RNA-seq expression profiling of ductal macrophages and antigen presenting cells from virgin mouse mammary glands
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE119869 | GEO | 2020/04/01
REPOSITORIES: GEO
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:Macrophages are diverse immune cells that reside in all tissues. Although macrophages have been implicated in mammary gland function, their diversity has not been fully addressed. By exploiting high-resolution 3D imaging and flow cytometry, we have identified a unique population of tissue-resident ductal macrophages (DMs) that form a contiguous network between the luminal and basal layers of the entire mammary gland throughout post-natal development. DMs are long-lived and constantly survey the epithelium though dendrite movement based on advanced 3D intravital imaging. While they initially originate from embryonic precursors, DMs derive from monocytes as they expand during puberty. Moreover, they undergo proliferation in pregnancy to maintain complete coverage of the epithelium in lactation, where they are poised to phagocytose milk-producing cells post-lactation and facilitate remodelling. Interestingly, DMs strongly resemble mammary tumour macrophages and form a network that pervades the tumour epithelium. Thus, the mammary epithelium programs specialised resident macrophages in both physiological and tumorigenic contexts. To explore expression changes as DMs profilerate in pregnancy and lactation, we sorted DMs from the mouse mammary glands of virgin, pregnant, lactating and post-weaning mice and undertook RNA-seq profiling. Results from this data series are shown in Figure 5 of Dawson et al (2020).
2022-02-25 | GSE135615 | GEO
Project description:The mammary gland is unique in female mammals. Mammary tissue undergoes development and remodeling during lactation, a stage associated with high susceptibility to bacterial infections, inducing an inflammatory condition called mastitis. Although the immune response of the mammary gland has been the subject of intense research to improve prevention and treatment efficacy, the precise definition of its immune composition at this particular physiological stage is still missing. We combined single-cell RNA-Seq, flow cytometry, and three-dimensional confocal microscopy techniques to characterize the immune landscape of lactating murine mammary tissue. Macrophages dominated the immune cell repertoire and could be subdivided into at least two subsets: ductal and stromal macrophages. Ductal macrophages represented approximately 80% of the total CD45pos immune cells and co-expressed F4/80 and CD11c, with high levels of MHC class II molecules. They were strategically poised below the alveolar basal cells in contact with the myoepithelial cell network. Adaptive T and B lymphocytes were remarkably less numerous at this stage, which could explain the limited efficacy of vaccination against mastitis. These results support the view that new strategies to increase mammary immunity and prevent mastitis should be devised.
2021-09-13 | GSE183919 | GEO
Project description:Macrophages are diverse immune cells that reside in all tissues. Although macrophages have been implicated in mammary gland function, their diversity has not been fully addressed. By exploiting high-resolution 3D imaging and flow cytometry, we have identified a unique population of tissue-resident ductal macrophages (DMs) that form a contiguous network between the luminal and basal layers of the entire mammary gland throughout post-natal development. DMs are long-lived and constantly survey the epithelium though dendrite movement based on advanced 3D intravital imaging. While they initially originate from embryonic precursors, DMs derive from monocytes as they expand during puberty. Moreover, they undergo proliferation in pregnancy to maintain complete coverage of the epithelium in lactation, where they are poised to phagocytose milk-producing cells post-lactation and facilitate remodelling. Interestingly, DMs strongly resemble mammary tumour macrophages and form a network that pervades the tumour epithelium. Thus, the mammary epithelium programs specialised resident macrophages in both physiological and tumorigenic contexts. RNA-seq profiling demonstrates that DMs have a distinct gene expression signature from stromal macrophages or mammary-resident antigen-presenting cells and that substantial expression changes occur as DMs proliferate during pregnancy and lactation. This SuperSeries is composed of the SubSeries listed below.
