Resident macrophages promote homeostasis of hyaluronan-associated extracellular matrix in the mammary gland stroma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA623511 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11497155_1.fastq.gz | Fastqsanger.gz | |||
| SRR11497155_2.fastq.gz | Fastqsanger.gz | |||
| SRR11497156_1.fastq.gz | Fastqsanger.gz | |||
| SRR11497156_2.fastq.gz | Fastqsanger.gz | |||
| SRR11497157_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Tissue resident macrophages in the mammary gland are found in close association with epithelial structures and within the adipose stroma, and are important for mammary gland development and tissue homeostasis. While epithelial-associated macrophages have been linked to ductal development, the contributions of stromal macrophages to mammary gland homeostasis remain unknown. Using transcriptional profiling, we identify a distinct resident stromal macrophage subpopulation that is characterized by expression of Lyve-1, a receptor for the extracellular matrix component hyaluronan. This subpopulation is enriched in genes associated with extracellular matrix remodeling and is found to be specifically associated with hyaluronan-rich regions within the mammary stroma. Furthermore, macrophage depletion leads to increased accumulation of hyaluronan-associated extracellular matrix in the mammary stroma. These results demonstrate the presence of a distinct subpopulation of macrophages and provide insights into the functional contributions of these macrophages to stromal homeostasis in the mammary gland.
2020-05-31 | GSE148207 | GEO
Project description:Tissue-resident macrophages in the mammary gland are found in close association with epithelial structures and within the adipose stroma, and are important for mammary gland development and tissue homeostasis. Macrophages have been linked to ductal development in the virgin mammary gland, but less is known regarding the effects of macrophages on the adipose stroma. Using transcriptional profiling and single-cell RNA sequencing approaches, we identify a distinct resident stromal macrophage subpopulation within the mouse nulliparous mammary gland that is characterized by the expression of Lyve-1, a receptor for the extracellular matrix (ECM) component hyaluronan. This subpopulation is enriched in genes associated with ECM remodeling and is specifically associated with hyaluronan-rich regions within the adipose stroma and fibrous capsule of the virgin mammary gland. Furthermore, macrophage depletion leads to enhanced accumulation of hyaluronan-associated ECM in the adipose-associated stroma, indicating that resident macrophages are important for maintaining homeostasis within the nulliparous mammary gland stroma.
| S-EPMC7297528 | biostudies-literature
Project description:Macrophages represent a heterogeneous myeloid population with diverse functions in normal tissues and tumors. While LYVE-1 macrophages have been identified in stromal regions of the normal mammary gland and mammary tumor, their functions in these regions remain unknown. Using a genetic LYVE-1+ macrophage deletion model, we demonstrate that loss of LYVE-1+ macrophages leads to accumulation of the extracellular matrix glycosaminoglycan hyaluronan. Consistent with this finding, we demonstrate that LYVE-1 expression correlates with an increased ability of macrophages to bind, internalize, and degrade hyaluronan. Furthermore, we demonstrate that deletion of LYVE-1+ macrophages results in increased hyaluronan accumulation in mammary tumors, which correlates with reduced tumor growth. Finally, using scRNA-seq, we demonstrate that deletion of LYVE-1 macrophages in tumors results in a shift in the remaining macrophages towards a pro-inflammatory phenotype. Together, these findings demonstrate that LYVE-1+ macrophages represent an anti-inflammatory macrophage population that contributes to tissue remodeling in the tumor microenvironment.
2024-06-05 | GSE241469 | GEO
Project description:Adipose stroma in the mouse mammary gland undergoes remodeling throughout the 5 stages of development. These include nulliparous (virgin;never been pregnant), pregnant, lactating, involuting and regressed. We used a microarry to determine the changes in gene expression during gland development.
