{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:55:20Z","timestamp":1785426920172,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,30]]},"group-title":"Cancer Biology","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA182413"],"award-info":[{"award-number":["CA182413"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA260115"],"award-info":[{"award-number":["CA260115"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA248524"],"award-info":[{"award-number":["CA248524"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U54AG079779"],"award-info":[{"award-number":["U54AG079779"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P20 GM130423"],"award-info":[{"award-number":["P20 GM130423"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30 CA168524"],"award-info":[{"award-number":["P30 CA168524"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ovarian Cancer Research Fund","award":["327516"],"award-info":[{"award-number":["327516"]}]},{"name":"the Chan Zuckerberg Initiative Single-Cell Biology Data Insights","award":["DAF2023-323354"],"award-info":[{"award-number":["DAF2023-323354"]}]},{"id":[{"id":"https:\/\/ror.org\/04vdd6t03","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023581","name":"NSF Graduate Research Fellowship Program","doi-asserted-by":"crossref","award":["DGE-2139899"],"award-info":[{"award-number":["DGE-2139899"]}],"id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  High-grade serous carcinoma (HGSC), the most lethal form of ovarian cancer, preferentially originates in the tubal epithelium (TE) of the distal uterine tube (also known as Fallopian tube or oviduct). Mouse models are widely used to study how HGSC initiates in humans; however, the extent to which mouse and human uterine tubes are comparable remains unclear. Here, we conduct cross-species single-cell transcriptomic comparative analyses and organoid assay validations to reveal conserved differentiation trajectories from bipotent progenitors to secretory or ciliated cell fates. Regional analyses of both datasets reveal enriched injury repair features in the distal human TE, where mice lack such a trend. Experimentally inducing mechanical injury to the mouse TE yields significant expansion of pre-ciliated cells compared to uninjured counterparts. Furthermore, inactivation of\n                  <jats:italic>Trp53<\/jats:italic>\n                  and\n                  <jats:italic>Rb1,<\/jats:italic>\n                  whose pathways are commonly altered in HGSC, in regenerating pre-ciliated cells leads to rapid neoplastic transformation, implicating post-traumatic repair as a permissive window for malignant transformation. Together, our findings establish a comparative atlas of cell states between mice and humans, show that injury-associated regeneration may contribute to the known vulnerability of the fimbrial region, and raise potential concerns regarding procedures or conditions that mechanically perturb the tubal epithelium.\n                <\/jats:p>","DOI":"10.64898\/2026.03.26.714557","type":"posted-content","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:40:20Z","timestamp":1774896020000},"source":"Crossref","is-referenced-by-count":0,"title":["Comparative single-cell atlases reveal injury-driven tubal epithelial regeneration as a window for ovarian carcinoma initiation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-6482","authenticated-orcid":false,"given":"Coulter Q.","family":"Ralston","sequence":"first","affiliation":[{"name":"Department of Biomedical and Translational Sciences, Cornell University, Ithaca, NY, USA"},{"name":"Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-1399","authenticated-orcid":false,"given":"Andrea","family":"Flesken-Nikitin","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5854-181X","authenticated-orcid":false,"given":"Dah-Jiun","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2460-7464","authenticated-orcid":false,"given":"Christopher S.","family":"Ashe","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5559-3881","authenticated-orcid":false,"given":"Blaine A.","family":"Harlan","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences, Cornell University, Ithaca, NY, USA"},{"name":"Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Mozammal","family":"Hossain","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek K.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3227-1696","authenticated-orcid":false,"given":"Anna","family":"Yemelyanova","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7199-3837","authenticated-orcid":false,"given":"Elisa","family":"Schmoeckel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Ludwig Maximilians University, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3987-9580","authenticated-orcid":false,"given":"Andrew K.","family":"Godwin","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Mayr","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Ludwig Maximilians University, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2164-350X","authenticated-orcid":false,"given":"Benjamin D.","family":"Cosgrove","sequence":"additional","affiliation":[{"name":"Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3729-7982","authenticated-orcid":false,"given":"Alexander Yu.","family":"Nikitin","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026040208202316000_2026.03.26.714557v1.