Ductal macrophages predominate in the immune landscape of the lactating mammary gland
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PROVIDER: PRJNA762337 | ENA |
REPOSITORIES: ENA
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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:Background: The mammary gland is a dynamic organ that undergoes important physiological changes during reproductive cycles. Until now, data regarding the characterisation of miRNA in the mammary gland have been scarce and mainly focused on their abnormal expression in breast cancer. Our goal was to characterise the microRNA (miRNA) involved in mechanisms regulating the mammary function, with particular focus on the lactation stage Methodology/principal findings: Using high-throughput sequencing technology, an exhaustive repertoire of miRNA (miRNome) expressed in mouse and bovine mammary glands during established lactation was identified, characterised and compared. Furthermore, in order to obtain more information on miRNA loading in the RNA-induced silencing complex (RISC), the miRNome was compared with that obtained from RNA associated with the AGO2 protein (AGO2-miRNome) in mouse lactating mammary gland. This study enabled the identification of 164 and 167 miRNA in mouse and bovine, respectively. Among the 30 miRNA most highly expressed in each species, 24 were common to both species and six of them tended to be more highly expressed in lactating than in non-lactating mammary gland. The potential functional roles of these 24 miRNA were deduced using DIANA-miRPath software, based on miRNA/mRNA interactions. Moreover, seven putative novel miRNA were identified. Using DAVID analysis, it was concluded that the predicted targets of two of these putative novel miRNA are involved in mammary gland morphogenesis. Conclusion/significance: Our study provides an overview of the characteristics of lactating mouse and bovine mammary gland miRNA expression profiles. Moreover, species-conserved miRNA involved in this fundamental biological function were identified. These miRNomes will new be used as references for further studies during which the impact of animal breeding on the miRNA expression will be analysed.
2014-03-24 | GSE53511 | GEO
Project description:Background: The mammary gland is a dynamic organ that undergoes important physiological changes during reproductive cycles. Until now, data regarding the characterisation of miRNA in the mammary gland have been scarce and mainly focused on their abnormal expression in breast cancer. Our goal was to characterise the microRNA (miRNA) involved in mechanisms regulating the mammary function, with particular focus on the lactation stage Methodology/principal findings: Using high-throughput sequencing technology, an exhaustive repertoire of miRNA (miRNome) expressed in mouse and bovine mammary glands during established lactation was identified, characterised and compared. Furthermore, in order to obtain more information on miRNA loading in the RNA-induced silencing complex (RISC), the miRNome was compared with that obtained from RNA associated with the AGO2 protein (AGO2-miRNome) in mouse lactating mammary gland. This study enabled the identification of 164 and 167 miRNA in mouse and bovine, respectively. Among the 30 miRNA most highly expressed in each species, 24 were common to both species and six of them tended to be more highly expressed in lactating than in non-lactating mammary gland. The potential functional roles of these 24 miRNA were deduced using DIANA-miRPath software, based on miRNA/mRNA interactions. Moreover, seven putative novel miRNA were identified. Using DAVID analysis, it was concluded that the predicted targets of two of these putative novel miRNA are involved in mammary gland morphogenesis. Conclusion/significance: Our study provides an overview of the characteristics of lactating mouse and bovine mammary gland miRNA expression profiles. Moreover, species-conserved miRNA involved in this fundamental biological function were identified. These miRNomes will new be used as references for further studies during which the impact of animal breeding on the miRNA expression will be analysed. microRNA profiles of mammary glands from 2 FVB/N mice at lactation day-12 and mammary biopsies from 4 Holstein dairy cows at mid-lactation, generated by deep sequencing, using Illumina HiSeq 2000.
2014-03-24 | E-GEOD-53511 | biostudies-arrayexpress
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.
| S-EPMC8564477 | biostudies-literature
Project description:Nutrition affects milk composition influencing its nutritional properties. Nutrition also modifies the expression of mammary genes, whose regulation is not completely known. MicroRNAs (miRNA) are small non-coding RNA that work as important post-transcriptional gene expression regulators by targeting messenger RNAs. Our goal was to characterize miRNA whose expression is regulated by nutrition in the lactating goat mammary gland, and which may give clues to decipher the regulations of milk components biosynthesis and secretion. Using high-throughput sequencing technology, miRNomes of the lactating mammary gland have been established from 4 goats fed ad libitum and 6 goats food deprived during 48h. Food deprivation affected the expression of 30 miRNA (padj<0.1), 16 were downregulated and 14 were upregulated. Prediction tools Diana-microT suggests a potential role of several nutriregulated miRNA in the lipid metabolism. Among putative targets 19 differently expressed genes (DEG) previously identified in the same sample, were found. Functions of these 19 DEG revealed their involvement in tissue remodeling. This study constitutes the first evidence of nutriregulated miRNA in the ruminant mammary gland. The characterization of these 30 miRNA could contribute to a better understanding of genes regulations in the mammary gland in response to nutrition.
