The omentum, a visceral adipose tissue with critical metabolic, immunological, and stem cell functions is the preferred site for ovarian cancer metastasis. However, its role in maintaining homeostasis and its responses to metastatic colonization remain incompletely understood. Using single-cell transcriptomics, we profile different anatomical regions of the omentum in patients with benign conditions and metastasis. We catalog the benign omentum and observe a stable cell type composition and a preserved stem and progenitor niche. Upon metastatic colonization, we report on increased immune heterogeneity and a concomitant reduction of mesothelial and progenitor cells. The lesser omentum, which is not routinely removed during surgical debulking, is identified as a premetastatic niche characterized by neutrophil infiltration, extracellular trap formation, and the presence of micrometastases. At established metastatic sites, resident cells exhibit cancer-associated phenotypes with regulatory, anti-adipogenic, and immunosuppressive properties. Cellular reprogramming across the omentum is associated with signaling profiles of tumor cells, suggesting potential influences on both proximal and distal tissue regions. This cell atlas illuminates the cellular and molecular determinants of organ homeostasis and reveals a high degree of plasticity and cellular reprogramming promoted by cancer colonization.

Department of Health Sciences and Technology ETH Zurich Zurich Switzerland

Department of Immunology 2nd Medical school Charles University Prague Czech Republic

ETH Zurich Department of Biosystems Science and Engineering Basel Switzerland

ETH Zürich NEXUS Personalized Health Technologies Zürich Switzerland

SIB Swiss Institute of Bioinformatics Zürich Switzerland

Sotio Biotech Prague Czech Republic

Swiss Multi Omics Center PHRT CPAC ETH Zurich Zurich Switzerland

University Hospital Basel and University of Basel Department of Biomedicine Ovarian Cancer Research Basel Switzerland

University Hospital Basel Department of Obstetrics and Gynaecology Basel Switzerland

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