{"key":"1141_CR24","first-page":"1661","volume":"182","author":"AL Ji","year":"2020","unstructured":"Ji, A. L. et al. Multimodal analysis of composition and spatial architecture in human squamous. Cell Carcinoma Cell 182, 1661\u20131662 (2020).","journal-title":"Cell Carcinoma Cell"},{"key":"1141_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41540-017-0038-8","volume":"4","author":"L Cantini","year":"2018","unstructured":"Cantini, L. et al. Classification of gene signatures for their information value and functional redundancy. NPJ Syst. Biol. Appl. 4, 2 (2018).","journal-title":"NPJ Syst. Biol. Appl"},{"key":"1141_CR26","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.ccell.2020.01.003","volume":"37","author":"Z Hu","year":"2020","unstructured":"Hu, Z. et al. The repertoire of serous ovarian cancer non-genetic heterogeneity revealed by single-cell sequencing of normal fallopian tube epithelial cells. Cancer Cell 37, 226\u2013242.e7 (2020).","journal-title":"Cancer Cell"},{"key":"1141_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04334-1","volume":"9","author":"QH Nguyen","year":"2018","unstructured":"Nguyen, Q. H. et al. Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity. Nat. Commun. 9, 2028 (2018).","journal-title":"Nat. Commun."},{"key":"1141_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06318-7","volume":"9","author":"SA MacParland","year":"2018","unstructured":"MacParland, S. A. et al. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat. Commun. 9, 4383 (2018).","journal-title":"Nat. Commun."},{"key":"1141_CR29","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1126\/science.aad0501","volume":"352","author":"I Tirosh","year":"2016","unstructured":"Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189\u2013196 (2016).","journal-title":"Science"},{"key":"1141_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01174-3","volume":"8","author":"SW Brady","year":"2017","unstructured":"Brady, S. W. et al. Combating subclonal evolution of resistant cancer phenotypes. Nat. Commun. 8, 1231 (2017).","journal-title":"Nat. Commun."},{"key":"1141_CR31","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/s41573-018-0011-2","volume":"18","author":"EC Borden","year":"2019","unstructured":"Borden, E. C. Interferons \u03b1 and \u03b2 in cancer: therapeutic opportunities from new insights. Nat. Rev. Drug Discov. 18, 219\u2013234 (2019).","journal-title":"Nat. Rev. Drug Discov."},{"key":"1141_CR32","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/ni1213","volume":"6","author":"GP Dunn","year":"2005","unstructured":"Dunn, G. P. et al. A critical function for type I interferons in cancer immunoediting. Nat. Immunol. 6, 722\u2013729 (2005).","journal-title":"Nat. Immunol."},{"key":"1141_CR33","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/nrc.2016.14","volume":"16","author":"BS Parker","year":"2016","unstructured":"Parker, B. S., Rautela, J. & Hertzog, P. J. Antitumour actions of interferons: implications for cancer therapy. Nat. Rev. Cancer 16, 131\u2013144 (2016).","journal-title":"Nat. Rev. Cancer"},{"key":"1141_CR34","doi-asserted-by":"publisher","first-page":"333","DOI":"10.3389\/fimmu.2019.00333","volume":"10","author":"AE Vilgelm","year":"2019","unstructured":"Vilgelm, A. E. & Richmond, A. Chemokines modulate immune surveillance in tumorigenesis, metastasis, and response to immunotherapy. Front. Immunol. 10, 333 (2019).","journal-title":"Front. Immunol."},{"key":"1141_CR35","doi-asserted-by":"publisher","first-page":"e32542","DOI":"10.1371\/journal.pone.0032542","volume":"7","author":"S Wan","year":"2012","unstructured":"Wan, S. et al. Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells. PLoS One 7, e32542 (2012).","journal-title":"PLoS One"},{"key":"1141_CR36","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/nri1961","volume":"6","author":"GP Dunn","year":"2006","unstructured":"Dunn, G. P., Koebel, C. M. & Schreiber, R. D. Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol. 6, 836\u2013848 (2006).","journal-title":"Nat. Rev. Immunol."