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| Status |
Public on Dec 06, 2011 |
| Title |
T cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
6 samples (mouse ETP thymocytes from wt, and Tcf1 inactivation) are analyzed Mouse Microarray Expression platforms, Affymetrix Mouse 430 2.0,
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| Contributor(s) |
Germar K, Dose M, Gounari F |
| Citation(s) |
22109558 |
| |
| Submission date |
Nov 07, 2011 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Jiangwen Zhang |
| E-mail(s) |
jzhang@cgr.harvard.edu
|
| Organization name |
Harvard University
|
| Department |
FAS Center for Systems Biology
|
| Street address |
7 Divinity Ave
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02138 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
|
| GSM829333 |
Tcf1-/- ETP thymocyte, biological rep1 |
| GSM829334 |
Tcf1-/- ETP thymocyte, biological rep2 |
| GSM829335 |
Tcf1-/- ETP thymocyte, biological rep3 |
| GSM829336 |
Tcf1-/+ ETP thymocyte, biological rep1 |
| GSM829337 |
Tcf1-/+ ETP thymocyte, biological rep2 |
| GSM829338 |
Tcf1-/+ ETP thymocyte, biological rep3 |
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| Relations |
| BioProject |
PRJNA148813 |
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