{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "mouse", "factors": [{"GSM1371349": {"TRANSFECTION": "empty vector (pMYs-IRES-GFP)"}}, {"GSM1371350": {"TRANSFECTION": "retrovirus vector pMYs-Hes1-IRES-GFP"}}], "id": 7624, "ownerprofile_id": "arrayexpress_sid", "platform": 6, "summary_wrapped": "High levels of Hes1 expression are frequently found in BCR-ABL-positive chronic myelogenous leukemia in blast crisis (CML-BC). In mouse...", "geo_gse_id": "E-GEOD-56921", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 1, "sample_count": 2, "tags": ["bone", "bone marrow", "cell", "chronic myelogenous leukemia", "disease", "genome", "leukemia", "plat", "serum", "stromal cell"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_id_plat": "E-GEOD-56921_A-AFFY-45", "slug": "expression-analysis-of-common-myeloid-progenitors", "geo_gds_id": "", "name": "Expression analysis of common myeloid progenitors (CMPs) expressing Hes1", "created": "Nov.12, 2014", "summary": "High levels of Hes1 expression are frequently found in BCR-ABL-positive chronic myelogenous leukemia in blast crisis (CML-BC). In mouse bone marrow transplantation (BMT) models, co-expression of BCR-ABL and Hes1 induces CML-BC\u2013like disease; however the underlying mechanism remained elusive. Here, based on gene expression analysis, we show that MMP-9 is upregulated by Hes1 in common myeloid progenitors (CMPs). Analysis of promoter activity demonstrated that Hes1 upregulated MMP-9 by activating NF-kB. Analysis of 20 samples from CML-BC patients showed that MMP-9 was highly expressed in three, with two exhibiting high levels of Hes1 expression. Interestingly, MMP-9 deficiency impaired the cobblestone area-forming ability of CMPs expressing BCR-ABL and Hes1 that were in conjunction with a stromal cell layer. In addition, these CMPs secreted MMP-9, promoting the release of soluble Kit-ligand (sKitL) from stromal cells, thereby enhancing proliferation of the leukemic cells. In accordance, mice transplanted with CMPs expressing BCR-ABL and Hes1 exhibited high levels of sKitL as well as MMP-9 in the serum. Importantly, MMP-9 deficiency impaired the development of CML-BC\u2013like disease induced by BCR-ABL and Hes1 in mouse BMT models. The present results suggest that Hes1 promotes the development of CML-BC, partly through MMP-9 upregulation in leukemic cells. Common myeloid progenitors (CMPs; Lineage negative, c-Kit positive, Sca-1 negative, Fc-gamma-receptor low, CD34 positive fraction) were sorted with a FACSAria cell sorter (Becton Dickinson). Retroviruses were generated by transfecting Plat-E packaging cells with retrovirus vector pMYs-Hes1-IRES-GFP or empty vector (pMYs-IRES-GFP) using FuGENE 6 (Roche Diagnostics). Infection of retrovirus harboring Hes1 (pMYs-Hes1-IRES-GFP) or empty vector (pMYs-IRES-GFP) into progenitors was performed using RetroNectin (Takara Bio).  Hes1-transfected CMPs and Mock-transduced CMPs were isolated 36 hours after infection with a FACSAria cell sorter. One sample of Hes1-transfected CMPs and one sample of mock-transduced CMPs were analyzed with GeneChip Mouse Genome 430 2.0 Array.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-56921", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-56921/samples/"}