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Title: Global gene expression in response to genetic and growth factor manipulation of TWIST1 expression and function      
dateReleased:
12-19-2015
description:
In addition to their stem/progenitor properties, mesenchymal stem cells (MSCs) also exhibit various effector functions potent effector (angiogenic, anti-inflammatory, immune-modulatory) functions that are largely paracrine in nature. It is widely believed that effector functions underlie most of the therapeutic potential of MSCs and are independent of their stem/progenitor properties. Here we demonstrate that stem/progenitor and effector functions are coordinately regulated at the cellular level by the transcription factor Twist1 and specified within populations according to a hierarchical model. We further show that manipulation of Twist1 levels by genetic approaches or by exposure to widely used culture supplements including fibroblast growth factor 2 (Ffg2) and interferon gamma (IFN-gamma) alters MSC efficacy in cell-based and in vivo assays in a predictable manner. Thus, by mechanistically linking stem/progenitor and effector functions our studies provide a unifying framework in the form of an MSC hierarchy that models the functional complexity of populations. Using this framework, we developed a Clinical Indications Prediction (CLIP) scale that predicts how donor-to-donor heterogeneity and culture conditions impact the therapeutic efficacy of MSC populations for different disease indications. We used microarrays to detail the global gene expression in response to genetic and growth factor manipulation of TWIST1 expression and function. Mesenchymal stem cells at subconfluent culture in growth media (CONTROL), or supplemented with FGF2 (20 ng/ml) (FGF2), trasfected with scrambled (SCRAMBLED) or TWIST1 siRNA (TWIST1) were used for RNA extraction and hybridization on Affimentrix microarrays. We pooled three independently extracted RNA samples per group.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-76158
refinement:
raw
alternateIdentifiers:
76158
keywords:
functional genomics
dateModified:
12-27-2015
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-16686
name:
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-76158/E-GEOD-76158.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-76158/E-GEOD-76158.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=GSE76158
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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