This SuperSeries is composed of the SubSeries listed below.
Combined targeting of JAK2 and Bcl-2/Bcl-xL to cure mutant JAK2-driven malignancies and overcome acquired resistance to JAK2 inhibitors.
Specimen part, Disease, Disease stage
View SamplesMaintenance 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), HSCs efficiently exit G0 and enter an active cell cycle. HSCs respond to IFN treatment by increased phosphorylation of STAT1 and PKB/Akt, expression of IFN target genes and up-regulation of stem cell antigen-1 (Sca-1). HSCs lacking either the interferon-/ receptor (IFNAR), STAT1 or Sca-1 are insensitive to IFN stimulation, demonstrating that STAT1 and Sca-1 mediate IFN induced HSC proliferation. Although dormant HSCs are resistant to the anti-proliferative chemotherapeutic agent 5-FU1, HSCs pre-treated (primed) with IFN and thus induced to proliferate are efficiently eliminated by 5-FU exposure in vivo. Conversely, HSCs chronically activated by IFN 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 pathway in HSCs impairs their function, acute IFN treatment promotes the proliferation of dormant HSCs in vivo. These data may help to clarify the so far unexplained clinical effects of IFN on leukemic cells and raise the possibility for novel applications of type I interferons to target cancer stem cells.
IFNalpha activates dormant haematopoietic stem cells in vivo.
Specimen part, Time
View SamplesWe sequenced liver mRNA isolated from biliatresone-treated zebrafish larvae and DMSO-treated controls in order to elucidate the molecular pathways induced by biliatresone, a biliary toxin that is responsible for outbreaks of biliary atresia in Australian liverstock. Overall design: Liver mRNA profiles of biliatresone-treated zebrafish larvae and DMSO-treated controls were generated by deep sequencing, in duplicates.
Glutathione antioxidant pathway activity and reserve determine toxicity and specificity of the biliary toxin biliatresone in zebrafish.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sirt1 Regulates DNA Methylation and Differentiation Potential of Embryonic Stem Cells by Antagonizing Dnmt3l.
No sample metadata fields
View SamplesStem-cells and transformed cancer cells specifically express a polycomb repressive complex subtype, PRC4 which characteristically contains Sirt1 (Sirtuin-1), a NAD+ dependent class III histone deacetylase (HDAC) and Eed2 isoform as specific members. Analyzing the transcriptiome and methylome analysis of Sirt1 deficient murine ESCs (Sirt1-/- ESC), we demonstrate that these cells repressed specifically on some genomic imprinted and germ-line related genes.
Sirt1 Regulates DNA Methylation and Differentiation Potential of Embryonic Stem Cells by Antagonizing Dnmt3l.
No sample metadata fields
View Samples