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Series GSE33802 Query DataSets for GSE33802
Status Public on Dec 27, 2011
Title Early T-helper 1 Differentiation Is Marked by A Follicular Helper-like Transition: Differential Roles of STAT4 and T-bet
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Follicular helper T (Tfh) cells comprise an important subset of helper T cells; however, their relationship with other helper lineages is incompletely understood. Herein, we show IL-12 acting via signal transducer and activator of transcription 4 (STAT4) induced both Il21 and Bcl6 genes, generating cells with features of both Tfh and Th1 cells. However, STAT4 also induced T-bet. Using ChIP-seq, we defined the genome-wide targets of T-bet and found that it repressed Bcl6 and other markers of Tfh cells, thereby attenuating the nascent Tfh-like phenotype in the late phase of Th1 specification. Finally, Tfh-like T cells were rapidly generated following Toxoplasma gondii infection in mice, but T-bet constrained Tfh cells expansion and consequent germinal center formation and antibody production. Our data argue that Tfh and Th1 share a transitional stage through the signal mediated by STAT4, which promotes both phenotypes. However, T-bet represses Tfh functionalities, promoting full Th1 differentiation.
Overall design The roles of STAT4 and T-bet to determine T helper cell fate were investigated by comparing DNA binding profiles of STAT4 and T-bet in Th1 conditions. The functional outcome was further evaluated by profiling DNase hypersensitivity sites and histone epigenetic marks between WT and STAT4-deficient or T-bet-deficient T cells in Th1 conditions.
Contributor(s) Nakayamada S, Kanno Y, Sun H, Vahedi G, O’Shea JJ
Citation(s) 22195747
Submission date Nov 18, 2011
Last update date May 15, 2019
Contact name Yuka Kanno
Phone 301-402-3008
Organization name NIH
Department NIAMS
Street address 10 Center Drive, Rm13C120
City Bethesda
State/province MD
ZIP/Postal code 20892-1930
Country USA
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (9)
GSM836116 DHS WT naive
GSM836117 DHS WT Th1
GSM836118 H3K4me3 WT Th1
SRA SRP009417
BioProject PRJNA148117

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Supplementary file Size Download File type/resource
GSE33802_RAW.tar 19.8 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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