Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reconstruction of Dynamic Mammary Mini Gland in vitro for Normal Physiology and Oncogenesis

ABSTRACT: Organoid culture has been extensively exploited for normal tissue reconstruction and disease modeling, however, it is still challenging to establish physiologically relevant architecture, size and functions in homeostasis. Here, we describe the development of a long-term adult stem cell derived mammary mini-gland culture system that supports robust 3D outgrowths recapitulating the morphology, cellular context, transcriptional heterogeneity of the normal mammary gland. The self-organization ability of stem cells and the stability of the outgrowths were determined by a coordinated combination of extracellular matrix, environmental signalings and dynamic physiological cycles. These mini glands are hormone responsive and reproduce the entire postnatal mammary development including puberty, estrous cycle, lactation and involution. Most intriguingly, these mini glands maintained the mammary stem cells and represented the fate transition from embryonic bipotency to postnatal unipotency in lineage tracing assays. In addition, induced oncogene expression in the mini glands drove the clinically relevant cancer initiation that can be monitored chronologically. Together, this study provides an experimental system fostering a dynamic organ miniature that can be studied chronologically and spatially for physiologically relevant biological processes with complexity.

ORGANISM(S): Mus musculus

PROVIDER: GSE211527 | GEO | 2023/08/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Identification of stem cell populations in sweat glands and ducts: roles in homeostasis and wound repair

Project description:Sweat glands are abundant glands of our body and essential for thermoregulation. Like mammary glands, they originate from epidermal progenitors. However, they display few signs of cellular turnover, and whether they have stem cells and tissue regenerative capacity remain largely unexplored. Here we address these issues. Using lineage-tracing, we identify multipotent progenitors in sweat duct that transition to unipotency after developing the sweat gland. In characterizing four adult stem cell populations of glandular skin, we show that they display distinct regenerative capabilities and remain unipotent when healing epidermal, myoepithelial-specific and luminal-specific injuries. We devise purification schemes, isolate and transcriptionally profile progenitors. Exploiting molecular differences between sweat and mammary glands, we show that only some progenitors regain multipotency to produce de novo ductal and glandular structures, but that these can retain their identity even within certain foreign microenvironments. Our findings provide new concepts about glandular stem cells and sweat gland biology. 10 samples from mouse paw pads were analyzed

2013-01-02 | E-GEOD-37274 | biostudies-arrayexpress

Identification of stem cell populations in sweat glands and ducts: roles in homeostasis and wound repair

2013-01-02 | GSE37274 | GEO

Comparison of Differences in Mouse Mammary gland gene expression data at POSTNATAL DAY 70 in Akt1wildtype versus Akt1-deficient mice

Project description:Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays a critical role in the regulation of several cellular processes including cell proliferation and apoptosis. In this study, we utilized Akt1+/+ and Akt1Â¬-/- C57/Bl6 female mice to demonstrate that Akt1 is required for normal mammary gland postnatal development and homeostasis. Akt1 deficiency resulted in severely delayed postnatal mammary gland growth as well as a significant decrease in the number of terminal end buds during puberty. Adult Akt1-/- mammary glands exhibited significantly fewer alveolar buds coupled with a significant increase in epithelial cell apoptosis compared to their wild-type counterparts. Microarray analysis revealed that Akt1 deficiency resulted in several altered gene expression changes and biological processes in adult mammary glands, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1-/- mammary glands by both microarray and RT-PCR validation. Transcriptome analysis of Akt1 wild type and akt1-homozygous mouse mammary glands wild type mammary glands from 3 mice and Akt1-deficient mammary glands from 3 mice were analyzed for differences in gene expression at postnatal day 70

2011-07-14 | E-GEOD-30671 | biostudies-arrayexpress

Expression array of stromal Mmp14-targeted mammary glands

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

Comparison of Differences in Mouse Mammary gland gene expression data at POSTNATAL DAY 70 in Akt1wildtype versus Akt1-deficient mice

Project description:Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays a critical role in the regulation of several cellular processes including cell proliferation and apoptosis. In this study, we utilized Akt1+/+ and Akt1¬-/- C57/Bl6 female mice to demonstrate that Akt1 is required for normal mammary gland postnatal development and homeostasis. Akt1 deficiency resulted in severely delayed postnatal mammary gland growth as well as a significant decrease in the number of terminal end buds during puberty. Adult Akt1-/- mammary glands exhibited significantly fewer alveolar buds coupled with a significant increase in epithelial cell apoptosis compared to their wild-type counterparts. Microarray analysis revealed that Akt1 deficiency resulted in several altered gene expression changes and biological processes in adult mammary glands, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1-/- mammary glands by both microarray and RT-PCR validation. Transcriptome analysis of Akt1 wild type and akt1-homozygous mouse mammary glands

