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Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation [luminal cells]

ABSTRACT: Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation [luminal cells]

PROVIDER: PRJNA547672 | ENA |

REPOSITORIES: ENA

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Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation [luminal cells]

Project description:Integrin dimers α3/β1, α6/β1 and α6/β4 are the mammary epithelial cell receptors for laminins, which are major components of the basement membrane, a specialized extracellular matrix surrounding the mammary epithelium. The roles of specific basement membrane components and their integrin receptors in the regulation of functional gland development have not been analyzed in detail. To investigate the functions of laminin-binding integrins, we obtained mutant mice with mammary luminal cell-specific deficiencies of the α3 and α6 integrin chains generated by the Cre-Lox approach. During pregnancy, mutant mice displayed low levels of luminal progenitor activity and retarded lobulo-alveolar development, whereas their mammary glands seemed to be functional at the onset of lactation. Myoepithelial cell morphology was markedly altered in mutant glands, suggesting cellular compensation mechanisms involving cytoskeleton reorganization. However, lactation was not sustained in mutant mice, and the glands underwent precocious involution. Inactivation of the p53 gene rescued the growth defects but did not restore lactogenesis in mutant mice. This study reveals an essential role for laminin-binding integrins in functional mammary gland development.

2020-02-04 | GSE132349 | GEO

Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation

2020-02-04 | GSE132281 | GEO

Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation

Project description:Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation

| PRJNA547508 | ENA

Deciphering the mammary stem cell niche: a role for laminin-binding integrins

Project description:Integrin dimers a3/b1, a6/b1 and a6/b4 are the receptors of mammary epithelial cells for Laminin, major component of the mammary basement membrane. Antibodies against a6 and a3 integrin chains serve to isolate stem cell enriched populations from mammary epithelium, however, role of integrin dimers comprising these chains in the control of mammary stem cell activity are not known. To investigate the role of Laminin-binding integrins in the control of mammary stem cell function, a3 and a6 chains were deleted from mammary basal cells in vitro using Cre-recombinase carrying adenovirus. We found that deletion of single integrin chain (either a3, or a6) did not significantly affect stem cell potential as evaluated by transplantation and mammosphere assays, whereas basal cells depleted of both a3 and a6 integrin chains (a3a6KO) presented severely diminished stem cell activity. In this study the transcriptional profiles of a3a6KO were analysed and compared to those of control cells.

2019-04-23 | GSE117120 | GEO

Deciphering the mammary stem cell niche: a role for laminin-binding integrins

Project description:Deciphering the mammary stem cell niche: a role for laminin-binding integrins

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The uterine secretory cycle: recurring physiology of endometrial outputs that setup the uterine luminal microenvironment

Project description:The bovine endometrium secretes proteins across the estrous cycle that vary (in both protein identity and abundance) to be in synchrony with luminal reproductive events. To uncover the identity of these proteins, transcriptomics was performed to understand the secretory capability of the bovine endometrium through the distinct phases of the estrous cycle in cows. This dataset should serve as a baseline for understanding the profile of luminal secretory outputs across the estrous cycle, setting the stage for functional interpretation of how the uterus supports and directs biological events ranging from sperm transport to preimplantation embryo development.

2023-03-20 | GSE180279 | GEO

Effect of laminin adhesion on basal human mammary epithelial cells

Project description:Mammary epithelium is composed by luminal and basal epithelial cells, which are adhere to the basement membrane (BM). To dissect how basal cell functions are regulated by BM laminin adhesion, we performed RNA sequencing of basal human mammary epithelial cells adhered on laminin-111, -421 or -521 coated cell culture plates for 48 hours.

2022-11-07 | GSE197950 | GEO

Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk

Project description:Breast cancer risk is influenced by parity in an age-dependant manner, however human tissue remodelling induced by pregnancy and lactation is not well understood. In most cases, it is difficult to acquire human breast tissue during these key stages of development. Here, we present an approach to overcome this using single-cell RNA sequencing to examine viable primary mammary epithelial cells isolated from human milk (n=5, LMC) compared to resting, non-lactating human breast tissue (n=3, NMC). We identified all documented mammary subpopulations within our breast tissue samples and found that milk contains distinct secretory luminal cells together with myeloid and lymphocytic lineage cells. Comparing the luminal transcriptional profiles of cells isolated from the resting and lactating state identified differences in mammary cell function and metabolism between these maturation states. This data may be used to provide an insight into how parity influences human luminal cell metabolism and breast cancer risk.

2021-12-10 | E-MTAB-10855 | biostudies-arrayexpress

Combination scaffolds of salmon fibrin, hyaluronic acid, and laminin for human neural stem cell tissue engineering

Project description:A goal of this project is to evaluate the integrin mRNA expression in human neural stem/progenitor cells (hNSPC) using high-throughput sequencing technologies. We found high levels of mRNA expression for the β1, α7, α3, α6, β5, αV, α5, and α9 integrins. This suggests that hNSPCs may express integrin receptors that can bind fibrinogen and laminin proteins.

2016-12-14 | GSE76011 | GEO

Idiosyncratic nature of lactation reveals link to breast cancer risk.

Project description:Breastfeeding protects against breast cancer in some women but not others, however the mechanism remains elusive. Lactation requires intense secretory activity of the endoplasmic reticulum (ER) for the production of milk proteins and ER- mitochondria contacts for lipid synthesis. We show that in female mice that share the same nuclear genome (BL/6) but differ in mitochondrial genomes (C57 or NZB), the biological processes engaged during lactation are entirely different at the sub-cellular organization and transcriptional levels resulting in anti-tumorigenic lactation in BL/6C57 females and pro-tumorigenic lactation in BL/6NZB females. Single cell sequencing identified a sub-population of cells, uniquely amplified during lactation in BL/6NZB females, which shares the genetic signature that characterizes post-partum breast cancer (PPBC) in humans relative to matched breast cancers in never pregnant women. Our data indicate that differences in ER and mitochondrial-stress responses during lactation between genotypes inadvertently leads to loss of p53 tumor suppressor function in BL/6NZB females allowing the expansion of the PPBC-like sub-population of cells. Overall, our data reveals the unexpected idiosyncratic nature of lactation and its impacts on the risk of the development of PPBC.

2025-05-28 | GSE272354 | GEO

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