BACKGROUND: Hox genes are implicated in hematopoietic stem cell (HSC) regulation as well as in leukemia development through translocation with the nucleoporin gene NUP98. Interestingly, an engineered NUP98-HOXA10 (NA10) fusion can induce a several hundred-fold expansion of HSCs in vitro and NA10 and the AML-associated fusion gene NUP98-HOXD13 (ND13) have a virtually indistinguishable ability to transform myeloid progenitor cells in vitro and to induce leukemia in collaboration with MEIS1 in vivo. METHODOLOGY/PRINCIPAL FINDINGS: These findings provided a potentially powerful approach to identify key pathways mediating Hox-induced expansion and transformation of HSCs by identifying gene expression changes commonly induced by ND13 and NA10 but not by a NUP98-Hox fusion with a non-DNA binding homedomain mutation (N51S). The gene expression repertoire of purified murine bone marrow Sca-1+Lin- cells transduced with retroviral vectors encoding for these genes was established using the Affymetrix GeneChip MOE430A. Approximately seventy genes were differentially expressed in ND13 and NA10 cells that were significantly changed by both compared to the ND13(N51S) mutant. Intriguingly, several of these potential Hox target genes have been implicated in HSC expansion and self-renewal, including the tyrosine kinase receptor Flt3, the prion protein, Prnp, hepatic leukemia factor, Hlf and Jagged-2, Jag2. CONCLUSIONS: In conclusion this study has identified several novel Hox downstream target genes and provides important new leads to key regulators of the expansion and transformation of hematopoietic stem cells by Hox.
Candidate genes for expansion and transformation of hematopoietic stem cells by NUP98-HOX fusion genes.
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View SamplesPolycomb-mediated repression of Dkk-1 activates Wnt signaling and enhances tumorigenic potential of lung cancer cells following tobacco smoke exposure
Tobacco smoke induces polycomb-mediated repression of Dickkopf-1 in lung cancer cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma.
Sex
View SamplesCompariosn of mRNA and miRNA profile in colon cancer
Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels.
Specimen part, Cell line
View SamplesMicroarray studies was performed to analyze gene expression changes in NCI-H2347 cells after treatment with 50 M pioglitazone for 12hr, 24hr and 48hrs.
Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels.
Specimen part, Cell line
View SamplesMouse haematopoietic stem cells (HSCs) undergo a post-natal transition in several properties, including a marked reduction in their self-renewal activity. We now show that the developmentally timed change in this key function of HSCs is associated with their decreased expression of Lin28b and an accompanying increase in their let-7 microRNA levels. Lentivirus(LV)-mediated overexpression of Lin28 in adult HSCs elevates their self-renewal activity in transplanted irradiated hosts, as does overexpression of Hmga2, a well-established let-7 target that is upregulated in fetal HSCs. Conversely, HSCs from fetal Hmga2-/- mice do not display the heightened self-renewal activity that is characteristic of wild-type fetal HSCs. Interestingly, overexpression of Hmga2 in adult HSCs does not mimic the ability of elevated Lin28 to activate a fetal lymphoid differentiation program. Thus Lin28b may act as a master regulator of developmentally timed changes in HSC programs with Hmga2 serving as its specific downstream modulator of HSC self-renewal potential.
The Lin28b-let-7-Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells.
Specimen part
View SamplesThe methyltransferase G9a was found to play a role in the disease progression of a murine model of AML.
The methyltransferase G9a regulates HoxA9-dependent transcription in AML.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling.
Specimen part, Time
View SamplesBiological processes are optimized by circadian and circannual biological timing systems. In vertebrates, the pineal gland plays an essential role in these systems by converting time into a hormonal signal, melatonin; in all vertebrates, circulating melatonin is elevated at night, independent of lifestyle. At night, sympathetic input to the pineal gland, originating from the circadian clock in the suprachiasmatic nucleus, releases norepinephrine. This adrenergic stimulation causes an elevation of cAMP, which is thought to regulate many of the dramatic changes in genes expression known to occur at night. In many aspects, the adrenergic/cAMP effects on gene expression can be recapitulated in primary organ culture.
Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling.
Specimen part, Time
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