{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T02:57:49Z","timestamp":1793761069692,"version":"4.6.1"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF21OC0068988"],"award-info":[{"award-number":["NNF21OC0068988"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF21OC0072031"],"award-info":[{"award-number":["NNF21OC0072031"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R396-2022-350"],"award-info":[{"award-number":["R396-2022-350"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A comprehensive investigation of ovarian cancer (OC) progression at the single-cell level is crucial for enhancing our understanding of the disease, as well as for the development of better diagnoses and treatments. Here, over half a million single-cell transcriptome data were collected from 84 OC patients across all clinical stages. Through integrative analysis, we identified heterogeneous epithelial-immune-stromal cellular compartments and their interactions in the OC microenvironment. The epithelial cells displayed clinical subtype features with functional variance. A significant increase in distinct T cell subtypes was identified including Tregs and CD8+ exhausted T cells from stage IC2. Additionally, we discovered antigen-presenting cancer-associated fibroblasts (CAFs), with myofibroblastic CAFs (myCAFs) exhibiting enriched extracellular matrix (ECM) functionality linked to tumor progression at stage IC2. Furthermore, the NECTIN2-TIGIT ligand-receptor pair was identified to mediate T cells communicating with epithelial, fibroblast, endothelial, and other cell types. Knock-out of\n                    <jats:italic>NECTIN2<\/jats:italic>\n                    using CRISPR\/Cas9 inhibited ovarian cancer cell (SKOV3) proliferation, and increased T cell proliferation when co-cultured. These findings shed light on the cellular compartments and functional aspects of OC, providing insights into the molecular mechanisms underlying stage IC2 and potential therapeutic strategies for OC.\n                  <\/jats:p>","DOI":"10.1038\/s42003-024-05826-1","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T02:02:15Z","timestamp":1706234535000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer"],"prefix":"10.1038","volume":"7","author":[{"given":"Chaochao","family":"Chai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Langchao","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanna S.","family":"Mikkelsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wandong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-0297","authenticated-orcid":false,"given":"Rasmus O.","family":"Bak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8778-9988","authenticated-orcid":false,"given":"Hanbo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7546-4948","authenticated-orcid":false,"given":"Lin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1751-7108","authenticated-orcid":false,"given":"Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7759","authenticated-orcid":false,"given":"Yonglun","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,26]]},"reference":[{"key":"5826_CR1","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3322\/caac.21559","volume":"69","author":"S Lheureux","year":"2019","unstructured":"Lheureux, S., Braunstein, M. & Oza, A. M. Epithelial ovarian cancer: evolution of management in the era of precision medicine. Ca. Cancer J. Clin. 69, 280\u2013304 (2019).","journal-title":"Ca. Cancer J. Clin."},{"key":"5826_CR2","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1097\/CM9.0000000000002108","volume":"135","author":"C Xia","year":"2022","unstructured":"Xia, C. et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin. Med. J. 135, 584\u2013590 (2022).","journal-title":"Chin. Med. J."},{"key":"5826_CR3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel, R. L., Miller, K. D., Wagle, N. S. & Jemal, A. Cancer statistics, 2023. Ca. Cancer J. Clin. 73, 17\u201348 (2023).","journal-title":"Ca. Cancer J. Clin."