},{"key":"1141_CR37","doi-asserted-by":"publisher","first-page":"e0182786","DOI":"10.1371\/journal.pone.0182786","volume":"12","author":"IA Park","year":"2017","unstructured":"Park, I. A. et al. Expression of the MHC class II in triple-negative breast cancer is associated with tumor-infiltrating lymphocytes and interferon signaling. PLoS One 12, e0182786 (2017).","journal-title":"PLoS One"},{"key":"1141_CR38","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1158\/1078-0432.CCR-18-3200","volume":"25","author":"ML Axelrod","year":"2019","unstructured":"Axelrod, M. L., Cook, R. S., Johnson, D. B. & Balko, J. M. Biological consequences of MHC-II expression by tumor cells in cancer. Clin. Cancer Res. 25, 2392\u20132402 (2019).","journal-title":"Clin. Cancer Res."},{"key":"1141_CR39","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.mrfmmm.2003.07.013","volume":"533","author":"MG Cherian","year":"2003","unstructured":"Cherian, M. G., Jayasurya, A. & Bay, B.-H. Metallothioneins in human tumors and potential roles in carcinogenesis. Mutat. Res. 533, 201\u2013209 (2003).","journal-title":"Mutat. Res."},{"key":"1141_CR40","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1093\/carcin\/23.1.81","volume":"23","author":"R Jin","year":"2002","unstructured":"Jin, R. et al. Metallothionein 2A expression is associated with cell proliferation in breast cancer. Carcinogenesis 23, 81\u201386 (2002).","journal-title":"Carcinogenesis"},{"key":"1141_CR41","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/0960-9776(92)90223-O","volume":"1","author":"H Pereira","year":"1992","unstructured":"Pereira, H. et al. Metallothionein expression in human breast cancer. Breast 1, 159\u2013160 (1992).","journal-title":"Breast"},{"key":"1141_CR42","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.proghi.2008.10.001","volume":"44","author":"M\u00d8 Pedersen","year":"2009","unstructured":"Pedersen, M. \u00d8., Larsen, A., Stoltenberg, M. & Penkowa, M. The role of metallothionein in oncogenesis and cancer prognosis. Prog. Histochem. Cytochem. 44, 29\u201364 (2009).","journal-title":"Prog. Histochem. Cytochem."},{"key":"1141_CR43","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/s41591-019-0750-6","volume":"26","author":"AM Laughney","year":"2020","unstructured":"Laughney, A. M. et al. Regenerative lineages and immune-mediated pruning in lung cancer metastasis. Nat. Med. 26, 259\u2013269 (2020).","journal-title":"Nat. Med."},{"key":"1141_CR44","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.ccell.2020.06.012","volume":"38","author":"ND Marjanovic","year":"2020","unstructured":"Marjanovic, N. D. et al. Emergence of a high-plasticity cell state during lung cancer evolution. Cancer Cell 38, 229\u2013246.e13 (2020).","journal-title":"Cancer Cell"},{"key":"1141_CR45","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/j.cell.2020.07.017","volume":"182","author":"A Maynard","year":"2020","unstructured":"Maynard, A. et al. Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing. Cell 182, 1232\u20131251.e22 (2020).","journal-title":"Cell"},{"key":"1141_CR46","doi-asserted-by":"publisher","first-page":"7400","DOI":"10.1158\/1078-0432.CCR-17-0638","volume":"23","author":"D Hao","year":"2017","unstructured":"Hao, D. et al. Integrated analysis reveals tubal- and ovarian-originated serous ovarian cancer and predicts differential therapeutic responses. Clin. Cancer Res. 23, 7400\u20137411 (2017).","journal-title":"Clin. Cancer Res."},{"key":"1141_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13116-2","volume":"10","author":"S Zhang","year":"2019","unstructured":"Zhang, S. et al. Both fallopian tube and ovarian surface epithelium are cells-of-origin for high-grade serous ovarian carcinoma. Nat. Commun. 10, 5367 (2019).","journal-title":"Nat. Commun."