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70043"},{"key":"2026040208202316000_2026.03.26.714557v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10110433"},{"key":"2026040208202316000_2026.03.26.714557v1.3","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17040604"},{"key":"2026040208202316000_2026.03.26.714557v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/path.2091"},{"key":"2026040208202316000_2026.03.26.714557v1.5","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181cf3d79"},{"key":"2026040208202316000_2026.03.26.714557v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.53"},{"key":"2026040208202316000_2026.03.26.714557v1.7","doi-asserted-by":"publisher","DOI":"10.1097\/pgp.0000000000001121"},{"key":"2026040208202316000_2026.03.26.714557v1.8","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000213335.40358.47"},{"key":"2026040208202316000_2026.03.26.714557v1.9","doi-asserted-by":"publisher","DOI":"10.1242\/dev.149989"},{"key":"2026040208202316000_2026.03.26.714557v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.10.013"},{"key":"2026040208202316000_2026.03.26.714557v1.11","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.047035"},{"key":"2026040208202316000_2026.03.26.714557v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52984-1"},{"key":"2026040208202316000_2026.03.26.714557v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.01.003"},{"key":"2026040208202316000_2026.03.26.714557v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108978"},{"key":"2026040208202316000_2026.03.26.714557v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.02.017"},{"key":"2026040208202316000_2026.03.26.714557v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111838"},{"key":"2026040208202316000_2026.03.26.714557v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-07871-w"},{"key":"2026040208202316000_2026.03.26.714557v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(71)92335-x"},{"key":"2026040208202316000_2026.03.26.714557v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1207"},{"key":"2026040208202316000_2026.03.26.714557v1.20","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-24-1366"},{"key":"2026040208202316000_2026.03.26.714557v1.21","doi-asserted-by":"publisher","DOI":"10.7554\/elife.66747"},{"key":"2026040208202316000_2026.03.26.714557v1.22","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioab043"},{"key":"2026040208202316000_2026.03.26.714557v1.23","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-4-41"},{"key":"2026040208202316000_2026.03.26.714557v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0969-x"},{"key":"2026040208202316000_2026.03.26.714557v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859"},{"key":"2026040208202316000_2026.03.26.714557v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4150"},{"key":"2026040208202316000_2026.03.26.714557v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0336-3"},{"key":"2026040208202316000_2026.03.26.714557v1.28","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-11-0107"},{"key":"2026040208202316000_2026.03.26.714557v1.29","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1207"},{"key":"2026040208202316000_2026.03.26.714557v1.30","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-12-60"},{"key":"2026040208202316000_2026.03.26.714557v1.31","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241210154"},{"key":"2026040208202316000_2026.03.26.714557v1.32","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-016-2426-6"},{"key":"2026040208202316000_2026.03.26.714557v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.110408"},{"key":"2026040208202316000_2026.03.26.714557v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51481-9"},{"key":"2026040208202316000_2026.03.26.714557v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01501-9"},{"key":"2026040208202316000_2026.03.26.714557v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05394-6"},{"key":"2026040208202316000_2026.03.26.714557v1.37","doi-asserted-by":"publisher","DOI":"10.1097\/pas.0000000000002414"},{"key":"2026040208202316000_2026.03.26.714557v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66556-y"},{"key":"2026040208202316000_2026.03.26.714557v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9989"},{"key":"2026040208202316000_2026.03.26.714557v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.06.043"},{"key":"2026040208202316000_2026.03.26.714557v1.41","doi-asserted-by":"publisher","DOI":"10.7554\/elife.48994"},{"key":"2026040208202316000_2026.03.26.714557v1.42","doi-asserted-by":"publisher","DOI":"10.3791\/54444"},{"key":"2026040208202316000_2026.03.26.714557v1.43","first-page":"3459","article-title":"Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium","volume":"63","year":"2003","journal-title":"Cancer Res"},{"key":"2026040208202316000_2026.03.26.714557v1.44","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.15.1870"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.26.714557","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:20:38Z","timestamp":1775143238000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.26.714557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":44,"URL":"https:\/\/doi.org\/10.64898\/2026.03.26.714557","relation":{},"subject":[],"published":{"date-parts":[[2026,3,30]]},"subtype":"preprint"}}