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Title: Notch targets stem-cell and temporal-programming genes to orchestrate neuroblast tumours      
dateReleased:
10-18-2016
description:
Notch signalling is involved in a multitude of developmental decisions and its aberrant activation is linked to many diseases, including cancers. One such example is the neural stem cell tumours that arise from constitutive Notch activity in Drosophila neuroblasts. To investigate how hyper-activation of Notch in larval neuroblasts leads to tumours, we combined results from profiling the upregulated mRNAs and mapping the regions bound by Su(H) (the core Notch pathway transcription factor ). This identified 127 putative direct Notch targets that were up-regulated in the hyperplastic tissue. These genes were highly enriched for transcription factors (TFs) and overlapped significantly with a previously identified regulatory programme dependent on the proneural transcription factor Asense. Included were genes associated with the neuroblast maintenance and self-renewal programme that we validated as Notch regulated in vivo. A second category contained so-called temporal transcription factors, which are involved in neuroblast progression. Normally expressed in specific time windows, several temporal transcription factors were ectopically expressed in the stem cell tumours, suggesting that Notch had reprogrammed the normal temporal hierarchy. Indeed, the Notch-induced hyperplasia was reduced by mutations affecting two of the temporal factors which, conversely, were sufficient to induce mild hyperplasia on their own. Altogether the results demonstrate that Notch induces neural stem cell tumors by promoting the expression of genes that contribute to stem cell identity and by reprogramming expression of temporal factors that regulate maturity.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-MTAB-3561
refinement:
raw
dateSubmitted:
11-12-2013
keywords:
functional genomics
dateModified:
10-18-2016
creators:
George Garinis A.
availability:
available
types:
gene expression
name:
Drosophila melanogaster
name:
genetic modification design
ID:
A-AFFY-35
name:
Affymetrix GeneChip Drosophila Genome 2.0 Array [Drosophila_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-3561/E-MTAB-3561.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-MTAB-3561/E-MTAB-3561.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
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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