Brown adipocytes can display a mammary basal myoepithelial cell phenotype in vivo
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE93230 | GEO | 2017/01/07
SECONDARY ACCESSION(S): PRJNA360384
REPOSITORIES: GEO
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Project description:Brown adipocytes, muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to Pdgfrα+, Myf5Cre-lineage-marked cells. RNAseq analysis identified Early B Cell Factor-2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2-GFP embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2-expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells. Embryonic fibroblasts, isolated from dorsal body wall of E14.5 Myf5-CrE;mTmG embryos, were further fractionated based on the expression of PDGFRα, Itga7 and Myf5-cre (GFP). Total mRNA profiles from Myf5-cre(GFP)+PDGFRα+ and Myf5-cre(GFP)+PDGFRα-Itga7+ cells were generated by deep sequenceing
2014-09-16 | E-GEOD-60441 | biostudies-arrayexpress
Project description:We analyzed coding transcript abundance in fully differentiated, primary brown adipocytes from murine, interscapular brown adipose tissue of wildtype and UCP1-KO mice.
2018-09-13 | GSE119873 | GEO
Project description:OBJECTIVE:Previous work has suggested that white adipocytes may also show a mammary luminal secretory cell phenotype during lactation. The capacity of brown and beige/brite adipocytes to display a mammary cell phenotype and the levels at which they demonstrate such phenotypes in vivo is currently unknown. METHODS:To investigate the putative adipocyte origin of mammary gland cells, we performed genetic lineage-labeling experiments in BAT and the mammary glands. RESULTS:These studies indicated that the classic brown adipocytes (Ucp1+) and subcutaneous beige/brite adipocytes (Ucp1-/+) were found in the mammary gland during lactation, when they exhibited a mammary myoepithelial phenotype. Up to 2.5% of the anterior dorsal interscapular mammary myoepithelial cell population had a brown adipocyte origin with an adipose and myoepithelial gene signature during lactation. Eliminating these cells, along with all the brown adipocytes, significantly slowed offspring growth, potentially demonstrating their functional importance. Additionally, we showed mammary epithelial lineage Mmtv+ and Krt14+ cells expressed brown adipocyte markers after weaning, demonstrating that mammary gland cells can display an adipose phenotype. CONCLUSIONS:The identification of a brown adipocyte origin of mammary myoepithelial cells provides a novel perspective on the interrelationships between adipocytes and mammary cells with implications for our understanding of obesity and breast cancer.
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Project description:For placental mammals, the transition from the in utero maternal environment to postnatal life requires the activation of thermogenesis to maintain their core temperature. This is primarily accomplished by induction of uncoupling protein 1 (UCP1) in brown and beige adipocytes, the principal sites for uncoupled respiration. Despite its importance, how placental mammals license their thermogenic adipocytes to participate in postnatal uncoupled respiration is not known. Here, we provide evidence that the 'alarmin' IL-33, a nuclear cytokine that activates type 2 immune responses, licenses brown and beige adipocytes for uncoupled respiration. We find that, in absence of IL-33 or ST2, beige and brown adipocytes develop normally but fail to express an appropriately spliced form of Ucp1 mRNA, resulting in absence of UCP1 protein, and impairment in uncoupled respiration and thermoregulation. Together, these data suggest that IL-33 and ST2 function as a developmental switch to license thermogenesis during the perinatal period.
