Dataset Information

Expression profiling after ICAP1 or constitutive active NOTCH1 over expression in human umbilical vein endothelial cells

ABSTRACT: ICAP1 (also known as ITG1BP1) is a protein interaction partner of beta1-integrins and the cerebral cavernous malformation protein 1 (CCM1, also known as KRIT1). In mice Icap1 plays an important role for bone development. The function of ICAP1 in endothelial cells is poorly understood. However, the interactions with beta1-integrins and CCM1 suggest that ICAP1 should play an important role also in endothelial cells. We obtained data that ICAP1 might activate the Delta-Notch signaling cascade, a critical regulator of endothelial proliferation, migration and sprouting angiogenesis. This genome-wide expression analysis is aimed to unravelling novel mechanisms or signaling pathways how ICAP1 functions in endothelial cells. Secondly, this study aimed at defining novel target genes of Notch signaling and finally to compare the gene expression patterns of ICAP1 and NOTCH1. We used human umbilical vein endothelial cells (HUVEC) as a model system to study ICAP1 and NOTCH1 functions after adenoviral over expression in comparison to GFP over expression as control. The results of this experiment suggest that ICAP1 and NOTCH1 control a series of genes involved in cell proliferation, migration and angiogenesis. A high proportion of ICAP1-regulated genes is also regulated by NOTCH1 in a very similar manner.

ORGANISM(S): Homo sapiens

PROVIDER: GSE18035 | GEO | 2010/07/02

SECONDARY ACCESSION(S): PRJNA119889

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description: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. 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.

Dataset Information

Expression profiling after ICAP1 or constitutive active NOTCH1 over expression in human umbilical vein endothelial cells

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure