mTORC1 controls the systemically-induced adaptive regulation of stem cell quiescence into GAlert
Transcriptomics Dataset
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General Information
AccessionGSE55490
TitlemTORC1 controls the systemically-induced adaptive regulation of stem cell quiescence into GAlert
DescriptionA unique property of many adult stem cells is their ability to exist in a non-cycling, quiescent state. Although quiescence serves an essential role in preserving stem cell function until the stem cell is needed in tissue homeostasis or repair, defects in quiescence can lead to an impairment in tissue function, the extent to which stem cells can regulate quiescence is unknown. Here, we show that the stem cell quiescent state is composed of two distinct functional phases: G0 and an alert phase we term GAlert, and that stem cells actively and reversibly transition between these phases in response to injury-induced, systemic signals. Using genetic models specific to muscle stem cells (or satellite cells (SCs)), we show that mTORC1 activity is necessary and sufficient for the transition of SCs from G0 into GAlert and that signaling through the HGF receptor, cMet is also necessary. We also identify G0-to-GAlert transitions in several populations of quiescent stem cells. Quiescent stem cells that transition into GAlert possess enhanced tissue regenerative function. We propose that the transition of quiescent stem cells into GAlert functions as an 'alerting' mechanism, a novel adaptive response that positions stem cells to respond rapidly under conditions of injury and stress without requiring cell cycle entry or a cell fate commitment. We performed microarray analysis on muscle stem cells, harvested immediately after isolation, to investigate the transcriptional response these cells have to injury and the role of mTORC1 and cMet have in this response
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55490
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
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Dataset Accession
Tool Name
Direction
Hs Gene Symbol
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Geneset
Small molecules which mimic TSC1 KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse TSC1 KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic RPTOR KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse RPTOR KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic MET KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse MET KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in TSC1 KO
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes dysregulated in RPTOR KO
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes dysregulated in MET KO
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in TSC1 KO
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
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