},{"key":"5826_CR4","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1016\/S0140-6736(09)61338-6","volume":"374","author":"BT Hennessy","year":"2009","unstructured":"Hennessy, B. T., Coleman, R. L. & Markman, M. Ovarian cancer. Lancet 374, 1371\u20131382 (2009).","journal-title":"Lancet"},{"key":"5826_CR5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.semcancer.2017.04.009","volume":"44","author":"PB Ottevanger","year":"2017","unstructured":"Ottevanger, P. B. Ovarian cancer stem cells more questions than answers. Semin. Cancer Biol. 44, 67\u201371 (2017).","journal-title":"Semin. Cancer Biol."},{"key":"5826_CR6","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/S0140-6736(15)01224-6","volume":"387","author":"IJ Jacobs","year":"2016","unstructured":"Jacobs, I. J. et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet 387, 945\u2013956 (2016).","journal-title":"Lancet"},{"key":"5826_CR7","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ygyno.2008.08.031","volume":"112","author":"RG Moore","year":"2009","unstructured":"Moore, R. G. et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol. Oncol. 112, 40\u201346 (2009).","journal-title":"Gynecol. Oncol."},{"key":"5826_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-022-02651-9","volume":"23","author":"Y Shi","year":"2022","unstructured":"Shi, Y. et al. Decoding the multicellular ecosystem of vena caval tumor thrombus in clear cell renal cell carcinoma by single-cell RNA sequencing. Genome Biol. 23, 87 (2022).","journal-title":"Genome Biol."},{"key":"5826_CR9","doi-asserted-by":"publisher","first-page":"eabm1831","DOI":"10.1126\/sciadv.abm1831","volume":"8","author":"K Zhang","year":"2022","unstructured":"Zhang, K. et al. Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer. Sci. Adv. 8, eabm1831 (2022).","journal-title":"Sci. Adv."},{"key":"5826_CR10","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/s43018-022-00411-z","volume":"3","author":"D Lavie","year":"2022","unstructured":"Lavie, D., Ben-Shmuel, A., Erez, N. & Scherz-Shouval, R. Cancer-associated fibroblasts in the single-cell era. Nat. Cancer 3, 793\u2013807 (2022).","journal-title":"Nat. Cancer"},{"key":"5826_CR11","doi-asserted-by":"publisher","first-page":"3590","DOI":"10.1158\/1078-0432.CCR-22-0296","volume":"28","author":"J Xu","year":"2022","unstructured":"Xu, J. et al. Single-cell RNA sequencing reveals the tissue architecture in human high-grade serous ovarian cancer. Clin. Cancer Res. 28, 3590\u20133602 (2022).","journal-title":"Clin. Cancer Res."},{"key":"5826_CR12","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1097\/01.pas.0000213335.40358.47","volume":"31","author":"DW Kindelberger","year":"2007","unstructured":"Kindelberger, D. W. et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am. J. Surg. Pathol. 31, 161\u2013169 (2007).","journal-title":"Am. J. Surg. Pathol."},{"key":"5826_CR13","doi-asserted-by":"publisher","first-page":"4924","DOI":"10.1016\/j.molcel.2021.10.013","volume":"81","author":"MJ Regner","year":"2021","unstructured":"Regner, M. J. et al. A multi-omic single-cell landscape of human gynecologic malignancies. Mol. Cell 81, 4924\u20134941.e10 (2021).","journal-title":"Mol. Cell"},{"key":"5826_CR14","doi-asserted-by":"publisher","first-page":"3903","DOI":"10.1158\/0008-5472.CAN-21-3819","volume":"82","author":"Y Wang","year":"2022","unstructured":"Wang, Y. et al. Single-cell dissection of the multiomic landscape of high-grade serous ovarian cancer. Cancer Res. 82, 3903\u20133916 (2022).","journal-title":"Cancer Res."},{"key":"5826_CR15","doi-asserted-by":"publisher","first-page":"100856","DOI":"10.1016\/j.xcrm.2022.100856","volume":"3","author":"B Yang","year":"2022","unstructured":"Yang, B. et al. Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis. Cell Rep. Med. 3, 100856 (2022).","journal-title":"Cell Rep. Med."},{"key":"5826_CR16","doi-asserted-by":"publisher","first-page":"4335","DOI":"10.1158\/0008-5472.CAN-20-0521","volume":"80","author":"L Geistlinger","year":"2020","unstructured":"Geistlinger, L. et al. Multiomic analysis of subtype evolution and heterogeneity in high-grade serous ovarian carcinoma. Cancer Res. 80, 4335\u20134345 (2020).","journal-title":"Cancer Res."