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Title: Genome-wide analysis reveals conserved transcriptional responses downstream of resting potential change in Xenopus embryos, axolotl regeneration, and human mesenchymal cell differentiation [frog data]      
dateReleased:
07-03-2016
description:
Endogenous bioelectric signaling via changes in cellular resting potential (Vmem) is a key regulator of patterning during regeneration and embryogenesis in numerous model systems. Depolarization of Vmem has been functionally implicated in de-differentiation, tumorigenesis, anatomical re-specification, and appendage regeneration. However, no unbiased analyses have been performed to understand genome-wide transcriptional responses to Vmem change in vivo. Moreover, it is unknown which genes or gene networks represent conserved targets of bioelectrical signaling across different patterning contexts and species. Here, we use microarray analysis to comparatively analyze transcriptional responses to specific Vmem depolarization. We compare the response of the transcriptome during embryogenesis (Xenopus development), regeneration (Axolotl regeneration), and stem cell differentiation (human mesenchymal stem cells in culture) to identify common networks across model species that are associated with depolarization. Both sub-network enrichment and PANTHER analyses identified a number of key genetic modules as targets of Vmem change, and also revealed important (well-conserved) commonalities in bioelectric signal transduction, despite highly diverse experimental contexts and species. Depolarization regulates specific transcriptional networks across all three germ layers (ectoderm, mesoderm and endoderm) such as cell differentiation and apoptosis, and this information will be used for developing mechanistic models of bioelectric regulation of patterning. Moreover, our analysis reveals that Vmem change regulates transcripts related to important disease pathways such as cancer and neurodegeneration, which may represent novel targets for emerging electroceutical therapies. Xenopus laevis embryos were fertilized in vitro according to standard protocols (Sive 2000) in 0.1X Marc’s Modified Ringer’s (MMR; 10mM Na+, 0.2mM K+,10.5mM Cl, 0.2 mM Ca2+, pH 7.8). Intracellular ion concentrations in Xenopus embryo are: 21mM Na+, 90mM K+, 60mM Cl-, 0.5mM Ca2+ (Gillespie 1983). Xenopus embryos were housed at 14-18oC and staged according to Nieuwkoop and Faber (Nieuwkoop 1967). All experiments were approved by the Tufts University Animal Research Committee (M2014-79) in accordance with the guide for care and use of laboratory animals. Capped synthetic mRNAs generated using mMessage mMachine kit (Ambion) were dissolved in nuclease free water and injected into the embryos in 3% Ficoll using standard methods (Sive 2000). Each injection delivered between 1-2 nL or 1– 2 ng of mRNA (per blastomere) into the embryos, usually at 4-cell stage into the middle of the cell in the animal pole. Constructs used were: GlyR (Davies et al. 2003) and 666 chimera (Hough et al. 2000).
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-72097
refinement:
raw
alternateIdentifiers:
72097
keywords:
functional genomics
dateModified:
12-28-2016
availability:
available
types:
gene expression
name:
Xenopus laevis
ID:
A-GEOD-10756
name:
[X_laevis_2] Affymetrix Xenopus laevis Genome 2.0 Array
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-72097/E-GEOD-72097.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-72097/E-GEOD-72097.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72097
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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