},{"key":"1141_CR48","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1038\/nature15748","volume":"527","author":"KR Fischer","year":"2015","unstructured":"Fischer, K. R. et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature 527, 472\u2013476 (2015).","journal-title":"Nature"},{"key":"1141_CR49","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.devcel.2018.05.027","volume":"45","author":"NM Aiello","year":"2018","unstructured":"Aiello, N. M. et al. EMT subtype influences epithelial plasticity and mode of cell migration. Dev. Cell 45, 681\u2013695.e4 (2018).","journal-title":"Dev. Cell"},{"key":"1141_CR50","doi-asserted-by":"publisher","first-page":"eabi7640","DOI":"10.1126\/sciadv.abi7640","volume":"8","author":"DP Cook","year":"2022","unstructured":"Cook, D. P. & Vanderhyden, B. C. Transcriptional census of epithelial-mesenchymal plasticity in cancer. Sci. Adv. 8, eabi7640 (2022).","journal-title":"Sci. Adv."},{"key":"1141_CR51","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1172\/JCI39104","volume":"119","author":"R Kalluri","year":"2009","unstructured":"Kalluri, R. & Weinberg, R. A. The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119, 1420\u20131428 (2009).","journal-title":"J. Clin. Invest."},{"key":"1141_CR52","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s43018-019-0010-1","volume":"1","author":"A Hayashi","year":"2020","unstructured":"Hayashi, A. et al. A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma. Nat. Cancer 1, 59\u201374 (2020).","journal-title":"Nat. Cancer"},{"key":"1141_CR53","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/nm.2344","volume":"17","author":"EA Collisson","year":"2011","unstructured":"Collisson, E. A. et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat. Med. 17, 500\u2013503 (2011).","journal-title":"Nat. Med."},{"key":"1141_CR54","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1038\/ng.3398","volume":"47","author":"RA Moffitt","year":"2015","unstructured":"Moffitt, R. A. et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat. Genet. 47, 1168\u20131178 (2015).","journal-title":"Nat. Genet."},{"key":"1141_CR55","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1002\/jso.2930050410","volume":"5","author":"SM Baylor","year":"1973","unstructured":"Baylor, S. M. & Berg, J. W. Cross-classification and survival characteristics of 5,000 cases of cancer of the pancreas. J. Surg. Oncol. 5, 335\u2013358 (1973).","journal-title":"J. Surg. Oncol."},{"key":"1141_CR56","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3747\/co.v15i6.265","volume":"15","author":"A Al-Shehri","year":"2008","unstructured":"Al-Shehri, A., Silverman, S. & King, K. M. Squamous cell carcinoma of the pancreas. Curr. Oncol. 15, 293\u2013297 (2008).","journal-title":"Curr. Oncol."},{"key":"1141_CR57","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1126\/science.aaf2403","volume":"353","author":"PL St\u00e5hl","year":"2016","unstructured":"St\u00e5hl, P. L. et al. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 353, 78\u201382 (2016).","journal-title":"Science"},{"key":"1141_CR58","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1038\/nm.2537","volume":"17","author":"SM Weis","year":"2011","unstructured":"Weis, S. M. & Cheresh, D. A. Tumor angiogenesis: molecular pathways and therapeutic targets. Nat. Med. 17, 1359\u20131370 (2011).","journal-title":"Nat. Med."},{"key":"1141_CR59","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s10456-017-9562-9","volume":"20","author":"C Viallard","year":"2017","unstructured":"Viallard, C. & Larriv\u00e9e, B. Tumor angiogenesis and vascular normalization: alternative therapeutic targets. Angiogenesis 20, 409\u2013426 (2017).","journal-title":"Angiogenesis"},{"key":"1141_CR60","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1189\/jlb.0609385","volume":"86","author":"G Solinas","year":"2009","unstructured":"Solinas, G., Germano, G., Mantovani, A. & Allavena, P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J. Leukoc. Biol. 86, 1065\u20131073 (2009).","journal-title":"J. Leukoc. Biol."},{"key":"1141_CR61","doi-asserted-by":"publisher","DOI":"10.1186\/1757-2215-7-19","volume":"7","author":"M Zhang","year":"2014","unstructured":"Zhang, M. et al. A high M1\/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. J. Ovarian Res. 7, 19 (2014).","journal-title":"J. Ovarian Res."