Expression data from epidermal stem cells isolated from dorsal skin of P19 Per1-Venus mice and Bmal1 epidermal knockout mice
Transcriptomics Dataset
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General Information
AccessionGSE27079
TitleExpression data from epidermal stem cells isolated from dorsal skin of P19 Per1-Venus mice and Bmal1 epidermal knockout mice
DescriptionEpidermal stem cells ensure that skin homeostasis is maintained. In murine skin, epidermal stem cells cluster at specific niches where, under steady-state conditions, they undergo cycles of dormancy and activation1. When cellular replenishment is required, epidermal stem cells egress from the niche and proliferate for a limited number of times to subsequently feed into the differentiated compartment1-3. However, only a subset of stem cells becomes active during each round of morphogenesis, suggesting that stem cells coexist in heterogeneous responsive states within the same niche. Using a circadian clock fluorescent reporter mouse model, we show that the dormant epidermal stem cell niche contains two coexisting populations of stem cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. In dormant niches, the core molecular clock protein Bmal1 transcriptionally modulates the expression of stem cell regulatory genes, including modulators of Wnt and TGFb, to create two coexisting stem cell populations, one predisposed, and the other less prone, to activation. Unbalancing this equilibrium of epidermal stem cells, through conditional epidermal deletion of Bmal1, resulted in a long-term progressive accumulation of non-responsive stem cells, premature impairment of tissue self-renewal, and a significant reduction in the development of squamous cell carcinomas. Our results indicate that the molecular clock machinery fine-tunes the spatiotemporal behavior of epidermal stem cells within their niche, and that perturbation of this mechanism affects tissue homeostasis and the predisposition to neoplastic transformation. The goals of this study was to compare the transcriptome of epidermal stem cells according to their circadian rhythm phase. We isolated epidermal stem cells (bulge cells; alpha6bright/CD34+ population) from 19 days old Per1-Venus mice and separated them according to Venusbright (clock positive) and Venus dim (clock negative). The goals of this study was to compare the transcriptome of epidermal stem cells in which their circadian rhythm machinery has been perturbed by deleting the gene that encodes for Bmal1. We compared the transcriptomes of basal interfollicular epidermis cells (alpha6 integrin bright/CD34- cells) from the dorsal skin of 1 year old BmalKO mice and their respective control littermates. Each array corresponds to purified cells from approximately 5 mice.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27079
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

Dataset Accession
Tool Name
Direction
Geneset

Small molecules which mimic ARNTL KO
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Small molecules which reverse ARNTL KO
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in ARNTL KO
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in ARNTL KO
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in ARNTL KO
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Enrichment analysis of genes downregulated in ARNTL KO
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in ARNTL KO
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
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