Ovarian cancer metastasis to the human omentum disrupts organ homeostasis and induces fundamental tissue reprogramming. Ovarian cancer metastasis to the human omentum disrupts organ homeostasis and induces fundamental tissue reprogramming

The omentum, a visceral adipose tissue critical for metabolic, immunological, and stem cell functions, is a key site for ovarian cancer metastasis. However, its role in homeostasis and response to metastasis is not fully understood. Using single-cell transcriptomics, we profiled different omental regions in patients with benign conditions and ovarian cancer metastasis. We found that the benign omentum maintains stable cell composition and a stem cell niche. Metastasis led to immune landscape diversification and loss of mesothelial and progenitor cells. The lesser omentum, often spared in surgery, emerged as a premetastatic niche with neutrophil infiltration, NETosis, and micrometastases. Cancer cells orchestrated reprogramming of resident cells, inducing regulatory, anti-adipogenic, and immunosuppressive phenotypes across the omentum. 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. Overall design: Single-cell RNAseq data obtained from human omentum tissue samples of 15 patients at time of diagnosis. Human data raw files wil be available upon request >>Submitter states: Raw data couldn't be included due patient privacy concerns. Requests can be made to the PI for access to the raw data.<<< *************************************************************** Raw sequencing data from human patient samples were not submitted to GEO due to data-protection considerations. Controlled access to the raw files is provided through the European Genome-phenome Archive (EGA; accession EGAD50000002110) via the MF-DAC. ***************************************************************