},{"key":"1141_CR62","doi-asserted-by":"publisher","DOI":"10.1038\/srep14273","volume":"5","author":"A Yuan","year":"2015","unstructured":"Yuan, A. et al. Opposite effects of M1 and M2 macrophage subtypes on lung cancer progression. Sci. Rep. 5, 14273 (2015).","journal-title":"Sci. Rep."},{"key":"1141_CR63","doi-asserted-by":"publisher","first-page":"3802","DOI":"10.1038\/s41596-021-00556-8","volume":"16","author":"S Black","year":"2021","unstructured":"Black, S. et al. CODEX multiplexed tissue imaging with DNA-conjugated antibodies. Nat. Protoc. 16, 3802\u20133835 (2021).","journal-title":"Nat. Protoc."},{"key":"1141_CR64","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1084\/jem.20101158","volume":"208","author":"MS Diamond","year":"2011","unstructured":"Diamond, M. S. et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J. Exp. Med. 208, 1989\u20132003 (2011).","journal-title":"J. Exp. Med."},{"key":"1141_CR65","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.immuni.2014.10.019","volume":"41","author":"L Deng","year":"2014","unstructured":"Deng, L. et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41, 843\u2013852 (2014).","journal-title":"Immunity"},{"key":"1141_CR66","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.it.2017.07.013","volume":"39","author":"KW Ng","year":"2018","unstructured":"Ng, K. W., Marshall, E. A., Bell, J. C. & Lam, W. L. cGAS-STING and cancer: dichotomous roles in tumor immunity and development. Trends Immunol. 39, 44\u201354 (2018).","journal-title":"Trends Immunol."},{"key":"1141_CR67","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14290-4","volume":"11","author":"JB Williams","year":"2020","unstructured":"Williams, J. B. et al. Tumor heterogeneity and clonal cooperation influence the immune selection of IFN-\u03b3-signaling mutant cancer cells. Nat. Commun. 11, 602 (2020).","journal-title":"Nat. Commun."},{"key":"1141_CR68","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1038\/s41588-020-00726-6","volume":"52","author":"GS Kinker","year":"2020","unstructured":"Kinker, G. S. et al. Pan-cancer single cell RNA-seq uncovers recurring programs of cellular heterogeneity. Nat. Genet. 52, 1208\u20131218 (2020).","journal-title":"Nat. Genet."},{"key":"1141_CR69","unstructured":"Weinberg, R. A. The Biology of Cancer (Garland Publishing, 2007)."},{"key":"1141_CR70","doi-asserted-by":"publisher","first-page":"6118","DOI":"10.1158\/1078-0432.CCR-11-0482","volume":"17","author":"MR Zaidi","year":"2011","unstructured":"Zaidi, M. R. & Merlino, G. The two faces of interferon-\u03b3 in cancer. Clin. Cancer Res. 17, 6118\u20136124 (2011).","journal-title":"Clin. Cancer Res."},{"key":"1141_CR71","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/ng.3214","volume":"47","author":"A Sottoriva","year":"2015","unstructured":"Sottoriva, A. et al. A Big Bang model of human colorectal tumor growth. Nat. Genet. 47, 209\u2013216 (2015).","journal-title":"Nat. Genet."},{"key":"1141_CR72","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":"1141_CR73","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":"1141_CR74","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/s41568-018-0083-7","volume":"19","author":"M Archetti","year":"2019","unstructured":"Archetti, M. & Pienta, K. J. Cooperation among cancer cells: applying game theory to cancer. Nat. Rev. Cancer 19, 110\u2013117 (2019).","journal-title":"Nat. Rev. Cancer"},{"key":"1141_CR75","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/j.cell.2015.04.044","volume":"161","author":"AM Klein","year":"2015","unstructured":"Klein, A. M. et al. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161, 1187\u20131201 (2015).","journal-title":"Cell"},{"key":"1141_CR76","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.cels.2016.08.011","volume":"3","author":"M Baron","year":"2016","unstructured":"Baron, M. et al. A single-cell transcriptomic map of the human and mouse pancreas reveals inter- and intra-cell population structure. Cell Syst. 3, 346\u2013360.e4 (2016).","journal-title":"Cell Syst."