Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Aberrant activation of p53/p66Shc-mInsc axis increases asymmetric divisions and attenuates proliferation of aged mammary stem cells.

ABSTRACT: Mammary gland aging is due to aberrant activation of p66Shc, which induces p53/p44 signaling, leading to failure of symmetric divisions, decreased proliferation and reduced regenerative potential of MaSCs. Age-related changes in mammary epithelial cells derived from C57BL/6J WT and p66Shc knockedout mice cultured as stem cell-enriched mammospheres.

ORGANISM(S): Mus musculus

PROVIDER: GSE201253 | GEO | 2022/12/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Aberrant activation of p53/p66Shc-mInsc axis increases asymmetric divisions and attenuates proliferation of aged mammary stem cells.

Project description:Aberrant activation of p53/p66Shc-mInsc axis increases asymmetric divisions and attenuates proliferation of aged mammary stem cells.

| PRJNA830505 | ENA

Asymmetric Segregation of the Nucleosome Remodeling and Deacetylase Complex during Asymmetric Cell Divisions

Project description:Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates. Epigenetic mechanisms are crucial for cell fate specification, and it remains unclear how epigenetic information is inherited. Here, we report asymmetric segregation of the nucleosome remodeling and deacetylase complex (NuRD) during ACDs in Caenorhabditis elegans. NuRD is enriched to chromosomes of the future surviving but not apoptotic daughter cell, whereas NuRD evenly distributes to two viable siblings. Disruption of ACDs causes symmetric NuRD inheritance, and an ectopic gain of NuRD in apoptotic daughters allows cell survival and differentiation. Lack of NuRD upregulates the expression of the vital cell death-inducing gene egl-1 by increasing H3K27 acetylation on the egl-1 locus, which activates the EGL-1-CED-9-CED-4-CED-3 pathway to promote apoptosis. We propose that biased NuRD segregation during ACDs provides a previously unrecognized yet common mechanism for asymmetrically partitioning epigenetic information that contributes to binary cell fate decisions.

2022-12-30 | GSE167379 | GEO

Identification of p66Shc promoter interactional DNA fragments using Circularized Chromosome Conformation Capture coupled with next-generation sequencing (4C-seq)

Project description:p66Shc is encoded by the SHC1 gene, which contains two tandem promoters that generate three proteins (p46, p52 and p66). More recently, p66Shc was found to localize to focal adhesions that reports cell attachment and is required for anoikis through a RhoA-dependent mechanosensory test (Ma et al., J Cell Biol, 179, 23-31). Consistent with its role in anoikis, p66Shc is expressed in normal epithelial and endothelial cells but not in hematopoietic cells that survive in unanchored conditions. To uncover the epigenetic regulation mechanisms of p66Shc expression, here we performed 4C-seq assays with p66Shc promoter as a bait in HUVEC and U937 cells. Our results identify different p66Shc promoter interactional DNA fragments in different cell types.

2017-12-30 | GSE106449 | GEO

Regulation of cellular heterogeneity and rates of symmetric and asymmetric divisions in triple-negative breast cancer

Project description:Regulation of cellular heterogeneity and rates of symmetric and asymmetric divisions in triple-negative breast cancer

| PRJNA328149 | ENA

NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling

Project description:NAD+ levels decline with age and in certain disease conditions. NAD+ precursors have been shown to stimulate NAD+ biosynthesis and ameliorate various age-associated diseases in mouse models. However, NAD+ metabolism is complicated in cancer and its role in triple-negative breast cancer (TNBC) remains elusive. Here, we show that NAD+ supplement suppresses tumor metastasis in a TNBC orthotopic patient-derived xenograft (PDX) model. Sirtuin1 lysine deacetylase (SIRT1) is required for the effects since SIRT1 knockdown blocks NAD+-suppressed tumor metastasis. Overexpression of SIRT1 effectively impairs the metastatic potential of TNBC. Importantly, the interaction between SIRT1 and p66Shc causes the deacetylation and functional inactivation of p66Shc, which inhibits epithelial-mesenchymal transition (EMT). Overall, we demonstrate that NAD+ supplementation executes its anti-tumor function via activating the SIRT1-p66Shc axis, which highlights the preventive and therapeutic potential of SIRT1 activators as effective interventions for TNBC.

2023-01-23 | GSE220683 | GEO

Asymmetric Segregation of the Nucleosome Remodeling and Deacetylase Complex during Asymmetric Cell Divisions

Project description:Asymmetric Segregation of the Nucleosome Remodeling and Deacetylase Complex during Asymmetric Cell Divisions

| PRJNA704418 | ENA

Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles

Project description:Aging organs functionally and structurally decline with the loss of their regenerative capabilities, yet the existence of distinct cell division programs that determine organ fates is unknown. Hair follicles, mammalian mini-organs that grow hair, miniaturize by aging. Here we report that hair follicle regeneration and aging are driven by distinct cell division types of hair follicle stem cells (HFSCs). Cell fate tracing and cell division axis analysis in mice revealed that HFSCs undergo symmetric and asymmetric cell divisions to generate a new bulge, yet preferentially provoke “stress-responsive type” asymmetric cell divisions that generate aberrantly differentiating cells upon age/stress. That dynamic program with repetitive divisions efficiently eradicates those cells through defective association and stabilization of a hemidesmosomal protein COL17A1 and a cell-polarity-protein aPKCλ in HFSCs, thereby causing organ aging. The forced stabilization of COL17A1 rescued organ aging through aPKCλ stabilization. These results demonstrate that distinct cell division programs govern tissue/organ fates.

2020-12-25 | GSE124119 | GEO

Identification of long-lived proteins retained in cells undergoing repeated asymmetric divisions

Project description:To identify long-lived proteins that are retained in yeast mother cells, we combined a method developed in our lab with a pulse-chase protocol using total proteome analysis. Cells were initially grown in medium with stable heavy-isotope amino acids to label proteins. The cells were then switched into media containing light-isotope amino acids and cultured for an additional ~18 cell divisions with the MEP engaged. Finally, we determined whether any of the original heavy-labeled proteins were still present in the aged mother cells

2014-09-01 | PXD001251 | Pride

Regulators of cellular heterogeneity in basal-like breast cancer influence symmetric versus asymmetric division rates (shRNA targeting)

Project description:Differentiation events contribute to cellular heterogeneity within tumors and influence disease progression and response to therapy. Here we dissect the mechanisms controlling intratumoral heterogeneity within basal-like breast cancers. We show that cancer cells can transition between a differentiation state related to that of normal luminal progenitors and a state closer to that of mature luminal cells, and that this occurs through asymmetric cell divisions. The Polycomb factor EZH2 and the Notch pathway act to increase the rates of symmetric divisions that produce progenitor-like cells, while the FOXA1 transcription factor promotes asymmetric divisions that reduce the numbers of such cells. Through functional screening, we identified a group of regulators that control cancer cell differentiation state and the relative proportions of tumor cell subpopulations. Our findings highlight the regulation of asymmetric cell divisions as a mechanism controlling intratumoral heterogeneity, and identify molecular pathways that control breast cancer cellular composition.

2018-08-26 | GSE84143 | GEO

Regulators of cellular heterogeneity in basal-like breast cancer influence symmetric versus asymmetric division rates (Expression profiles)

2018-08-26 | GSE84080 | GEO