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| Status |
Public on Dec 19, 2016 |
| Title |
The Gfi1-Foxo1 axis controls the fidelity of effector gene expression and developmental maturation of thymocytes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Double-positive (DP) thymocytes respond to intrathymic TCR signals by undergoing positive selection and lineage differentiation into single-positive (SP) mature cells. Concomitant with these wellcharacterized events is the acquisition of a mature T cell gene expression program characterized by the induction of effector molecules IL-7Ra, S1P1 and CCR7, but the underlying mechanism remains elusive. We report here that transcription repressor Gfi1 orchestrates the fidelity of DP gene expression program and developmental maturation into SP cells. Loss of Gfi1 resulted in premature induction of effector genes and transcription factors Foxo1 and Klf2 in DP thymocytes, and accumulation of post-selection intermediate populations and accelerated transition into SP cells. Strikingly, partial loss of Foxo1 function, but not restored survival fitness, rectified the dysregulated gene expression and thymocyte maturation in Gfi1-deficient mice. Our results establish Gfi1-Foxo1 axis and the transcriptional circuitry that actively maintain DP identity and shape the proper generation of mature T cells
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| Overall design |
We used microarrays to compare the global transcription profiles of CD4+CD8+ double-positive (DP) thymocytes isolated from wild-type mice, and thymocytes from hCD2-iCre x Gfi1fl/fl mice
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| Contributor(s) |
Shi L, Saravia J, Guy CS, Neale G, Chi H |
| Citation(s) |
27994150 |
| Submission date |
Nov 16, 2016 |
| Last update date |
Aug 06, 2018 |
| Contact name |
Geoffrey Neale |
| E-mail(s) |
geoffrey.neale@stjude.org
|
| Organization name |
St Jude Childrens Research Hospital
|
| Department |
Hartwell Center
|
| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11180 |
[HT_MG-430_PM] Affymetrix HT MG-430 PM Array Plate |
|
| Samples (4)
|
| GSM2392781 |
Thymocytes from WT mouse, replicate 1 |
| GSM2392782 |
Thymocytes from hCD2-iCre x Gfi1fl/fl mouse, replicate 1 |
| GSM2392783 |
Thymocytes from WT mouse, replicate 2 |
| GSM2392784 |
Thymocytes from hCD2-iCre x Gfi1fl/fl mouse, replicate 2 |
|
| Relations |
| BioProject |
PRJNA354279 |
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