Single-Cell RNA-seq Reveals Obesity-Induced Alterations in the BRAC1 Mutant Mammary Tumor Microenvironment
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ABSTRACT:
PROVIDER: PRJNA640665 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12057549.fastq.gz | Fastqsanger.gz | |||
| SRR12057550.fastq.gz | Fastqsanger.gz | |||
| SRR12057551.fastq.gz | Fastqsanger.gz | |||
| SRR12057552.fastq.gz | Fastqsanger.gz |
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Project description:In this study, we conducted single-cell RNA sequencing (scRNA-seq) studies to investigate the impact of high-fat diet (HFD)-induced obesity on transcriptomic landscapes of stromal and immune cells in mammary glands of Brca1-/-;p53+/- mice, an animal breast cancer model. The scRNA-seq profiling data showed that five different subtypes of stromal fibroblasts existed in mouse mammary glands. HFD-induced obesity led to upregulated expression of extracellular matrix (ECM) genes (Col3a1, Col6a3, Eln, and Sparc) and downregulated expression of immunoregulatory genes (Iigp1, Ccl2, and Cxcl10) in these stromal subtype cells. These findings, taken together, suggest that obesity alters the ECM composition and immune ecosystem through modulating the functionality of mammary stromal cells. Moreover, scRNA-seq analysis of mammary immune cells indicated that HFD-induced obesity promoted the generation and/or recruiting of pro-tumorigenic M2 macrophages in mammary glands.
2020-09-08 | GSE152866 | GEO
Project description:Younger age and obesity increase the incidence and rates of metastasis of triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer. The tissue microenvironment, specifically the extracellular matrix (ECM), is known to promote tumor invasion and metastasis. We sought to characterize the effect of both age and obesity on the ECM of mammary fat pads. We used a diet-induced obesity (DIO) model where 10-week-old female mice were fed a high-fat diet (HFD) for 16 weeks or a control chow diet (CD) where time points were every 4 weeks to monitor age and obesity HFD progression. We isolated the mammary fat pads to characterize the ECM at each time point. Utilizing proteomics, we found that the early stages of obesity were sufficient to induce distinct differences in the ECM composition of mammary fat pads that promote TNBC cell invasion. ECM proteins previously implicated in driving TNBC invasion Collagen IV and Collagen VI, were enriched with weight gain. Together these data implicate ECM changes in the primary tumor microenvironment as mechanisms by which age and obesity contribute to breast cancer progression.
2024-06-06 | PXD050250 | Pride
Project description:Age and obesity associated immune dysfunction mammary tumor growth
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Project description:We explored early changes in gene expression in the livers and lungs of the HFD-fed, metastasizing mammary tumor-bearing and obesity-resistant mice mice. These alterations may have led to favorable conditions for both the formation of pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as infiltration and proliferation of metastatic tumor cells.
2012-03-05 | GSE36211 | GEO
Project description:We explored early changes in gene expression in the livers and lungs of the HFD-fed, metastasizing mammary tumor-bearing and obesity-resistant mice mice. These alterations may have led to favorable conditions for both the formation of pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as infiltration and proliferation of metastatic tumor cells. Total RNA was isolated from hepatic and pulmonary tissues of high fat diet fed-4T1 cell-injected mice or high fat diet fed-sham mice. Gene expressions were compared to control diet fed-same conditional mice.