2015-07-01 | GSE61025 | GEO
Project description:Nutrition affects milk composition influencing its nutritional properties. Nutrition also modifies the expression of mammary genes, whose regulation is not completely known. MicroRNAs (miRNA) are small non-coding RNA that work as important post-transcriptional gene expression regulators by targeting messenger RNAs. Our goal was to characterize miRNA whose expression is regulated by nutrition in the lactating goat mammary gland, and which may give clues to decipher the regulations of milk components biosynthesis and secretion. Using high-throughput sequencing technology, miRNomes of the lactating mammary gland have been established from 4 goats fed ad libitum and 6 goats food deprived during 48h. Food deprivation affected the expression of 30 miRNA (padj<0.1), 16 were downregulated and 14 were upregulated. Prediction tools Diana-microT suggests a potential role of several nutriregulated miRNA in the lipid metabolism. Among putative targets 19 differently expressed genes (DEG) previously identified in the same sample, were found. Functions of these 19 DEG revealed their involvement in tissue remodeling. This study constitutes the first evidence of nutriregulated miRNA in the ruminant mammary gland. The characterization of these 30 miRNA could contribute to a better understanding of genes regulations in the mammary gland in response to nutrition. MicroRNA profiles of mammary glands from 10 Alpine goats at the peak of lactation (48 ± 2 days post-partum) generated by a HiSeq 2500 using Illumina Solexa technic.
2015-07-01 | E-GEOD-61025 | biostudies-arrayexpress
Project description:The goal of this study is to improve the quality, efficiency, and sustainability of milk production by improving the understanding of the function of cis-regulatory elements in regulating the bovine mammary gland. To this end, we have characterized the non-lactating and lactating mammary gland transcriptomes by whole transcriptome shotgun sequencing (RNA-seq). We will identify cis-regulatory elements in the non-lactating and lactating bovine mammary gland genome-wide. Finally, we will annotate and characterize mammary gland cis-regulatory elements by computational analysis and identify high-resolution genome-wide in vivo footprints of diverse trans-acting-factors (TF), over-represented TF bindings sites and overlapping SNPs.
2021-04-06 | GSE116079 | GEO
Project description:Cross-species hybridization analysis of mammary glands during pregnancy and lactation. Results provide insight into putative conserved molecular mechanisms regulating mammary gland development. This study was performed to identify orthologous transcripts that are differentially co-expressed in the mammary gland at 2 stages of development (pregnancy and lactation) in wild type Sprague-Dawley rats. Key points are examined in a time series of Sprague Dawley rat mammary gland development, secretory activation and lactation. Triplicate rat (three biological replicates) at each time point were used for statistical power totalling 12 individual arrays in this study. Rats were as staged pregnant day 1 the day that post coital plug was observed, and similarly, lactation day 1 was the first day after birth. Whole mammary glands No. 4 (inguinal) were obtained from female rats at stages of development: virgin (adulthood, 14 wks of age), Pregnant (5 and 14 days of pregnancy) and Lactating (day 1 and 12 postpartum). The two-color (Cy5/Cy3) microarray experiment was designed to hybridize samples from each group against a common reference, a pool of RNA from mammary gland of three parous or virgin female rats.
2013-10-30 | E-GEOD-22545 | biostudies-arrayexpress
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:Background : In lactating cow, a sunflower oil supplementation modulated the milk composition and the mammary genes expression whose mechanisms of regulations are unclear. Results : This lipid supplementation provoke, in mammary gland, the down regulation of microRNA miR-20a-5p and miR-142-5p, which are predicted to target genes previously determined as differentially expressed including those involved in lipid metabolism. Conclusion : Those two miRNA are good candidates to explain lipogenic genes regulations after sunflower oil supplementation. Significance : The current study clarified the nutriregulation of miRNA in the mammary gland.
2016-07-01 | GSE81616 | GEO