},{"key":"5826_CR17","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.3390\/cancers14112637","volume":"14","author":"M Zhang","year":"2022","unstructured":"Zhang, M., Chen, Z., Wang, Y., Zhao, H. & Du, Y. The role of cancer-associated fibroblasts in ovarian cancer. Cancers 14, 2637 (2022).","journal-title":"Cancers"},{"key":"5826_CR18","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":"5826_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ygyno.2018.09.005","volume":"151","author":"W Wang","year":"2018","unstructured":"Wang, W., Zou, W. & Liu, J. R. Tumor-infiltrating T cells in epithelial ovarian cancer: predictors of prognosis and biological basis of immunotherapy. Gynecol. Oncol. 151, 1\u20133 (2018).","journal-title":"Gynecol. Oncol."},{"key":"5826_CR20","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.ccell.2022.03.008","volume":"40","author":"CM Anadon","year":"2022","unstructured":"Anadon, C. M. et al. Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells. Cancer Cell 40, 545\u2013557.e13 (2022).","journal-title":"Cancer Cell"},{"key":"5826_CR21","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/s41577-019-0221-9","volume":"19","author":"CU Blank","year":"2019","unstructured":"Blank, C. U. et al. Defining \u2018T cell exhaustion. Nat. Rev. Immunol. 19, 665\u2013674 (2019).","journal-title":"Nat. Rev. Immunol."},{"key":"5826_CR22","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/s41571-022-00689-z","volume":"19","author":"A Chow","year":"2022","unstructured":"Chow, A., Perica, K., Klebanoff, C. A. & Wolchok, J. D. Clinical implications of T cell exhaustion for cancer immunotherapy. Nat. Rev. Clin. Oncol. 19, 775\u2013790 (2022).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"5826_CR23","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1111\/j.1365-2567.2010.03255.x","volume":"129","author":"JS Yi","year":"2010","unstructured":"Yi, J. S., Cox, M. A. & Zajac, A. J. T-cell exhaustion: characteristics, causes and conversion. Immunology 129, 474\u2013481 (2010).","journal-title":"Immunology"},{"key":"5826_CR24","doi-asserted-by":"publisher","first-page":"1192777","DOI":"10.3389\/fphar.2023.1192777","volume":"14","author":"K Yuan","year":"2023","unstructured":"Yuan, K. et al. A novel T-cell exhaustion-related feature can accurately predict the prognosis of OC patients. Front. Pharmacol. 14, 1192777 (2023).","journal-title":"Front. Pharmacol."},{"key":"5826_CR25","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289\u20131296 (2019).","journal-title":"Nat. Methods"},{"key":"5826_CR26","doi-asserted-by":"publisher","first-page":"4089","DOI":"10.1158\/1078-0432.CCR-20-4394","volume":"27","author":"CM Laumont","year":"2021","unstructured":"Laumont, C. M. et al. Single-cell profiles and prognostic impact of tumor-infiltrating lymphocytes coexpressing CD39, CD103, and PD-1 in Ovarian Cancer. Clin. Cancer Res. 27, 4089\u20134100 (2021).","journal-title":"Clin. Cancer Res."},{"key":"5826_CR27","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/s41591-020-0844-1","volume":"26","author":"M Slyper","year":"2020","unstructured":"Slyper, M. et al. A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors. Nat. Med. 26, 792\u2013802 (2020).","journal-title":"Nat. Med."},{"key":"5826_CR28","doi-asserted-by":"publisher","first-page":"e43803","DOI":"10.7554\/eLife.43803","volume":"8","author":"D Kotliar","year":"2019","unstructured":"Kotliar, D. et al. Identifying gene expression programs of cell-type identity and cellular activity with single-cell RNA-Seq. eLife 8, e43803 (2019).","journal-title":"eLife"},{"key":"5826_CR29","doi-asserted-by":"publisher","first-page":"D900","DOI":"10.1093\/nar\/gky939","volume":"47","author":"H Yuan","year":"2019","unstructured":"Yuan, H. et al. CancerSEA: a cancer single-cell state atlas. Nucleic Acids Res. 47, D900\u2013D908 (2019).","journal-title":"Nucleic Acids Res."},{"key":"5826_CR30","doi-asserted-by":"publisher","first-page":"5","DOI":"10.6026\/97320630002005","volume":"2","author":"L Kumar","year":"2007","unstructured":"Kumar, L., Futschik, E. & Mfuzz, M. A software package for soft clustering of microarray data. Bioinformation 2, 5\u20137 (2007).","journal-title":"Bioinformation"},{"key":"5826_CR31","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 major histocompatibility Class-II expression by tumor cells in cancer. Clin. Cancer Res. 25, 2392\u20132402 (2019).","journal-title":"Clin. Cancer Res."