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Series GSE44561 Query DataSets for GSE44561
Status Public on Jun 04, 2014
Title Effect of Notch1 pathway activation on high-grade glioma cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary In this study, we explored the transcriptomic consequences of strong activation of the Notch pathway in embryonic human neural stem cells and in gliomas. For this we used a forced expression of the Notch intracellular domain (NICD).

Glioblastoma multiforms (GBMs) are highly vascularized brain tumors containing a subpopulation of multipotent cancer stem cells. These cells closely interact with endothelial cells in neurovascular niches. In this study we have uncovered a close link between the Notch1 pathway and the tumoral vascularization process of GBM stem cells. We observed that although the Notch1 receptor was activated, the typical target proteins (HES5, HEY1, HEY2) were not or barely expressed in two explored GBM stem cell cultures. Notch1 signalling activation by expression of the intracellular form (NICD) in these cells was found to reduce their growth rate and migration which was accompanied by the sharp reduction of neural stem cell transcription factor expression (ASCL1, OLIG2, SOX2) while HEY1/2, KLF9, SNAI2 transcription factors were upregulated. Expression of OLIG2 and growth were restored after termination of Notch1 stimulation. Remarkably, NICD expression induced the expression of pericyte cell markers (NG2, PDGFRb and a-smooth muscle actin (aSMA)) in GBM stem cells. This was paralleled with the induction of several angiogenesis-related factors most notably cytokines (HB-EGF, IL8, PLGF), metalloprotease (MMP9) and adhesion proteins (VCAM-1, ICAM-1, ITGA9). In xenotransplantation experiments, contrasting with the infiltrative and poorly-vascularized tumors obtained with control GBM stem cells, Notch1 stimulation resulted in poorly-disseminating but highly-vascularized grafts containing large vessels with lumen. Notch1-stimulated GBM cells expressed pericyte cell markers and closely associated with endothelial cells. These results reveal an important role for the Notch1 pathway in regulating GBM stem cell plasticity and angiogenic properties.
 
Overall design Embryonic human neural progenitors obtained from Lonza, the U87 glioma cell line, and glioma cancer stem cells (Gb4 and Gb7) characterized in Guichet et al. (Glia, 2013, 61(2), 225-39) were infected with lentiviruses expressing YFP or YFP-IRES-NICD (activated form of Notch receptor). After 48h, RNA were extracted for Affymetrix microarray analysis.
 
Contributor(s) Hugnot JP, Guichet PO, Rothhut B
Citation(s) 24898819
Submission date Feb 21, 2013
Last update date Nov 08, 2016
Contact name jean philippe hugnot
E-mail(s) hugnot@gmail.com
Organization name inserm inm u1051
Lab stem cells
Street address hopital saint eloi 80 avenue augustin fliche
City montpellier
State/province languedoc
ZIP/Postal code 34091
Country France
 
Platforms (1)
GPL11532 [HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version]
Samples (8)
GSM1086967 Human neural stem cell infected with YFP lentivirus
GSM1086968 Human neural stem cell infected with YFP-NICD lentivirus
GSM1086969 U87 cell line infected with YFP lentivirus
Relations
BioProject PRJNA190058

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE44561_RAW.tar 36.8 Mb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file

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