Similar Datasets
Project description:Fibroblasts form a major component of the stroma in normal mammary tissue and breast tumors. Here, we have applied longitudinal single-cell transcriptome profiling of >45,000 fibroblasts in the mouse mammary gland across five different developmental stages and during oncogenesis. In the normal gland, diverse stromal populations were resolved, including lobular-like fibroblasts, committed preadipocytes and adipogenesis-regulatory, as well as cycling fibroblasts in puberty and pregnancy. These specialized cell types appear to emerge from CD34high mesenchymal progenitor cells, accompanied by elevated Hedgehog signaling. During late tumorigenesis, heterogeneous cancer-associated fibroblasts (CAFs) were identified in mouse models of breast cancer, including a population of CD34- myofibroblastic CAFs (myCAFs) that were transcriptionally and phenotypically similar to senescent CAFs. Moreover, Wnt9a was demonstrated to be a regulator of senescence in CD34- myCAFs. These findings reflect a diverse and hierarchically organized stromal compartment in the normal mammary gland that provides a framework to better understand fibroblasts in normal and cancerous states.
| S-SCDT-10_1038-S44318-025-00422-3 | biostudies-other
Project description:Fibroblasts form a major component of the stroma in normal mammary tissue and breast tumors. Here we have applied single-cell transcriptome profiling to characterize fibroblasts in the mouse mammary gland across five different developmental stages and during mammary oncogenesis. In the normal gland, diverse stromal populations were resolved, including lobular-like fibroblasts, committed preadipocytes and adipogenesis-regulatory, as well as cycling fibroblasts in puberty and pregnancy. These specialized cell types appear to emerge from CD34high mesenchymal progenitor cells, accompanied by elevated Hedgehog pathway activity. During late tumorigenesis, diverse cancer-associated fibroblasts were identified in different models of breast cancer, including a population of CD34– myCAFs that were transcriptionally and phenotypically similar to senescent CAFs. Moreover, Wnt9a was demonstrated to be a regulator of senescence in CD34– myCAFs. These findings reflect a diverse and hierarchically organized stromal compartment in the normal mammary gland that provides a framework to better understand fibroblasts in normal and cancerous states.
2025-03-12 | GSE289924 | GEO
Project description:Fibroblasts form a major component of the stroma in normal mammary tissue and breast tumors. Here we have applied single-cell transcriptome profiling to characterize fibroblasts in the mouse mammary gland across five different developmental stages and during mammary oncogenesis. In the normal gland, diverse stromal populations were resolved, including lobular-like fibroblasts, committed preadipocytes and adipogenesis-regulatory, as well as cycling fibroblasts in puberty and pregnancy. These specialized cell types appear to emerge from CD34high mesenchymal progenitor cells, accompanied by elevated Hedgehog pathway activity. During late tumorigenesis, diverse cancer-associated fibroblasts were identified in different models of breast cancer, including a population of CD34– myCAFs that were transcriptionally and phenotypically similar to senescent CAFs. Moreover, Wnt9a was demonstrated to be a regulator of senescence in CD34– myCAFs. These findings reflect a diverse and hierarchically organized stromal compartment in the normal mammary gland that provides a framework to better understand fibroblasts in normal and cancerous states.
2025-03-12 | GSE277228 | GEO
Project description:Changing dynamics of the fibroblast differentiation hierarchy during mammary gland morphogenesis and tumorigenesis
| PRJNA1225302 | ENA
Project description:Changing dynamics of the fibroblast differentiation hierarchy during mammary gland morphogenesis and tumorigenesis [scRNA-Seq I]
| PRJNA1161402 | ENA
Project description:Changing dynamics of the fibroblast differentiation hierarchy during mammary gland morphogenesis and tumorigenesis [scRNA-Seq II]
| PRJNA1225306 | ENA
Project description:The prolyl isomerase cyclophilin A (CypA) regulates the Jak2/Stat5 pathway, which is necessary for mammary differentiation and the pathogenesis of breast cancer. In this study, we assessed the role of this isomerase during mammary gland development and erbB2-driven tumorigenesis. Genetic deletion of CypA resulted in delayed mammary gland morphogenesis and differentiation with corresponding decrease in Jak2/Stat5 activation; mammary gland cross-transplantation confirmed this defect was epithelial in nature. Analysis of mammary stem and progenitor populations revealed significant disruption of epithelial maturation. Loss of CypA in the erbB2 transgenic mouse model revealed a marked increase in mammary tumor latency that correlated with decreased Stat5 activation, associated gene expression, and reduced epithelial cell proliferation. These results demonstrate an important role for CypA in the regulation of Jak2/Stat5-mediated biology in mammary epithelium, identifying this isomerase as a novel target for therapeutic intervention.Significance: These findings reveal cyclophilin A functions in normal mammary epithelial development and ErbB2-driven mammary tumorigenesis and suggest therapies targeting cyclophilin A may be efficacious for breast cancer treatment.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/14/3877/F1.large.jpg Cancer Res; 78(14); 3877-87. ©2018 AACR.