},{"key":"1141_CR77","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1","volume":"20","author":"C Hafemeister","year":"2019","unstructured":"Hafemeister, C. & Satija, R. Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. Genome Biol. 20, 296 (2019).","journal-title":"Genome Biol."},{"key":"1141_CR78","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888\u20131902.e21 (2019).","journal-title":"Cell"},{"key":"1141_CR79","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26343-3","volume":"12","author":"W Pu","year":"2021","unstructured":"Pu, W. et al. Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma. Nat. Commun. 12, 6058 (2021).","journal-title":"Nat. Commun."},{"key":"1141_CR80","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-632","volume":"14","author":"NA Mabbott","year":"2013","unstructured":"Mabbott, N. A., Baillie, J. K., Brown, H., Freeman, T. C. & Hume, D. A. An expression atlas of human primary cells: inference of gene function from coexpression networks. BMC Genomics 14, 632 (2013).","journal-title":"BMC Genomics"},{"key":"1141_CR81","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/modpathol.3800612","volume":"19","author":"MT Galgano","year":"2006","unstructured":"Galgano, M. T., Hampton, G. M. & Frierson, H. F. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod. Pathol. 19, 847\u2013853 (2006).","journal-title":"Mod. Pathol."},{"key":"1141_CR82","first-page":"1391","volume":"5","author":"L Chen","year":"1990","unstructured":"Chen, L., O\u2019Bryan, J. P., Smith, H. S. & Liu, E. Overexpression of matrix Gla protein mRNA in malignant human breast cells: isolation by differential cDNA hybridization. Oncogene 5, 1391\u20131395 (1990).","journal-title":"Oncogene"},{"key":"1141_CR83","doi-asserted-by":"publisher","first-page":"2820","DOI":"10.1074\/mcp.M112.023507","volume":"12","author":"H Kosanam","year":"2013","unstructured":"Kosanam, H. et al. Laminin, gamma 2 (LAMC2): a promising new putative pancreatic cancer biomarker identified by proteomic analysis of pancreatic adenocarcinoma tissues. Mol. Cell. Proteom. 12, 2820\u20132832 (2013).","journal-title":"Mol. Cell. Proteom."},{"key":"1141_CR84","doi-asserted-by":"publisher","first-page":"490","DOI":"10.3892\/ijo.2015.3022","volume":"47","author":"B Zheng","year":"2015","unstructured":"Zheng, B. et al. TM4SF1 as a prognostic marker of pancreatic ductal adenocarcinoma is involved in migration and invasion of cancer cells. Int. J. Oncol. 47, 490\u2013498 (2015).","journal-title":"Int. J. Oncol."},{"key":"1141_CR85","first-page":"250","volume":"143","author":"S Jothy","year":"1993","unstructured":"Jothy, S., Yuan, S. Y. & Shirota, K. Transcription of carcinoembryonic antigen in normal colon and colon carcinoma. In situ hybridization study and implication for a new in vivo functional model. Am. J. Pathol. 143, 250\u2013257 (1993).","journal-title":"Am. J. Pathol."},{"key":"1141_CR86","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1007\/s00432-010-0825-8","volume":"136","author":"X Jing","year":"2010","unstructured":"Jing, X., Piao, Y.-F., Liu, Y. & Gao, P.-J. Beta2-GPI: a novel factor in the development of hepatocellular carcinoma. J. Cancer Res. Clin. Oncol. 136, 1671\u20131680 (2010).","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"1141_CR87","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/sj.bjc.6604486","volume":"99","author":"KA Landers","year":"2008","unstructured":"Landers, K. A. et al. Identification of claudin-4 as a marker highly overexpressed in both primary and metastatic prostate cancer. Br. J. Cancer 99, 491\u2013501 (2008).","journal-title":"Br. J. Cancer"},{"key":"1141_CR88","first-page":"2827","volume":"57","author":"SY Liao","year":"1997","unstructured":"Liao, S. Y., Aurelio, O. N., Jan, K., Zavada, J. & Stanbridge, E. J. Identification of the MN\/CA9 protein as a reliable diagnostic biomarker of clear cell carcinoma of the kidney. Cancer Res. 57, 2827\u20132831 (1997).","journal-title":"Cancer Res."