Normal erythropoiesis requires a critical balance between proapoptotic and antipaoptotic pathways. Bcl-xl, an antiapoptotic protein is induced at end-stages of differentiation of erythroid precursors in response to erythropoietin. The details of the proapoptotic pathway and the critical proapoptotic proteins inhibited by Bcl-xl in erythropoiesis are not well understood. We employed gene targeting to ablate Nix, a proapoptotic BH3-domain only Bcl2 family protein, which is known to be transcriptionally induced during erythropoiesis. Nix null mice exhibited reticulocytosis and thrombocytosis in the peripheral blood; and profound splenomegaly with erythroblastosis in the spleen and bone marrow despite normal erythropoietin levels and blood oxygen tension. In vivo apoptosis was diminished in erythroblast precursors from Nix null spleens. To define the molecular consequences of Nix ablation on apoptosis and erythropoiesis, we conducted a detailed comparative analysis of gene expression in spleens from 8 week old Nix null mice and wild type controls. Of 45,101 genes analyzed, 514 were significantly upregulated and 386 down-regulated in Nix-/- splenocytes. Functional cluster analysis delineated the ten most highly regulated gene sets, revealing increased levels of cell cycle and erythroid genes, with decreased levels of cell death and B-cell genes.
Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis.
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Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation.
Specimen part
View SamplesSimilar temporal expression kinetics of transcription factors in human and mouse osteoclast differentiation evaluated by microarray
Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation.
Specimen part
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Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development.
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View SamplesZebrafish embryo were analyzed at 30 and 60 % epiboly for changes in transcriptome of wild-type and MTspg mutant embryos
Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development.
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View SamplesDN3, DN4 and DP cells were sorted from 3-4 week old WT and mice and subjected to transcriptome analysis
The tumor suppressor Ikaros shapes the repertoire of notch target genes in T cells.
Specimen part
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