Human Gene Set: GSE33513_TCF7_KO_VS_HET_EARLY_THYMIC_PROGENITOR_DN


Standard name GSE33513_TCF7_KO_VS_HET_EARLY_THYMIC_PROGENITOR_DN
Systematic name M5107
Brief description Genes down-regulated in comparison of TCF7 [GeneID=6932] deficient early thymic progenitors versus the TCF7 [GeneID=6932] sufficient ones.
Full description or abstract Although transcriptional programs associated with T-cell specification and commitment have been described, the functional hierarchy and the roles of key regulators in structuring/ orchestrating these programs remain unclear. Activation of Notch signaling in uncommitted precursors by the thymic stroma initiates the T-cell differentiation program. One regulator first induced in these precursors is the DNA binding protein Tcf-1, a T-cell specific mediator of Wnt signaling. Yet the specific contribution of Tcf-1 to early T-cell development and the signals inducing it in these cells remain unclear. Here we assign functional significance to Tcf-1 as a gatekeeper of T-cell fate. We show that Tcf-1 is directly activated by Notch signals. Tcf-1 is required at the earliest phase of Tcell determination for progression beyond the early thymic progenitor (ETP) stage. The global expression profile of Tcf-1 deficient progenitors indicates that basic processes of DNA metabolism are downregulated in its absence and the blocked T-cell progenitors become abortive and die by apoptosis. Our data thus add an important functional relationship to the roadmap of T-cell development. We used microarrays to detail the global programme of gene expression of mouse ETP thymocyte after Ikaros inactivation with dominant negative of Ik at different stage.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 22109558   Authors: Germar K,Dose M,Konstantinou T,Zhang J,Wang H,Lobry C,Arnett KL,Blacklow SC,Aifantis I,Aster JC,Gounari F
Exact source GSE33513_2166_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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