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FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age

ABSTRACT: FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age

PROVIDER: PRJNA661758 | ENA |

REPOSITORIES: ENA

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FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age (RNA-seq)

Project description:We identify two quiescent stem-cell states through relative CD34 expression: CD34High, with stemness properties (genuine state), and CD34Low, more committed to myogenic differentiation (primed state). The genuine-quiescent state is preserved into later life succumbing only in extreme old age due to acquisition of primed-state traits. We identified niche-derived IGF1-dependent Akt activation as detrimental to the genuine stem-cell state by imposing primed-state features via FoxO inhibition. Interventions to neutralize Akt and promote FoxO activity drive primed-to-genuine state conversion, while FoxO inactivation deteriorates the genuine state at young age, causing muscle regenerative failure, as in geriatric mice.

2020-10-29 | GSE157562 | GEO

FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age (ATAC-seq)

2020-10-29 | GSE155642 | GEO

FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age (RNA-seq)

Project description:FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age (RNA-seq)

| PRJNA661759 | ENA

FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age (ATAC-seq)

Project description:FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age (ATAC-seq)

| PRJNA650532 | ENA

FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-10-29 | GSE157563 | GEO

Endothelial ERK1/2 signaling maintains integrity of the quiescent endothelium

Project description:Endothelial ERK1/2 signaling maintains integrity of the quiescent endothelium

| PRJNA541240 | ENA

Mitochondrial respiration maintains autophagy to support stress resistance in quiescent cells

Project description:Mitochondrial respiration maintains autophagy to support stress resistance in quiescent cells

| PRJNA609070 | ENA

Titered FOXO overexpression maintains cardiac proteostasis and ameliorates age-associated functional decline

Project description:Heart performance declines with age. Reduced protein quality control (PQC) due to decreased function of the ubiquitin/proteasome system (UPS), autophagy, and/or chaperone-mediated protein refolding is a likely contributor to age-associated cardiac performance decline. The transcription factor FOXO participates in the regulation of genes involved PQC and a host of other processes. Here, the effect of cardiac-restricted dFOXO overexpression was investigated in Drosophila, a genetically pliable and rapidly aging model. Modest dFOXO overexpression in the heart was protective, ameliorating functional decline with age. Increased expression of genes associated predominantly with UPS relative to other PQC components accompanied dFOXO-mediated cardioprotection, which was corroborated by a significant decrease in ubiquitinated myocardial proteins. In agreement, knockdown of upregulated UPS components seemingly induced premature aging. Despite these findings, excessive dFOXO overexpression or knockdown proved detrimental to heart function and overall organismal development. This study highlights Drosophila as a model of cardiac aging and FOXO as a tightly-regulated mediator of proteostasis and heart performance over time. Two replicates of 4 different samples were analyzed. Two of these samples were controls (GMH5 x yw 1 week and GMH5 x yw 5 week).

2016-07-01 | E-GEOD-73205 | biostudies-arrayexpress

DK010: FOXO target gene CTDSP2 inhibits cell cycle progression through regulation of p21-Cip1/Waf1

Project description:Activity of Forkhead box O (FOXO) transcription factors is inhibited by PI3K-PKB/Akt signalling to control a variety of cellular processes including cell cycle progression. Through comparative analysis of a number of microarray datasets, we identified a set of genes commonly regulated by FOXO and PI3K/PKB, which includes Carboxyl-Terminal Domain Small Phosphatase 2 (CTDSP2). We validated CTDSP2 as a genuine FOXO target gene and show that ectopic CTDSP2 can induce cell cycle arrest. We analysed transcriptional regulation after CTDSP2 expression and identified extensive regulation of genes involved in cell cycle progression, which depends on the phosphatase activity of CTDSP2. Most notably regulated genes are p21Cip1/Waf1 and E2F1, both implicated in S-phase entry. We show that p21Cip1/Waf1 is regulated by CTDSP2 in a p53-independent manner and that p21Cip1/Waf1 upregulation results in decreased cyclin/CDK2 and cyclin/CDK6 activity. Thus, we identify FOXO-dependent CTDSP2 regulation as a novel regulatory mechanism for inhibiting proliferation in the absence of growth factor/PI3K signalling.

2015-05-29 | GSE58986 | GEO

DK009: FOXO target gene CTDSP2 inhibits cell cycle progression through regulation of p21-Cip1/Waf1

2015-05-29 | GSE58947 | GEO

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