2013-12-06 | GSE53044 | GEO
Project description:Background: The extracellular matrix provides organizational context for solid organs. During disease, such as acute myocardial infarction, the composition of the extracellular matrix changes remarkably. One of the most notable changes in the extracellular matrix is in the accumulation of collagen; however, hyaluronan rivals collagen in terms of its abundance. Yet, the extent to which specific cells and enzymes may contribute to such accumulation has been largely unexplored. Here, we hypothesized that activated cardiac fibroblasts produce hyaluronan via hyaluronan synthase 2 (HAS2). Methods and Results: Using immunofluorescence, biochemical extraction, and ELISA, we show that hyaluronan accumulates following myocardial infarction and persists through at least four weeks. Our analyses of failing heart RNA sequencing data suggest fibroblasts are the cells most changed in expression of HAS2. Given these insights, we used HAS2 gain- and loss-of-function approaches to examine the extent to which activated cardiac fibroblasts produced hyaluronan. TGF-induced activation of fibroblasts caused a significant increase in Has2 mRNA and concomitant accumulation of hyaluronan greater than 1 MDa in size. Deletion of Has2 abrogated TGF-induced production of hyaluronan. In addition, overexpression of Has2 was sufficient to cause an increase in hyaluronan accumulation in the absence of TGF-induced activation. Given the magnitude of hyaluronan production, and that hyaluronan has been reported to have biologic activity, we then queried whether the primary functions of fibroblasts (proliferation, migration, and collagen production) were impacted by hyaluronan treatment. Our data indicated negligible impacts of Has2 on proliferation, migration, and collagen production. Exposing fibroblasts to exogenous hyaluronan also had minimal impact on fibroblasts. We also assessed whether fibroblast-borne Hyal2 plays a role in degradation of hyaluronan, and our data indicated little impact of Hyal2 on hyaluronan accumulation (or even any impacts on the transcriptional profile of fibroblasts). Conclusion: Activated fibroblasts produce high molecular weight hyaluronan, and the production of hyaluronan depends on Has2. The robust production of hyaluronan by fibroblasts does not appear to impact fibroblast function.
2026-01-30 | GSE284092 | GEO
Project description:Adipose stroma in the mouse mammary gland undergoes remodeling throughout the 5 stages of development. These include nulliparous (virgin;never been pregnant), pregnant, lactating, involuting and regressed. We used a microarry to determine the changes in gene expression during gland development. Mouse mammary glands were selected at three developmental stages for RNA extraction and hybridization on Affymetrix microarrays.
2013-12-06 | E-GEOD-53044 | biostudies-arrayexpress
Project description:Background: The extracellular matrix provides organizational context for solid organs. During disease, such as acute myocardial infarction, the composition of the extracellular matrix changes remarkably. One of the most notable changes in the extracellular matrix is in the accumulation of collagen; however, hyaluronan rivals collagen in terms of its abundance. Yet, the extent to which specific cells and enzymes may contribute to such accumulation has been largely unexplored. Here, we hypothesized that activated cardiac fibroblasts produce hyaluronan via hyaluronan synthase 2 (HAS2). Methods and Results: Using immunofluorescence, biochemical extraction, and ELISA, we show that hyaluronan accumulates following myocardial infarction and persists through at least four weeks. Our analyses of failing heart RNA sequencing data suggest fibroblasts are the cells most changed in expression of HAS2. Given these insights, we used HAS2 gain- and loss-of-function approaches to examine the extent to which activated cardiac fibroblasts produced hyaluronan. TGF-induced activation of fibroblasts caused a significant increase in Has2 mRNA and concomitant accumulation of hyaluronan greater than 1 MDa in size. Deletion of Has2 abrogated TGF-induced production of hyaluronan. In addition, overexpression of Has2 was sufficient to cause an increase in hyaluronan accumulation in the absence of TGF-induced activation. Given the magnitude of hyaluronan production, and that hyaluronan has been reported to have biologic activity, we then queried whether the primary functions of fibroblasts (proliferation, migration, and collagen production) were impacted by hyaluronan treatment. Our data indicated negligible impacts of Has2 on proliferation, migration, and collagen production. Exposing fibroblasts to exogenous hyaluronan also had minimal impact on fibroblasts. We also assessed whether fibroblast-borne Hyal2 plays a role in degradation of hyaluronan, and our data indicated little impact of Hyal2 on hyaluronan accumulation (or even any impacts on the transcriptional profile of fibroblasts). Conclusion: Activated fibroblasts produce high molecular weight hyaluronan, and the production of hyaluronan depends on Has2. The robust production of hyaluronan by fibroblasts does not appear to impact fibroblast function.
