ArticleDiscover oncology2025
Single-cell RNA sequencing reveals the potential role of estrogen in tuberous sclerosis complex related renal angiomyolipoma.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- The role of the nervous system in the occurrence, development, and immune response of renal cell carcinoma.Frontiers in immunology · 2025Review
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11 authors.
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Abstract
purposeTuberous sclerosis complex (TSC) is a kind of rare genetic disorder caused by TSC1/TSC2 gene mutations and presented as angiomyolipoma (AML) in kidney. Previous studies have indicated the presence of estrogen-related heterogeneity in TSC, but this aspect has not been extensively explored.
methodsIn the present study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the estrogen-related heterogeneity in TSC-AML. A total of two female and two male TSC-AML patients were included in this study.
resultsOur results revealed the presence of various cell types within the TSC-AML tissue, including macrophages, endothelial cells, dendritic cells, neutrophils, B cells, fibroblasts, and tumor cells. Among the macrophage population, the immune-suppressive C1QC-Macro cells constituted the majority, and these cells were found to be more prevalent in female patients. AUCell analysis showed that estrogen-related pathways were significantly upregulated in C1QC-Macro cells in female patients compared to male patients. Furthermore, CellChat analysis demonstrated that tumor cells in female patients may regulate C1QC-Macro cells through the CXCL signaling pathway (CXCL12-CXCR4). In contrast, male patients exhibited enhanced interactions in stromal remodeling-related signaling pathways. Tumor cells were further categorized into TC1-TC6 subtypes. Notably, tumor cells with stem cell-like and EMT (epithelial-mesenchymal transition) characteristics were more common in male patients, whereas adipose-like, SMC-like, immune-suppressive, and fatty acid uptake-related tumor cells were more prevalent in female patients. Additionally, estrogen-related transcription factors (TFs), such as ESRRG, CREB1, CREB3L2, and CREB3L4, were activated in the stem cell-like tumor cells of female patients but not in those of male patients, suggesting that estrogen might play an important role in the pathogenesis of TSC-AML in females.
conclusionOur findings indicate that estrogen regulates the formation of an immune-suppressive microenvironment and the development of stem cell-like tumors in female TSC-AML patients.
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