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Project description:Adipose tissue in the mammary gland undergoes dramatic remodeling during reproduction. Adipocytes are replaced by mammary alveolar structures during pregnancy and lactation, then reappear upon weaning. Here, we reveal that adipocytes in the mammary gland de-differentiate into Pdgfrα+ preadipocyte- and fibroblast-like cells during pregnancy, and remain de-differentiated during lactation. Upon weaning, de-differentiated fibroblasts proliferate and re-differentiate into adipocytes. In order to determine the molecular signature of these de-differentiated adipocytes in the mammary gland, we compared these cells with classical adipocytes. Using the AdipoChaser-mT/mG system, we pre-labeled mature adipocytes with GFP expression to characterize the features of these de-differentiated adipocytes (Figure 4A), and then purified CD31-/CD45-/PDGFRα+/Tomato+ and CD31-/CD45-/PDGFRα+/GFP+ cells from the stromal vascular fraction (SVF) of lactating mammary gland at the peak of lactation through FACS. Gene expression analyses showed that the CD31-/CD45-/PDGFRα+/Tomato+ cells were indeed enriched with Tomato expression, while the CD31-/CD45-/PDGFRα+/GFP+ cells were enriched with GFP expression (Figure 4C). We then collected CD31-/CD45-/PDGFRα+/GFP+ cells as single cells for subsequent single cell RNA-sequencing analysis (Figure 4D-G, Supplemental. Figure S1A-G). After the flow sorting and single cell RNA amplification, 26 CD31-/CD45-/PDGFRα+/GFP+ cells passed the quality control, and these cells were used for single-cell RNA-sequencing analysis. Due to technical difficulties in sorting single mature white adipocyte through flow cytometry, adipocytes differentiated from the immortalized murine-derived brown pre-adipocyte cell line were used as mature adipocyte control (Pradhan et al., 2017). Additionally, we also included population RNA-seq experiments, i.e. three mature white adipocyte samples, two GFP+, and six GFP- ones.
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Project description:To investigate the effects of ITGB6 induction of breast myoepithelial cells (1089 and primary myoepithelial cells), we induced expression of ITGB6 utilising the TET-On system for 48 hr.
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Project description:Myoepithelial and luminal cells synergistically expand in the mammary gland during pregnancy, and this process is precisely governed by hormone-related signaling pathways. The BMP signaling pathway is now known to play crucial roles in all organ systems. However, the functions of BMP signaling in the mammary gland remain unclear. Here, we found that Bmpr1a is upregulated by hormone-induced Sp1 at pregnancy. Using a doxycycline (Dox)-inducible Bmpr1a conditional knockout mouse model, we demonstrated that loss of Bmpr1a results in compromised myoepithelial integrity, reduced mammary stem cells and precocious alveolar differentiation during pregnancy. Mechanistically, Bmpr1a regulates the expression of p63 and Slug, two key regulators of myoepithelial maintenance, through pSmad1/5-Smad4 complexes, and consequently activate P-cadherin during pregnancy. Collectively, these findings identify a novel role of BMP signaling in maintaining the identity of myoepithelial cells and suppressing precocious alveolar formation.
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Project description:Obesity has become a global health problem. Brown adipose tissue (BAT), specialized for energy expenditure through thermogenesis, potently counteracts obesity. Recently, BAT is also identified in human adults. We found that Lgr4 homozygous mutant (Lgr4m/m) mice display reduced adiposity and exhibit brown-like adipocytes in their WAT depots with higher expression of uncoupling protein 1 (Ucp1). Furthermore, Lgr4 ablation potentiates brown adipocyte differentiation from stromal vascular fraction (SVF) of epididymal WAT (eWAT) in vitro. We used microarrays to emxamine the gene expression profiles of the brown-like adipocytes differentiated from SVF of wild-type and Lgr4 mutant mice. We identified distinct gene expression profiles of these two groups.
2013-11-07 | GSE47760 | GEO
Project description:Mice and other small mammals heavily rely on UCP1-mediated non-shivering thermogenesis in the cold, and thus the unexpected cold resistance of UCP1-knockout (UCP1KO) mice has always been and still is an unresolved mystery inextricably intertwined with alternative means of thermogenesis and futile substrate cycles. Several potentially thermogenic futile substrate cycles in adipose tissue of WT and UCP1KO mice have been reported in the literature. We hypothesized that isoproterenol treatment of brown adipocytes from UCP1KO mice would cause an immediate acceleration of futile substrate cycling, and entail a consecutive upregulation of the involved enzymes to recruit additional capacity. In this study, we analyzed changes in the proteome of wild type (WT) and UCP1KO adipocytes during acute adrenergic stimulation to detect characteristic molecular signatures, which allowed us to narrow down our search to potential candidates related to Ca2+ and lipid metabolism.
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