2012-03-05 | E-GEOD-36211 | biostudies-arrayexpress
Project description:Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer [Mammary fat pad, MFP]
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Project description:Estrogen signaling modulates the colon microenvironment during obesity
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Project description:Background Understanding how obesity impacts human mammary adipose tissue (MAT) biology is crucial for deciphering its role in mammary epithelium during both physiological and pathophysiological processes, including breast cancer. Hypertrophic mammary adipocytes and Crown-like Structures are present in MAT of obese patients but whether these changes initiate a fibro-inflammatory response at the tissue level remains insufficiently explored. Objective We aimed to investigate the markers of adipose tissue dysfunction (immune cell infiltration, secretion pattern and fibrosis) in tumor-free MAT of obese versus lean patients Methods Tumor-free MAT were obtained from 61 lean and obese women who underwent mastectomy for breast cancer risk reduction or treatment. Immune and non-immune cell infiltration was determined using flow cytometry. Bulk transcriptomic was used to characterize the phenotype of CD206+ macrophages whose infiltration is increased in obese. Conditioned-medium were prepared from MAT to characterize their secretome and dose adipokines and cytokines by ELISA assay. The extra-cellular matrix (ECM) deposition was evaluated by Masson trichrome staining on cross-stained sections and 3D imaging of red picrosirius-stained tissues. Results We observed an increase in CD206+/HLA-DR+ macrophages in the stromal vascular fraction of MAT from obese patients compared to lean ones. Other immune cell infiltration and endothelial or adipose progenitor cell numbers were similar between groups. Bulk transcriptomics on CD206+ macrophages revealed a significant decrease in ECM component secretion and processing in obese samples. Additionally, no heightened secretion of pro-inflammatory cytokines or MCP-1 was noted in obese samples. ECM characterization indicated an absence of fibrosis, with obese MAT showing reduced collagen secretion and deposition compared to lean counterparts. Conclusions Obesity does not associate with inflammation or fibrosis in MAT, underscoring its unique behavior.
2025-01-07 | PXD050896 | Pride
Project description:BackgroundObesity is a risk factor for breast cancer, and women with obesity that develop breast cancer have a worsened prognosis. Within the mammary gland, obesity causes chronic, macrophage-driven inflammation and adipose tissue fibrosis. Weight loss is a recommended intervention to resolve obesity, but the impact of weight loss on the mammary gland microenvironment and in tumors has not been well identified.MethodsTo examine the effects of weight loss following obesity, mice were fed a high-fat diet for 16 weeks to induce obesity, then switched to a low-fat diet for 6 weeks. We examined changes in immune cells, including fibrocytes, which are myeloid lineage cells that have attributes of both macrophages and myofibroblasts, and collagen deposition within the mammary glands of non-tumor-bearing mice and within the tumors of mice that were transplanted with estrogen receptor alpha positive TC2 tumor cells.ResultsIn formerly obese mice, we observed reduced numbers of crown-like structures and fibrocytes in mammary glands, while collagen deposition was not resolved with weight loss. Following transplant of TC2 tumor cells into the mammary glands of lean, obese, and formerly obese mice, diminished collagen deposition and cancer-associated fibroblasts were observed in tumors from formerly obese mice compared to obese mice. Within tumors of obese mice, increased myeloid-derived suppressor cells and diminished CD8+ T cells were identified, while the microenvironment of tumors of formerly obese mice were more similar to tumors from lean mice. When TC2 tumor cells were mixed with CD11b+CD34+ myeloid progenitor cells, which are the cells of origin for fibrocytes, and transplanted into mammary glands of lean and obese mice, collagen deposition within the tumors of both lean and obese was significantly greater than when tumor cells were mixed with CD11b+CD34- monocytes or total CD45+ immune cells.ConclusionsOverall, these studies demonstrate that weight loss resolved some of the microenvironmental conditions within the mammary gland that may contribute to tumor progression. Additionally, fibrocytes may contribute to early collagen deposition in mammary tumors of obese mice leading to the growth of desmoplastic tumors.
| S-EPMC10693119 | biostudies-literature
Project description:Obesity is a risk factor for breast cancer, and women with obesity that develop breast cancer have a worsened prognosis. Within the mammary gland, obesity causes chronic, macrophage-driven inflammation and adipose tissue fibrosis. To examine the impact of weight loss on the mammary microenvironment, mice were fed high-fat diet to induce obesity, then switched to a low-fat diet. In formerly obese mice, we observed reduced numbers of crown-like structures and fibrocytes in mammary glands, while collagen deposition was not resolved with weight loss. Following transplant of TC2 tumor cells into the mammary glands of lean, obese, and formerly obese mice, diminished collagen deposition and cancer-associated fibroblasts were observed in tumors from formerly obese mice compared to obese mice. When TC2 tumor cells were mixed with CD11b+CD34+ myeloid progenitor cells, collagen deposition within the tumors was significantly greater compared to when tumor cells were mixed with CD11b+CD34- monocytes, suggesting that fibrocytes contribute to early collagen deposition in mammary tumors of obese mice. Overall, these studies show that weight loss resolved some of the microenvironmental conditions within the mammary gland that may contribute to tumor progression.
| S-EPMC10312750 | biostudies-literature