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Identification of sex- and inflammation-associated heterogeneity in mouse omentum using single-cell RNA sequencing

ABSTRACT: The omentum is a critical intraperitoneal organ essential for peritoneal homeostasis, yet detailed characterization of its cellular composition remains limited by the lack of validated markers. Here, we employed single-cell RNA sequencing to systematically define cellular heterogeneity in naive and activated mouse omentum from both sexes. Our analysis identified previously uncharacterized immune and stromal cell subsets, including three macrophage subtypes with activation-dependent gene expression patterns, implying specialized roles in inflammation and immune regulation. Comparative analysis revealed marked transcriptional differences between omental and peritoneal macrophages, underscoring tissue-specific microenvironments. Additionally, sexually dimorphic gene expression in omental stromal cells correlated with peritoneal macrophage polarization, indicating sex-specific regulatory mechanisms. Critically, macrophages from omentum of female mice with ovarian cancer metastases showed unique gene signatures associated with tumor migration and invasion. Collectively, we provide the first comprehensive atlas of omental cell populations stratified by sex and activation state, offering novel insights into peritoneal immunity and identifying potential therapeutic targets for inflammatory and metastatic diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE212419 | GEO | 2025/09/25

REPOSITORIES: GEO

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Cellular basis of omentum activation and expansion revealed by single-cell RNA sequencing using a parabiosis model

Project description:Although the physiological function of the omentum remains elusive, it has been proposed that it plays an important role in fat storage, immune regulation, and regeneration of injured tissues and organs. Although the omentum undergoes expansion upon activation, reports on the accurate assessment of increased cell types and the origin of the increased cells remain limited. To investigate this aspect, the omenta of parabiotic mice were subjected to activation using distinct fluorescent markers and single-cell RNA sequencing (scRNA-seq) was performed to identify circulation-derived omental cells. We found that a considerable number of circulating cells contributed to the activation of the omentum. The omental cells derived from circulating cells exhibited morphological features similar to those of fibroblasts. scRNA-seq revealed the existence of a novel cell population that co-expressed macrophage and fibroblast markers in the activated omentum, suggesting that it corresponded to circulating macrophage-derived fibroblast-like cells. Lineage tracing experiments revealed that most fibroblasts in the activated omentum were not derived from WT1-positive mesenchymal progenitors. The cell cluster also expressed various chemokine genes, indicating its role in the activation and recruitment of immune cells. These results provide important information regarding the activation of the omentum.

2021-10-31 | GSE176254 | GEO

Bulk RNA-Sequencing of Murine Normal and Tumor-Associated Omental and Mesenteric Macrophages

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Project description:High-grade serous (HGS) ovarian cancer is the most common and aggressive ovarian cancer type, and the most lethal gynaecological disease 1,2. The major cause is its highly metastatic nature and the limited availability of effective therapies to oppose it. The omentum is a highly vascularised visceral depot of adipose tissue with immune functions, which becomes the preferential metastatic site in patients with HGS ovarian cancer 1,2. The omentum provides an environment that supports the rapid growth of metastatic tumours and their spread within the peritoneal cavity and adjacent organs 2,3. Research aimed at understanding the biology of metastatic tumours in the omentum is therefore essential to find strategies to oppose HGS ovarian cancer. To this aim, there is the need for in vitro models that faithfully recapitulate the microenvironment of HGS omental metastasis in patients.

2023-11-28 | PXD042317 | Pride

Omentum gel enables the study of metastatic ovarian cancer and stromal cell functions in a physiologically relevant environment

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2022-02-22 | PXD011938 | Pride

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