2022-02-26 | GSE197493 | GEO
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:Identify gene expression changes in the absence of Plk2 Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and is a putative tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development and as a tumor suppressor in mammary tumorigenesis. Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and is a putative tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development and as a tumor suppressor in mammary tumorigenesis. Comparison between Plk2 +/+ (n=3) and Plk2 -/- (n=3) mouse mammary epithelial cells
2014-05-20 | E-GEOD-50003 | biostudies-arrayexpress
Project description:Mammary gland branching morphogenesis is thought to depend on the mobilization of proteolytic machinery from the matrix metalloproteinase (MMP) family, namely MT1-MMP/MMP14, to drive coordinated epithelial cell invasion through the interstitial extracellular matrix, but the dominant effector has remained undefined. Unexpectedly, we find MMP14 controls postnatal mammary gland branching from the periductal stroma. Transcriptome profiling of stromal cell-targeted mammary glands was used to characterize the impact of stromal Mmp14-targeting on the growth factor and signaling cascades implicated in mammary gland morphogenesis. Transcriptome profiling of ductal networks and associated stroma was used to investigate the functional roles of MMP14 in the postnatal mammary gland stroma in an unbiased fashion.
2019-03-01 | GSE79088 | GEO
Project description:Identify gene expression changes in the absence of Plk2 Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and is a putative tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development and as a tumor suppressor in mammary tumorigenesis. Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and is a putative tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development and as a tumor suppressor in mammary tumorigenesis.
2014-05-20 | GSE50003 | GEO
Project description:Previously we have demonstrated that inactivation of retinoic acid receptor beta (Rarb) in the mouse results in a protective effect against ErbB2-induced mammary gland tumorigenesis although Rarb has been reported as a tumor suppressor before. In the current study, we further confirmed that ablation of Rarb has a very similar impact on Wnt1-induced mammary gland tumorigenesis as those on ErbB2-induced mammary gland tumorigenesis. Nevertheless, the mechanisms by which Rarb confers its effects on tumor progression is quite different although both involving in tumor microenvironment (TME) remodeling. In the Wnt1 tumors, ectopic wnt1 produced by malignant luminal cells activates nearby stromal cells by a paracrine manner. In return, the stromal cells secreted IGF1 to regulate the growth of tumor cells. There is a need of Rarb expression in this interaction. Deletion of Rarb inhibits both wnt1/β-catenin signaling and IGF1/Akt axis in the myoepithelial tumor cells which results in the suppression of epithelial-mesenchymal transition (EMT) in these tumors. Since wnt1 tumors resemble basal-like breast cancer with a poor clinical prognosis in which EMT is one of the most important way for tumor cells to survive against standard treatment and to go to metastasis, we propose that (1) the stromal gene expression signature of Rarb ablation in wnt1 tumors could have some clinical value in predicting the breast cancer outcome; and (2) Rarb antagonist might be a potential therapeutic strategy in EMT-driven aggressive cancers such as basal-like breast cancer. Laser capture microdissection (LCM) was performed to separate the mammary tumor samples into epithelial cell compartment and stromal cell compartment. Transcriptional profiling of the two compartments were investigated by microarray analysis.
2014-10-23 | E-GEOD-56391 | biostudies-arrayexpress
Project description:Tissue remodeling and cell plasticity in the mammary gland are activated by multi-lineage communications. However, the dynamic signaling promoting breast cancer remains unclear. Here, by RNA-sequencing of single cells and physically interacting cells (PIC-seq) along mammary gland development and carcinogenesis, we uncovered that neutrophils appear transiently during early development and re-emerge in physical interaction with tumor cells in advanced carcinoma. Neutrophil heterogeneity analysis characterized transcriptional states linked to age and cancer stage. Integrating ligand-receptor and PIC-seq analyses with various functional experiments unveiled a physical and secreted pro-tumorigenic signaling niche. This approach revealed that neutrophils are recruited by ductal macrophages and physically interact with tumor cells, increasing tumor cell proliferative and invasive properties, as well as endothelial proliferation and angiogenesis. The molecular program upregulated in neutrophil-PICs correlates with lower survival in advanced breast cancer patients. Our interaction-driven perspective highlights potential molecular targets and biomarkers for breast cancer treatment.
2024-12-22 | GSE278570 | GEO