{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:04:06Z","timestamp":1784045046032,"version":"3.55.0"},"posted":{"date-parts":[[2026,4,24]]},"group-title":"Cancer Biology","reference-count":128,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Cancer Institute Cancer Center Support Grant","award":["5P30CA045508"],"award-info":[{"award-number":["5P30CA045508"]}]},{"name":"National Cancer Institute","award":["R37CA292807"],"award-info":[{"award-number":["R37CA292807"]}]},{"name":"Oliver S. and Jennie R. Donaldson Charitable Trust"},{"DOI":"10.13039\/100014599","name":"Mark Foundation for Cancer Research","doi-asserted-by":"crossref","award":["20-028-EDV"],"award-info":[{"award-number":["20-028-EDV"]}],"id":[{"id":"10.13039\/100014599","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cold Spring Harbor Laboratory and Northwell Health Affiliation"},{"name":"New York Genome Center Polyethnic-1000 Initiative"},{"name":"Beverly Hazelkorn Uterine Cancer Research Foundation"},{"name":"Foundation for Women\u2019s Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Uterine carcinosarcoma (UCS) is an aggressive endometrial cancer defined by coexisting malignant epithelial and mesenchymal components, rapid metastatic dissemination, and poor therapeutic response. However, its cellular ecosystem remains poorly resolved, particularly in patients of African ancestry who are underrepresented in genomic datasets despite a disproportionate disease burden. Here, we generated a single-cell atlas of 15 primary and metastatic UCS specimens from a diverse cohort of 13 patients enriched for African ancestry, integrated with whole-genome sequencing. Malignant cells exhibited epithelial-like, mesenchymal-like, transitional, and stem\/progenitor-like states within individual tumors that mapped to patient-specific copy number-defined subclones and RNA-velocity trajectories, supporting metaplastic state transitions. Compared to normal endometrium, primary tumors were enriched for epithelial-mesenchymal-transition (EMT), mTORC1, and glycolytic programs, whereas matched metastases show enhanced TNF\u03b1-NF\u03baB-associated invasive programs. The tumor microenvironment contained immunosuppressive myeloid states and diverse cancer-associated fibroblast (CAF) subsets, including pericyte-like and matrix-remodeling subsets that act as predicted communication hubs through chemokine and immune-checkpoint circuits. We found a CAF-centered CCL2-CXCL1\/2-IL10 module linked to CD8 T-cell dysfunction and a TIGIT-CD96-PVR checkpoint module. These data define the UCS cellular ecosystem in which malignant plasticity is coupled to stromal-immune cell remodeling in a patient cohort of enriched ancestries and nominate stromal-immune axes for further therapeutic investigation.<\/jats:p>","DOI":"10.64898\/2026.04.21.720013","type":"posted-content","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T22:45:12Z","timestamp":1777070712000},"source":"Crossref","is-referenced-by-count":1,"title":["A Single-Cell Atlas Reveals Cancer Cell Plasticity and Stromal-Immune Remodeling in Uterine Carcinosarcoma Across Diverse Ancestries"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0077-4597","authenticated-orcid":false,"given":"Santhilal","family":"Subhash","sequence":"first","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA"},{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Jammu, Jammu, 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Hofstra\/Northwell, New Hyde Park, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arielle","family":"Katcher","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Northwell Health, Zucker School of Medicine at Hofstra\/Northwell, New Hyde Park, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Chung","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA"},{"name":"Graduate Program in Genetics, Stony Brook University, Stony Brook, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyom","family":"Shah","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Ozcelik","sequence":"additional","affiliation":[{"name":"Cold 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