| S-EPMC6050080 | biostudies-literature
Project description:BackgroundMorphogenesis results from the coordination of distinct cell signaling pathways controlling migration, differentiation, apoptosis, and proliferation, along stem/progenitor cell dynamics. To decipher this puzzle, we focused on epithelial-mesenchymal transition (EMT) "master genes". EMT has emerged as a unifying concept, involving cell-cell adhesion, migration and apoptotic pathways. EMT also appears to mingle with stemness. However, very little is known on the physiological role and relevance of EMT master-genes. We addressed this question during mammary morphogenesis. Recently, a link between Slug/Snai2 and stemness has been described in mammary epithelial cells, but EMT master genes actual localization, role and targets during mammary gland morphogenesis are not known and we focused on this basic question.Methodology/principal findingsUsing a Slug-lacZ transgenic model and immunolocalization, we located Slug in a distinct subpopulation covering about 10-20% basal cap and duct cells, mostly cycling cells, coexpressed with basal markers P-cadherin, CK5 and CD49f. During puberty, Slug-deficient mammary epithelium exhibited a delayed development after transplantation, contained less cycling cells, and overexpressed CK8/18, ER, GATA3 and BMI1 genes, linked to luminal lineage. Other EMT master genes were overexpressed, suggesting compensation mechanisms. Gain/loss-of-function in vitro experiments confirmed Slug control of mammary epithelial cell luminal differentiation and proliferation. In addition, they showed that Slug enhances specifically clonal mammosphere emergence and growth, cell motility, and represses apoptosis. Strikingly, Slug-deprived mammary epithelial cells lost their potential to generate secondary clonal mammospheres.Conclusions/significanceWe conclude that Slug pathway controls the growth dynamics of a subpopulation of cycling progenitor basal cells during mammary morphogenesis. Overall, our data better define a key mechanism coordinating cell lineage dynamics and morphogenesis, and provide physiological relevance to broadening EMT pathways.
| S-EPMC3531397 | biostudies-literature
Project description:Hippo signaling pathway is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, apoptosis and stem cell self-renewal. TAZ (transcriptional coactivator with the PDZ-binding motif) is a key downstream effector of the mammalian Hippo pathway. Here, using a transgenic mouse model with mammary-gland-specific expression of constitutively active TAZ, we found that TAZ induction in mammary epithelial cells was associated with an increase in mammary glandular size, which probably resulted from adipocyte hypertrophy. Consistent with its known oncogenic potential, we observed tumor formation in TAZ transgenic mice after administration of the carcinogen 7,12-dimethylbenzanthracene (DMBA) and demonstrated that tumorigenesis was reliant on the presence of TAZ. Our findings establish a previously unknown roles of TAZ in regulating both mammary gland morphogenesis as well as carcinogen-induced mammary tumor formation.
| S-EPMC5915420 | biostudies-literature
Project description:DNA methylation and histone modifications have essential roles in remodeling chromatin structure of genes necessary for multi-lineage differentiation of mammary stem/progenitor cells. The role of this well-defined epigenetic programming is to heritably maintain transcriptional plasticity of these loci over multiple cell divisions in the differentiated progeny. Epigenetic events can be deregulated in progenitor cells chronically exposed to xenoestrogen or inflammatory microenvironment. In addition, epigenetically mediated silencing of genes associated with tumor suppression can take place, resulting in clonal proliferation of undifferentiated or semidifferentiated cells. Alternatively, microRNAs that negatively regulate the expression of their protein-coding targets may become epigenetically repressed, leading to oncogenic expression of these genes. Here we further discuss interactions between DNA methylation and histone modifications that have significant contributions to the differentiation of mammary stem/progenitor cells and to tumor initiation and progression.
| S-EPMC2926750 | biostudies-literature