2011-07-15 | GSE30671 | GEO

Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

Project description:Exposure to estrogen and its mimics during menopausal transition is thought to modify the structure of mammary gland. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary gland tissue was affected by both 17β-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). Three analyzed flame retardants, BDE-47, BDE-100 and BDE-153, are most frequently detected in human serum from all over the world. During physiologically-relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end bud-like structures. According to sequencing analysis of mammary gland RNA, PBDEs both augmented E2-facilitated cell proliferationgene expression changes and modulated immune regulation. To better elucidate the effects of E2 and PBDEs, single-cell RNA sequencing (scRNAseq) analysis was performed. In a definitive manner, E2 was found to induce Pgr expression in both Esr1+ and Esr1- cells. Significantly, molecular evidence was available to show functional differences among cells with differential expression of Esr1 and Pgr. The PBDEs + E2 treatment increased the number of double positive (Esr1+Pgr+) and Pgr only (Esr1-Pgr+) cells in both mature luminal epithelial and progenitor cells of luminal epithelialcells. Moreover, the combination increased the mammary gland population of M2 macrophages. The results help clarify how exposure to both E2 and endocrine disrupting chemicals like PBDEs during menopausal transition impact mammary gland structure. Ultimately, the findings advance understanding of how exposure can increase the risk of developing breast cancer.

2019-11-12 | GSE125272 | GEO

Mouse Mammary Gland Morphogenic Differences with BAD 3SA Mutant

Project description:The identification of genes driving organ development is central to understanding which signaling pathways drive the pathogenesis of various diseases including cancer. This dataset depicts the proteomic changes observed in C57BL/6J mice expressing wild-type or 3SA-phospho mutant versions of the Bcl-2-associated death promoter, BAD. This data shows that BAD regulates postnatal mammary gland morphogenesis in puberty. Three conserved serine residues on BAD are co-ordinately phosphorylated to regulate its activity. Non-phosphorylated BAD mutant delayed pubertal ductal elongation. This defect was specific to the epithelial compartment as transplant and ex vivo organoid assays of mutant epithelium recapitulated decreased tubule migration. Proteomic signature between BAD+/+ and phosphomutant BAD-3SA mammary glands identified differences in actin-binding and focal adhesion components. Mechanistically, non-phosphorylated BAD impedes protein translation, specifically in protrusions, through aberrant hypophosphorylated 4E-BP1. These findings reveal a critical enhancement of localized translation for efficient pubertal-mammary-gland morphogenesis and identifies BAD as a novel regulator of this process.

2021-03-29 | PXD014347 | Pride

miR205 Regulates Mammary Gland Development and Stem Cell Self-renewal through YAP and Wnt signaling

Project description:Mammary gland development is fueled by stem cell self-renewal and differentiation. External cues from the microenvironment coupled with internal cues such as post-transcriptional regulation exerted by miRNAs regulate stem cell behavior and stem cell fate. We have identified a miR205 regulatory network required for mammary gland morphogenesis and stem cell maintenance. In the postnatal mammary gland, miR205 is predominantly expressed in the basal/stem cell enriched population. Conditional deletion of miR205 in mammary epithelial cells severely impaired stem cell self-renewal and mammary repopulating potential both in vitro and in vivo. miR205 null glands displayed significant changes in the basal population, basement membrane and stroma. NKD1 and PP2A-B56, which inhibit the Wnt signaling pathway, and AMOT, which causes YAP cytoplasmic retention and inactivation were identified as miR205 downstream effectors. Collectively these findings reveal an essential role of miR205 in mammary gland development.

2018-12-27 | GSE124364 | GEO

RNA-sequencing of control and DMBA-treated WT and Cip2a-/- mouse mammary glands

Project description:The purpose is to study DMBA-induced transcriptome in WT and in Cip2a-/- mouse mammary gland tissues. We identified differentially expressed genes in DMBA-induced mammary gland in WT vs. Cip2a-/- mouse mammary glands.

2021-04-28 | GSE173405 | GEO

Gene expression of RonTK-/- mammary glands compared to RonTK+/+ controls during development

Project description:RON WT and RON KO at 5, 6, 7 week virgin mammary glands In the study, we demonstrated that RON regulates mammary gland branching morphogenesis in pubertal development associated with changes in gene expression. Keywords: Pubertal mammary glands

2009-06-16 | GSE16629 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data