{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T13:08:52Z","timestamp":1778332132447,"version":"3.51.4"},"posted":{"date-parts":[[2025,8,17]]},"group-title":"Cancer Biology","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T00:00:00Z","timestamp":1755388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH","award":["CA194697-01"],"award-info":[{"award-number":["CA194697-01"]}]},{"name":"NIH","award":["CA255064-01A1"],"award-info":[{"award-number":["CA255064-01A1"]}]},{"name":"NIH","award":["CA263798-01"],"award-info":[{"award-number":["CA263798-01"]}]},{"name":"NIH","award":["T32GM075762"],"award-info":[{"award-number":["T32GM075762"]}]},{"name":"NIH","award":["R35GM142654"],"award-info":[{"award-number":["R35GM142654"]}]},{"DOI":"10.13039\/100004917","name":"CPRIT","doi-asserted-by":"crossref","award":["RR220024"],"award-info":[{"award-number":["RR220024"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004917","name":"CPRIT","doi-asserted-by":"crossref","award":["RP230261"],"award-info":[{"award-number":["RP230261"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004917","name":"CPRIT","doi-asserted-by":"crossref","award":["RP250571"],"award-info":[{"award-number":["RP250571"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Metastasis is an emergent continuum driven by evolving reciprocal adaptations between disseminating tumor cells (DTCs) and specialized niches of different organs. The interplay between intrinsic and niche-driven mechanisms that enable DTCs to survive and home to distant organs in peritoneal ovarian cancer metastasis remains incompletely understood. Here, we present MetTag, a single-cell barcoding and transcriptome profiling approach with single cell clonality barcodes and time-stamped batch identifiers (BC.IDs) to resolve metastasis clonality and temporal dynamics of DTC colonization. Deep sequencing of MetTag barcodes revealed enrichment of early-disseminated clones across metastatic sites, and targeted depletion of pioneer DTCs diminished the outgrowth of subsequent arriving DTCs. Subsequent MetTag-coupled single cell RNA sequencing (scRNA-seq) on ascites and metastasis-bearing omenta revealed a distinct interferon-gamma (IFN\u03b3)-centric transcriptional trajectory selectively enriched among pioneer clones.\n                  <jats:italic>In vivo<\/jats:italic>\n                  CRISPR\/Cas9 screening of niche-specific signatures demonstrated that the tumor-intrinsic IFN\u03b3 response is functionally required for peritoneal metastasis. Knockout of the IFN\u03b3 receptor 1 (\n                  <jats:italic>Ifngr1<\/jats:italic>\n                  ) in the initial pioneer DTCs significantly reduced total metastatic burden, revealing a critical window of time in which IFN\u03b3 signaling shapes the post-seeding metastatic niche (PSMN) and subsequent metastatic evolution. Mechanistically, the tumor-intrinsic IFN\u03b3 response induced Poly(ADP-Ribose) polymerase family member 14 (Parp14) and peritoneal macrophages cooperatively shield DTCs from anoikis by promoting pro-survival signaling. Our study defines the temporal clonal architecture of peritoneal niches and reveals a \u201cfirst come, first served\u201d adaptation principle, where pioneer colonizer fitness determines the success of subsequent colonizers.\n                <\/jats:p>","DOI":"10.1101\/2025.08.13.669778","type":"posted-content","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T05:25:13Z","timestamp":1755494713000},"source":"Crossref","is-referenced-by-count":0,"title":["Tumor-Intrinsic IFN\u03b3 Signaling and Niche Adaptation Drive Early Colonization in Ovarian Cancer Metastasis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6698-2893","authenticated-orcid":false,"given":"Emilija","family":"Aleksandrovic","sequence":"first","affiliation":[{"name":"Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, USA"},{"name":"Harold C. 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Simmons Comprehensive Cancer Center, Dallas, TX, 75235, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, Dallas, TX, 75235, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Harold C. Simmons Comprehensive Cancer Center, Dallas, TX, 75235, USA"},{"name":"Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikitha M.","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, USA"},{"name":"Harold C. 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