{"owner": "ArrayExpress Uploader", "pop_total": 0, "id": 4764, "factors": [{"GSE5827GSM132932": {}}, {"GSE5827GSM132933": {}}, {"GSE5827GSM132964": {}}, {"GSE5827GSM132965": {}}, {"GSE5827GSM132934": {}}, {"GSE5827GSM132935": {}}, {"GSE5827GSM132966": {}}, {"GSE5827GSM132988": {}}, {"GSE5827GSM132936": {}}, {"GSE5827GSM132937": {}}, {"GSE5827GSM132991": {}}, {"GSE5827GSM132994": {}}, {"GSE5827GSM132939": {}}, {"GSE5827GSM132940": {}}, {"GSE5827GSM133004": {}}, {"GSE5827GSM133006": {}}, {"GSE5827GSM132942": {}}, {"GSE5827GSM132943": {}}, {"GSE5827GSM133023": {}}, {"GSE5827GSM133007": {}}, {"GSE5827GSM132945": {}}, {"GSE5827GSM132946": {}}, {"GSE5827GSM133010": {}}, {"GSE5827GSM133011": {}}, {"GSE5827GSM132962": {}}, {"GSE5827GSM132963": {}}, {"GSE5827GSM133020": {}}, {"GSE5827GSM133021": {}}], "ownerprofile_id": "arrayexpress_sid", "platform": 4, "summary_wrapped": "The NOTCH1 signaling pathway directly links extracellular signals with transcriptional responses in the cell nucleus and plays a critical...", "pubmed_id": 17114293, "geo_gse_id": "E-GEOD-5827", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 0, "sample_count": 28, "tags": ["cell", "cell nucleus", "leukemia", "lymphoblastic leukemia"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "transcription-profiling-of-human-t-all-cell-cultur", "geo_id_plat": "E-GEOD-5827_A-AFFY-44", "name": "Transcription profiling of human T-ALL cell cultures treated with Compound E, a gamma-secretase inhibitor or vehicle only (DMSO) for 24 h", "created": "Sep.21, 2014", "summary": "The NOTCH1 signaling pathway directly links extracellular signals with transcriptional responses in the cell nucleus and plays a critical role during T-cell development and in the pathogenesis over 50% of human T-cell lymphoblastic leukemia (T-ALL) cases. However, little is known about the transcriptional programs activated by NOTCH1. Using an integrative systems biology approach we show that NOTCH1 controls a feed-forward loop transcriptional network that promotes cell growth. Inhibition of NOTCH1 signaling in T-ALL cells led to a reduction in cell size and elicited a gene expression signature dominated by downregulated biosynthetic pathway genes. By integrating gene expression array and ChIP-on-chip data, we show that NOTCH1 directly activates multiple biosynthetic routes and induces c-MYC gene expression. Reverse engineering of regulatory networks from expression profiles showed that NOTCH1 and c-MYC govern two directly interconnected transcriptional programs containing common target genes that together regulate the growth of primary T-ALL cells. These results identify c-MYC as an essential mediator of NOTCH1 signaling and integrate NOTCH1 activation with oncogenic signaling pathways upstream of c-MYC. Experiment Overall Design: Duplicated cultures of T-ALL cell lines were treated with Compound E, a gamma-secretase inhibitor or vehicle only (DMSO) for 24 h and analyzed using oligonucleotide microarrays. Gene expression changes were analyzed in the context of loss of NOTCH1 signaling induced by the gamma secretase inhibitor treatment.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-5827", "species": "human", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-5827/samples/"}