},{"key":"5826_CR32","doi-asserted-by":"publisher","first-page":"7667","DOI":"10.1158\/1078-0432.CCR-08-0479","volume":"14","author":"MJ Callahan","year":"2008","unstructured":"Callahan, M. J. et al. Increased HLA-DMB Expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer. Clin. Cancer Res. 14, 7667\u20137673 (2008).","journal-title":"Clin. Cancer Res."},{"key":"5826_CR33","doi-asserted-by":"publisher","first-page":"5173","DOI":"10.4049\/jimmunol.1002050","volume":"186","author":"P Hemon","year":"2011","unstructured":"Hemon, P. et al. MHC Class II engagement by Its Ligand LAG-3 (CD223) contributes to melanoma resistance to apoptosis. J. Immunol. 186, 5173\u20135183 (2011).","journal-title":"J. Immunol."},{"key":"5826_CR34","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1146\/annurev-immunol-032414-112049","volume":"34","author":"SH Baumeister","year":"2016","unstructured":"Baumeister, S. H., Freeman, G. J., Dranoff, G. & Sharpe, A. H. Coinhibitory pathways in immunotherapy for cancer. Annu. Rev. Immunol. 34, 539\u2013573 (2016).","journal-title":"Annu. Rev. Immunol."},{"key":"5826_CR35","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nm863","volume":"9","author":"TJ Curiel","year":"2003","unstructured":"Curiel, T. J. et al. Blockade of B7-H1 improves myeloid dendritic cell\u2013mediated antitumor immunity. Nat. Med. 9, 562\u2013567 (2003).","journal-title":"Nat. Med."},{"key":"5826_CR36","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nrc2644","volume":"9","author":"RC Bast","year":"2009","unstructured":"Bast, R. C., Hennessy, B. & Mills, G. B. The biology of ovarian cancer: new opportunities for translation. Nat. Rev. Cancer 9, 415 (2009).","journal-title":"Nat. Rev. Cancer"},{"key":"5826_CR37","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/s43018-020-0082-y","volume":"1","author":"G Friedman","year":"2020","unstructured":"Friedman, G. et al. Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4+ and PDPN+ CAFs to clinical outcome. Nat. Cancer 1, 692\u2013708 (2020).","journal-title":"Nat. Cancer"},{"key":"5826_CR38","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1158\/2159-8290.CD-19-0094","volume":"9","author":"E Elyada","year":"2019","unstructured":"Elyada, E. et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts.Cancer Discov. 9, 1102\u20131123 (2019).","journal-title":"Cancer Discov."},{"key":"5826_CR39","doi-asserted-by":"publisher","first-page":"e20210815","DOI":"10.1084\/jem.20210815","volume":"219","author":"D Kerdidani","year":"2022","unstructured":"Kerdidani, D. et al. Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts. J. Exp. Med. 219, e20210815 (2022).","journal-title":"J. Exp. Med."},{"key":"5826_CR40","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":"5826_CR41","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1158\/0008-5472.CAN-18-2616","volume":"79","author":"S Natarajan","year":"2019","unstructured":"Natarajan, S. et al. Collagen remodeling in the hypoxic tumor-mesothelial niche promotes ovarian cancer metastasis. Cancer Res. 79, 2271\u20132284 (2019).","journal-title":"Cancer Res."},{"key":"5826_CR42","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/s41374-021-00546-0","volume":"101","author":"Y Lyu","year":"2021","unstructured":"Lyu, Y. & Feng, C. Collagen synthesis and gap junctions: the highway for metastasis of ovarian cancer. Lab. Investig. 101, 540\u2013542 (2021).","journal-title":"Lab. Investig."},{"key":"5826_CR43","first-page":"913","volume":"18","author":"Y Yoshida","year":"2001","unstructured":"Yoshida, Y. et al. Role of laminin in ovarian cancer tumor growth and metastasis via regulation of Mdm2 and Bcl-2 expression. Int. J. Oncol. 18, 913\u2013921 (2001).","journal-title":"Int. J. Oncol."},{"key":"5826_CR44","doi-asserted-by":"publisher","first-page":"48","DOI":"10.4161\/cam.22826","volume":"7","author":"M Aumailley","year":"2013","unstructured":"Aumailley, M. The laminin family. Cell Adhes. Migr. 7, 48\u201355 (2013).","journal-title":"Cell Adhes. Migr."