{"owner": "ArrayExpress Uploader", "ownerprofile_id": "arrayexpress_sid", "species": "mouse", "factors": [{"GSM359167": {"TIMEPOINT": "16h after initiation of IFNa treatment, untreated were littermate controls which received no treatment"}}, {"GSM359167": {"TIMEPOINT": "16h after initiation of IFNa treatment, untreated were littermate controls which received no treatment"}}, {"GSM359167": {"TIMEPOINT": "16h after initiation of IFNa treatment, untreated were littermate controls which received no treatment"}}, {"GSM359170": {"TIMEPOINT": "16h after initiation of IFNa treatment"}}, {"GSM359170": {"TIMEPOINT": "16h after initiation of IFNa treatment"}}, {"GSM359170": {"TIMEPOINT": "16h after initiation of IFNa treatment"}}], "id": 5595, "pop_total": 0, "platform": 6, "summary_wrapped": "Maintenance of the blood system is dependent on dormant haematopoietic stem cells (HSCs) with long-term self-renewal capacity. Upon...", "pubmed_id": 19212321, "geo_gse_id": "E-GEOD-14361", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 1, "sample_count": 6, "tags": ["cancer", "cell", "stem cell"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_id_plat": "E-GEOD-14361_A-AFFY-45", "slug": "ifna-activates-dormant-hscs-in-vivo", "geo_gds_id": "", "name": "IFNa activates dormant HSCs in vivo", "created": "Nov.10, 2014", "summary": "Maintenance of the blood system is dependent on dormant haematopoietic stem cells (HSCs) with long-term self-renewal capacity. Upon injury these cells are induced to proliferate in order to quickly re-establish homeostasis. The signalling molecules promoting the exit of HSCs out of the dormant stage remain largely unknown. Here we show that in response to treatment of mice with interferon-alpha (IFN\u03b1), HSCs efficiently exit G0 and enter an active cell cycle. HSCs respond to IFN\u03b1 treatment by increased phosphorylation of STAT1 and PKB/Akt, expression of IFN\u03b1 target genes and up-regulation of stem cell antigen-1 (Sca-1). HSCs lacking either the interferon-\u03b1/\u03b2 receptor (IFNAR), STAT1 or Sca-1 are insensitive to IFN\u03b1 stimulation, demonstrating that STAT1 and Sca-1 mediate IFN\u03b1 induced HSC proliferation. Although dormant HSCs are resistant to the anti-proliferative chemotherapeutic agent 5-FU1, HSCs pre-treated (primed) with IFN\u03b1 and thus induced to proliferate are efficiently eliminated by 5-FU exposure in vivo. Conversely, HSCs chronically activated by IFN\u03b1 are functionally compromised and are rapidly out competed by non-activatable IFNAR-/- cells in competitive repopulation assays. In summary, while chronic activation of the IFN\u03b1 pathway in HSCs impairs their function, acute IFN\u03b1 treatment promotes the proliferation of dormant HSCs in vivo. These data may help to clarify the so far unexplained clinical effects of IFN\u03b1 on leukemic cells and raise the possibility for novel applications of type I interferons to target cancer stem cells.  cDNA microarray analysis was performed on sorted Lin neg, cKit+, CD150+, CD48neg HSCs from IFN\u03b1 treated (16h after treatment) and untreated (littermate) mice. Per condition 3 independent biological replicates were analysed.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-14361", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-14361/samples/"}