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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 01, 2015 |
| Title |
ICOS coreceptor signaling inactivates the transcription factor FOXO1 to promote Tfh cell differentiation |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
T follicular helper (Tfh) cells are essential in the induction of high-affinity, class-switched antibodies. The differentiation of Tfh cells is a multi-step process that depends upon the co-receptor ICOS and the activation of phosphoinositide-3 kinase leading to the expression of key Tfh cell genes. We report that ICOS signaling inactivates the transcription factor FOXO1, and a Foxo1 genetic deletion allowed for generation of Tfh cells with reduced dependence on ICOS ligand. Conversely, enforced nuclear localization of FOXO1 inhibited Tfh cell development even though ICOS was overexpressed. FOXO1 regulated Tfh cell differentiation through a broad program of gene expression exemplified by its negative regulation of Bcl6. Final differentiation to germinal center Tfh cells (GC-Tfh) was instead FOXO1 dependent as the Foxo1(-/-) GC-Tfh cell population was substantially reduced. We propose that ICOS signaling transiently inactivates FOXO1 to initiate a Tfh cell contingency that is completed in a FOXO1-dependent manner.
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| Overall design |
Performed ChIP-seq analysis to examine the role of foxo1 in the development of Tfh cells
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| Contributor(s) |
Stone EL, Pepper M, Katayama CD, Kerdiles YM, Lai C, Emslie E, Lin YC, Yang E, Goldrath AW, Li MO, Cantrell DA, Hedrick SM |
| Citation(s) |
25692700, 28973925 |
| Submission date |
Apr 30, 2013 |
| Last update date |
May 24, 2019 |
| Contact name |
Carol Katayama |
| E-mail(s) |
ckatayama@ucsd.edu
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| Phone |
858-534-5961
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| Fax |
858-534-0980
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| Organization name |
UC San Diego
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| Department |
BIO/CMM
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| Lab |
Hedrick
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| Street address |
9500 Gilman Dr.
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92024 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA200730 |
| SRA |
SRP021925 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46525_RAW.tar |
287.9 Mb |
(http)(custom) |
TAR (of BED, BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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