},{"key":"1141_CR89","first-page":"8624","volume":"61","author":"SV Allander","year":"2001","unstructured":"Allander, S. V. et al. Gastrointestinal stromal tumors with KIT mutations exhibit a remarkably homogeneous gene expression profile. Cancer Res. 61, 8624\u20138628 (2001).","journal-title":"Cancer Res."},{"key":"1141_CR90","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S0002-9440(10)63279-8","volume":"165","author":"RB West","year":"2004","unstructured":"West, R. B. et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am. J. Pathol. 165, 107\u2013113 (2004).","journal-title":"Am. J. Pathol."},{"key":"1141_CR91","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1186\/1471-2105-11-367","volume":"11","author":"R Gaujoux","year":"2010","unstructured":"Gaujoux, R. & Seoighe, C. A flexible R package for nonnegative matrix factorization. BMC Bioinf. 11, 367 (2010).","journal-title":"BMC Bioinf."},{"key":"1141_CR92","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/1471-2105-7-78","volume":"7","author":"P Carmona-Saez","year":"2006","unstructured":"Carmona-Saez, P., Pascual-Marqui, R. D., Tirado, F., Carazo, J. M. & Pascual-Montano, A. Biclustering of gene expression data by non-smooth non-negative matrix factorization. BMC Bioinf. 7, 78 (2006).","journal-title":"BMC Bioinf."},{"key":"1141_CR93","unstructured":"Csardi, G., Nepusz, T. The igraph software package for complex network research. InterJournal 1695 (2006)."},{"key":"1141_CR94","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","volume":"14","author":"S Aibar","year":"2017","unstructured":"Aibar, S. et al. SCENIC: single-cell regulatory network inference and clustering. Nat. Methods 14, 1083\u20131086 (2017).","journal-title":"Nat. Methods"},{"key":"1141_CR95","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545\u201315550 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1141_CR96","doi-asserted-by":"publisher","first-page":"baz046","DOI":"10.1093\/database\/baz046","volume":"2019","author":"O Franz\u00e9n","year":"2019","unstructured":"Franz\u00e9n, O., Gan, L.-M. & Bj\u00f6rkegren, J. L. M. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database (Oxford) 2019, baz046 (2019).","journal-title":"Database (Oxford)"},{"key":"1141_CR97","unstructured":"Mullen, K. M., van Stokkum, I. H. M. & Mullen, M. K. nnls: The Lawson-Hanson algorithm for non-negative least squares (NNLS). R package version 1.4 https:\/\/CRAN.R-project.org\/package=nnls (2015)."},{"key":"1141_CR98","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1093\/bioinformatics\/bti525","volume":"21","author":"S Durinck","year":"2005","unstructured":"Durinck, S. et al. BioMart and Bioconductor: a powerful link between biological databases and microarray data analysis. Bioinformatics 21, 3439\u20133440 (2005).","journal-title":"Bioinformatics"},{"key":"1141_CR99","doi-asserted-by":"publisher","unstructured":"Barkley, D. Code for the analyses described in Barkley et al. Nature Genetics. Zenodo https:\/\/doi.org\/10.5281\/zenodo.6611786 (2022).","DOI":"10.5281\/zenodo.6611786"}],"container-title":["Nature Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41588-022-01141-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41588-022-01141-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41588-022-01141-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T12:35:00Z","timestamp":1662640500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41588-022-01141-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":99,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["1141"],"URL":"https:\/\/doi.org\/10.1038\/s41588-022-01141-9","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742269703.793594913","asserted-by":"object"}]},"ISSN":["1061-4036","1546-1718"],"issn-type":[{"value":"1061-4036","type":"print"},{"value":"1546-1718","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8]]},"assertion":[{"value":"20 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}