2026-01-30 | GSE284157 | GEO
Project description:Background: The extracellular matrix provides organizational context for solid organs. During disease, such as acute myocardial infarction, the composition of the extracellular matrix changes remarkably. One of the most notable changes in the extracellular matrix is in the accumulation of collagen; however, hyaluronan rivals collagen in terms of its abundance. Yet, the extent to which specific cells and enzymes may contribute to such accumulation has been largely unexplored. Here, we hypothesized that activated cardiac fibroblasts produce hyaluronan via hyaluronan synthase 2 (HAS2). Methods and Results: Using immunofluorescence, biochemical extraction, and ELISA, we show that hyaluronan accumulates following myocardial infarction and persists through at least four weeks. Our analyses of failing heart RNA sequencing data suggest fibroblasts are the cells most changed in expression of HAS2. Given these insights, we used HAS2 gain- and loss-of-function approaches to examine the extent to which activated cardiac fibroblasts produced hyaluronan. TGF-induced activation of fibroblasts caused a significant increase in Has2 mRNA and concomitant accumulation of hyaluronan greater than 1 MDa in size. Deletion of Has2 abrogated TGF-induced production of hyaluronan. In addition, overexpression of Has2 was sufficient to cause an increase in hyaluronan accumulation in the absence of TGF-induced activation. Given the magnitude of hyaluronan production, and that hyaluronan has been reported to have biologic activity, we then queried whether the primary functions of fibroblasts (proliferation, migration, and collagen production) were impacted by hyaluronan treatment. Our data indicated negligible impacts of Has2 on proliferation, migration, and collagen production. Exposing fibroblasts to exogenous hyaluronan also had minimal impact on fibroblasts. We also assessed whether fibroblast-borne Hyal2 plays a role in degradation of hyaluronan, and our data indicated little impact of Hyal2 on hyaluronan accumulation (or even any impacts on the transcriptional profile of fibroblasts). Conclusion: Activated fibroblasts produce high molecular weight hyaluronan, and the production of hyaluronan depends on Has2. The robust production of hyaluronan by fibroblasts does not appear to impact fibroblast function.
2026-01-30 | GSE284546 | GEO
Project description:The extracellular matrix (ECM) is biochemically and biomechanically important for the structure and function of the mammary gland, which undergoes vast structural changes throughout pubertal and reproductive development. Although hyaluronan (HA) is a ubiquitous glycosaminoglycan (GAG) of the mammary gland ECM, extensive characterization of HA deposition in the mammary gland is lacking. Understanding physiologic HA metabolism is critical as this tightly controlled system is often hijacked in cancer. In the current studies, we characterize HA regulation throughout mammary gland development to better understand subsequent dysregulation of HA in mammary tumors. Using immunofluorescence (IF) imaging, we demonstrate that organized HA-rich septa exist in the mammary gland stroma throughout puberty, pregnancy, and involution. Furthermore, we find heterogeneous HA deposition within two murine models of breast cancer. Using cell specific isolation techniques, we characterize expression of genes associated with HA binding, synthesis, and degradation within EpCAM + epithelial cells, CD90.2 + fibroblasts, and F4/80 + macrophages isolated from mammary glands and tumors. Most notably, we identify elevated levels of the hyaluronidases Hyal1 and Hyal2 in tumor-association macrophages (TAMs), suggesting a role for TAM-mediated turnover of HA in the tumor microenvironment (TME). Gene expression is supported functionally by in vitro experiments in which macrophages treated with tumor-cell conditioned media exhibit increased hyaluronidase activity. These findings link TAMs to the direct degradation of HA within the TME of mammary tumors, which has negative implications for patient survival.
| S-EPMC9892096 | biostudies-literature
Project description:BACKGROUND:In utero endocrine disruption is linked to increased risk of breast cancer later in life. Despite numerous studies establishing this linkage, the long-term molecular changes that predispose mammary cells to carcinogenic transformation are unknown. Herein, we investigated how endocrine disrupting compounds (EDCs) drive changes within the stroma that can contribute to breast cancer susceptibility. METHODS:We utilized bisphenol A (BPA) as a model of estrogenic endocrine disruption to analyze the long-term consequences in the stroma. Deregulated genes were identified by RNA-seq transcriptional profiling of adult primary fibroblasts, isolated from female mice exposed to in utero BPA. Collagen staining, collagen imaging techniques, and permeability assays were used to characterize changes to the extracellular matrix. Finally, gland stiffness tests were performed on exposed and control mammary glands. RESULTS:We identified significant transcriptional deregulation of adult fibroblasts exposed to in utero BPA. Deregulated genes were associated with cancer pathways and specifically extracellular matrix composition. Multiple collagen genes were more highly expressed in the BPA-exposed fibroblasts resulting in increased collagen deposition in the adult mammary gland. This transcriptional reprogramming of BPA-exposed fibroblasts generates a less permeable extracellular matrix and a stiffer mammary gland. These phenotypes were only observed in adult 12-week-old, but not 4-week-old, mice. Additionally, diethylstilbestrol, known to increase breast cancer risk in humans, also increases gland stiffness similar to BPA, while bisphenol S does not. CONCLUSIONS:As breast stiffness, extracellular matrix density, and collagen deposition have been directly linked to breast cancer risk, these data mechanistically connect EDC exposures to molecular alterations associated with increased disease susceptibility. These alterations develop over time and thus contribute to cancer risk in adulthood.
| S-EPMC7201668 | biostudies-literature