},{"key":"5826_CR45","doi-asserted-by":"publisher","first-page":"508","DOI":"10.4161\/cib.3.6.13495","volume":"3","author":"BJ Baaten","year":"2010","unstructured":"Baaten, B. J., Li, C.-R. & Bradley, L. M. Multifaceted regulation of T cells by CD44. Commun. Integr. Biol. 3, 508\u2013512 (2010).","journal-title":"Commun. Integr. Biol."},{"key":"5826_CR46","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3390\/biom13010023","volume":"13","author":"CB Brandt","year":"2022","unstructured":"Brandt, C. B. et al. HIF1A Knockout by Biallelic and selection-free CRISPR gene editing in human primary endothelial cells with ribonucleoprotein complexes. Biomolecules 13, 23 (2022).","journal-title":"Biomolecules"},{"key":"5826_CR47","doi-asserted-by":"publisher","first-page":"e21692","DOI":"10.1096\/fj.202002558RR","volume":"35","author":"F Graf","year":"2021","unstructured":"Graf, F., Horn, P., Ho, A. D., Boutros, M. & Maercker, C. The extracellular matrix proteins type I collagen, type III collagen, fibronectin, and laminin 421 stimulate migration of cancer cells. FASEB J. 35, e21692 (2021).","journal-title":"FASEB J."},{"key":"5826_CR48","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/s41577-020-0296-3","volume":"20","author":"LE Lucca","year":"2020","unstructured":"Lucca, L. E. & Dominguez-Villar, M. Modulation of regulatory T cell function and stability by co-inhibitory receptors. Nat. Rev. Immunol. 20, 680\u2013693 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"5826_CR49","doi-asserted-by":"publisher","first-page":"3584","DOI":"10.1002\/cam4.2976","volume":"9","author":"F Chen","year":"2020","unstructured":"Chen, F., Xu, Y., Chen, Y. & Shan, S. TIGIT enhances CD4+ regulatory T-cell response and mediates immune suppression in a murine ovarian cancer model. Cancer Med. 9, 3584\u20133591 (2020).","journal-title":"Cancer Med."},{"key":"5826_CR50","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.ccell.2014.10.018","volume":"26","author":"RJ Johnston","year":"2014","unstructured":"Johnston, R. J. et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. Cancer Cell 26, 923\u2013937 (2014).","journal-title":"Cancer Cell"},{"key":"5826_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-12-60","volume":"12","author":"T Oshima","year":"2013","unstructured":"Oshima, T. et al. Nectin-2 is a potential target for antibody therapy of breast and ovarian cancers. Mol. Cancer 12, 60 (2013).","journal-title":"Mol. Cancer"},{"key":"5826_CR52","doi-asserted-by":"publisher","first-page":"12358","DOI":"10.3390\/ijms232012358","volume":"23","author":"YH Sim","year":"2022","unstructured":"Sim, Y. H., Um, Y. J., Park, J.-Y., Seo, M.-D. & Park, S. G. A novel antibody-drug conjugate targeting Nectin-2 suppresses ovarian cancer progression in mouse xenograft models. Int. J. Mol. Sci. 23, 12358 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"5826_CR53","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573\u20133587.e29 (2021).","journal-title":"Cell"},{"key":"5826_CR54","first-page":"100141","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu, T. et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innov. Camb. Mass 2, 100141 (2021).","journal-title":"Innov. Camb. Mass"},{"key":"5826_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","volume":"14","author":"S H\u00e4nzelmann","year":"2013","unstructured":"H\u00e4nzelmann, S., Castelo, R. & Guinney, J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinforma. 14, 7 (2013).","journal-title":"BMC Bioinforma."},{"key":"5826_CR56","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/nmeth.4402","volume":"14","author":"X Qiu","year":"2017","unstructured":"Qiu, X. et al. Reversed graph embedding resolves complex single-cell trajectories. Nat. Methods 14, 979\u2013982 (2017).","journal-title":"Nat. Methods"},{"key":"5826_CR57","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15599","volume":"8","author":"AE Teschendorff","year":"2017","unstructured":"Teschendorff, A. E. & Enver, T. Single-cell entropy for accurate estimation of differentiation potency from a cell\u2019s transcriptome. Nat. Commun. 