Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1153611 | ENA |
REPOSITORIES: ENA
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Project description:Maternal ancestry reveals cyclical aging of the mammary gland.
| PRJNA1153605 | ENA
Project description:the present provocative data that in addition to the expected progressive age-related involution, mammary gland aging can occur in a cyclical pattern and is dictated by maternal ancestry. In cyclical aging, mammary glands of 11 and 19 months old mice share genetic and proteomic signatures, which are enriched in breast cancer-related pathways, but are absent at 3 and 14 months. Since incidence of breast cancer shows a bimodal age distribution at 45 (~11m in mice) and 65 (~19m in mice) in human populations, cyclical aging may contribute to these peaks of cancer susceptibility. Conversely, since the mammary glands at 3 and 14 months cluster together hierarchically, the cancer-associated peaks seem separated by a rejuvenation phase. Since cyclical aging is observed in mice with extended lifespan, these findings raise the possibility that if oncogenic mutations are avoided during the pro-oncogenic phases, through its rejuvenation phase, cyclical aging may impact multiple organs leading to extended longevity.
2025-08-01 | GSE275925 | GEO
Project description:Aging of the mammary gland is closely associated with increased susceptibility to breast cancer, yet there have been limited systematic studies of aging-induced alterations within this organ. Here we leveraged the power of high-throughput single-cell RNA-sequencing (scRNA-seq) to generate a detailed transcriptomic atlas of young and aged murine mammary tissues, including both epithelial and stromal cell types. This analysis identified altered proportions and distinct gene expression patterns in multiple cell populations as a consequence of aging, independent of history of pregnancy and hormone cycle. In addition, we detected a rare luminal cell type that expresses both hormone-sensing and alveolar lineage markers as well as a unique gene expression signature. In addition, these cells exhibit a significant decrease in relative abundance with age. Overall, this high-resolution transcriptomic landscape reveals the effects of aging on normal mammary gland physiology and can serve as a valuable resource for understanding aging-associated susceptibility to breast cancer.
2020-12-29 | GSE150580 | GEO
Project description:Breastfeeding is an obligatory requirement of mammalian survival. This fundamental process is associated with the adaptation of maternal physiology including the transformation of the mammary gland into a milk-secreting organ. How maternal immunity contributes to mammary gland remodeling and function remains largely unknown. Here, we show that maternal adaptive immunity plays a critical role in shaping lactogenesis. Specifically, physiological adaptation during pregnancy is associated with thymic involution and a paradoxical enrichment in intraepithelial lymphocyte (IEL) precursors that no longer migrate to the gut, but instead preferentially accumulate within the mammary gland. Within this compartment, IEL precursors differentiate into T-bet-expressing unconventional CD8 lymphocytes with a cytotoxic signature which accumulate within the mammary epithelium in an IL-15-dependent manner. Mammary intra-epithelial lymphocytes control milk production by favoring differentiation and maturation of both contractile and milk-secreting cells, thereby promoting offspring fitness. Altogether, this work uncovers a previously unappreciated contribution of the maternal adaptive immune system in organismal remodeling during pregnancy that is associated with mammary gland development and function.
2025-06-04 | GSE280020 | GEO
Project description:Breastfeeding is an obligatory requirement of mammalian survival. This fundamental process is associated with the remodeling of maternal physiology including the transformation of mammary gland into milk-secreting organ. While adaptive immunity has been associated with the broad control of host physiology, how maternal immunity contributes to organismal remodeling during pregnancy including mammary gland remodeling and function remains largely unknown. Here, we show that maternal adaptive immunity plays a critical role in shaping lactogenesis. Specifically, physiological adaptation to pregnancy is associated with thymic involution and paradoxical enrichment in intraepithelial lymphocyte precursors that no longer migrate to the gut but preferentially accumulate within the mammary gland. Within this compartment the precursors develop as T-bet expressing lymphocytes accumulating within the mammary epithelium in an IL-15 dependent manner. Mammary intra-epithelial lymphocytes control milk production by favoring differentiation of both contractile and milk-secreting cells, thereby affecting offspring fitness. Altogether, this work uncovers a previously unappreciated contribution of the maternal adaptive immune system in organismal remodeling during pregnancy associated with mammary gland development and function.
2025-02-14 | GSE253989 | GEO
Project description:Early-life factors, including nutrition, shape long-term health outcomes. Despite the essential role of lactation in maternal nutritional support, the influence of epigenetic factors on lactation and postnatal growth remains poorly understood. Zinc-finger protein 57 (ZFP57), is an epigenetic regulator of genomic imprinting, a process that directs gene expression based on parental origin, playing a vital role in mammalian prenatal growth. Here, we identify a novel function of ZFP57 in the mammary gland, where it serves as a key modulator of postnatal resource control, independently of imprinted genes. ZFP57 regulates multiple aspects of mammary gland functions, including ductal branching and cellular homeostasis. Its absence leads to significant differential gene expression, related to alveologenesis, lactogenesis and milk synthesis, associated with delayed lactation and altered milk composition. This results in life-long impacts on offspring including the development of metabolic syndrome. Cross-fostering reveals intricate dynamics between mother and offspring during lactation. Pups raised by a dam of a different genotype than their birth-mother exhibit exacerbated metabolic features in adulthood. This study shows a novel mechanism responsible for the programming of offspring long-term health by maternal context.
2025-11-03 | MSV000099723 | MassIVE
Project description:High throughput sequencing of miRNAs collected from tammar milk at different time points of lactation showed high levels of miRNA secreted in milk and allowed the identification of differentially expressed milk miRNAs during the lactation cycle as putative markers of mammary gland activity and functional candidate signals to assist growth and timed development of the young. Comparative analysis of miRNA distribution in milk and blood serum suggests that milk miRNAs are primarily expressed from mammary gland rather than transferred from maternal circulating blood, likely through a new putative exosomal secretory pathway.
2015-09-11 | GSE58941 | GEO
Project description:Aging is one of the pivotal risk factors for cancer, notably in breast cancer with diagnosis striking at the average age of 62. However, the intricate mechanisms underlying aging and breast cancer susceptibility remain unclear. In this study, we depicted a comprehensive single-cell landscape of gene expression (scRNA-seq) and chromatin accessibility (scATAC-seq) of mammary glands from different aged rats. Mechanically, we revealed midkine, a growth factor secreted by basal epithelial cells, which might mediates the age-related mammary changes, as a validation, we treated young rats with midkine for a month and performed the single-cell transcriptome analysis on those mammary glands. We found midkine could largely mediates the transcriptional shift and hyperproliferation of aged epithelial cell by activating PI3K/AKT-SREBF1 signaling. Furthermore, we find the aging-related accumulation of midkine could largely mediated aging-related changes of mammary gland and promoting the tumorigenesis of breast tumors proved using a well-established Nitroso-N-methylurea (NMU)-induced breast cancer rat model. Our finding identify a promising biomarker and intervention target for both mammary aging and tumorigenesis.
2024-08-22 | GSE251833 | GEO
Project description:Aging results in changes in mammary gland cell proportions, gene expression, and chromatin accessibility. Cell types captured include epithelial, immune, and stromal cell types.
2024-09-29 | GSE216542 | GEO
Project description:Maternal Nurtritional Programming in the Ovine Mammary Gland
| PRJNA291187 | ENA