8, 15599 (2017).","journal-title":"Nat. Commun."},{"key":"5826_CR58","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9","volume":"12","author":"S Jin","year":"2021","unstructured":"Jin, S. et al. Inference and analysis of cell-cell communication using CellChat. Nat. Commun. 12, 1088 (2021).","journal-title":"Nat. Commun."},{"key":"5826_CR59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23576-0","volume":"12","author":"X Xiang","year":"2021","unstructured":"Xiang, X. et al. Enhancing CRISPR-Cas9 gRNA efficiency prediction by data integration and deep learning. Nat. Commun. 12, 3238 (2021).","journal-title":"Nat. Commun."},{"key":"5826_CR60","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.devcel.2022.02.017","volume":"57","author":"ND Ulrich","year":"2022","unstructured":"Ulrich, N. D. et al. Cellular heterogeneity of human fallopian tubes in normal and hydrosalpinx disease states identified using scRNA-seq. Dev. Cell 57, 914\u2013929.e7 (2022).","journal-title":"Dev. Cell"},{"key":"5826_CR61","doi-asserted-by":"publisher","first-page":"108978","DOI":"10.1016\/j.celrep.2021.108978","volume":"35","author":"HQ Dinh","year":"2021","unstructured":"Dinh, H. Q. et al. Single-cell transcriptomics identifies gene expression networks driving differentiation and tumorigenesis in the human fallopian tube. Cell Rep. 35, 108978 (2021).","journal-title":"Cell Rep."},{"key":"5826_CR62","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/s41422-020-0355-0","volume":"30","author":"J Qian","year":"2020","unstructured":"Qian, J. et al. A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling. Cell Res. 30, 745\u2013762 (2020).","journal-title":"Cell Res."},{"key":"5826_CR63","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-021-00922-x","volume":"13","author":"S Olbrecht","year":"2021","unstructured":"Olbrecht, S. et al. High-grade serous tubo-ovarian cancer refined with single-cell RNA sequencing: specific cell subtypes influence survival and determine molecular subtype classification. Genome Med. 13, 111 (2021).","journal-title":"Genome Med."},{"key":"5826_CR64","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1158\/0008-5472.CAN-20-1674","volume":"81","author":"C Wan","year":"2021","unstructured":"Wan, C. et al. Enhanced efficacy of simultaneous PD-1 and PD-L1 immune checkpoint blockade in high-grade serous ovarian cancer. Cancer Res. 81, 158\u2013173 (2021).","journal-title":"Cancer Res."},{"key":"5826_CR65","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/s41388-021-02139-z","volume":"41","author":"T Kan","year":"2022","unstructured":"Kan, T. et al. Single-cell RNA-seq recognized the initiator of epithelial ovarian cancer recurrence. Oncogene 41, 895\u2013906 (2022).","journal-title":"Oncogene"},{"key":"5826_CR66","doi-asserted-by":"publisher","first-page":"e1009290","DOI":"10.1371\/journal.pcbi.1009290","volume":"17","author":"AA Hippen","year":"2021","unstructured":"Hippen, A. A. et al. miQC: an adaptive probabilistic framework for quality control of single-cell RNA-sequencing data. PLoS Comput. Biol. 17, e1009290 (2021).","journal-title":"PLoS Comput. Biol."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05826-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05826-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05826-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T03:06:44Z","timestamp":1706238404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05826-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,26]]},"references-count":66,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["5826"],"URL":"https:\/\/doi.org\/10.1038\/s42003-024-05826-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3024248\/v1","asserted-by":"object"}]},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,26]]},"assertion":[{"value":"5 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2024","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"}},{"value":"The inclusion of collaborators and authors to all the research and analytic work in this study is conducted according to the Global Code of Conduct.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"131"}}