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| Status |
Public on Sep 17, 2018 |
| Title |
Transient expression of T-bet epigenetically imprints the Ifng locus for its expression in a distinct Tfh cell subset |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
T follicular helper (Tfh) cells, which reside in the B cell follicles and help Ig class switching, express the master transcription factor BCL-6 and signature cytokine IL-21. Tfh cells are also capable of expressing IFN-g, however, whether IFN-g-producing Tfh population represents a unique Tfh subset and how they develop are unknown. While T-bet is the master regulator for IFN-g production in Th1 cells, Tfh cells express no or very low levels of T-bet. Here, by using a T-bet-fate-mapping mouse strain, we report that all the IFN-g-producing Tfh cells identified after immunization have previously expressed T-bet. DNase I hypersensitivity analysis indicates that the Ifng gene locus is partially accessible in this ‘ex-T-bet’ population but inaccessible in Tfh cells without a history of T-bet expression. Furthermore, multi-color tissue imaging shows that some “ex-T-bet” Tfh cells reside in germinal centers and express IFN-gin situ. Finally, IFN-g-expressing Tfh cells are absent in T-bet-deficient mice and the Ifng gene is inaccessible in T-bet-deficient Tfh cells. Thus, transient expression of T-bet epigenetically imprints the Ifng locus for cytokine production in Tfh cells. Our results also indicate that Tfh cells are composed of different subsets and they may use genetic programs similar to those of classical non-Tfh T helper cells in order to acquire unique cytokine producing capacity.RNA-Seq analysis of gene expression in splenic CD4+CD44highCD25- T cell subsets. RNA-Seq analysis of gene expression in antigen-specific Tfh cells and non-Tfh cells that have a history of T-bet expression. DNase 1-Seq of T-bet expressed and un-expressed Tfh cells and non-Tfh cells.
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| Overall design |
RNA-Seq analysis of gene expression in splenic CD4+CD44highCD25- T cells from naive mice that are either expressing T-bet or have a history of T-bet expression. RNA-Seq analysis of gene expression in antigen (AS15)-specific Tfh and non-Tfh cell subsets that were separated based on their history of T-bet expression. scDNase-seq analysis of antigen (AS15)-specific Tfh and non-Tfh cell subsets that were separated based on their history of T-bet expression. AS15-specific cells from draining lymph nodes of AS-15/CFA-immunized mice on day 16 were identified by tetramer staining. All the cell subsets were harvested by cell sorting after staining.
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| Contributor(s) |
Fang D, Cui K, Mao K, Hu G, Li R, Zheng M, Riteau N, Reiner SL, Sher A, Zhao K, Zhu J |
| Citation(s) |
30232200 |
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| Submission date |
Aug 22, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Gangqing Hu |
| E-mail(s) |
michael.hu@hsc.wvu.edu
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| Organization name |
West Virginia University
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| Department |
MicroBiology, Immunology, and Cell Biology
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| Lab |
2072A, HSC North, Floor 2
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| Street address |
64 Medical Center Drive
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| City |
Morgantown |
| State/province |
West Virginia |
| ZIP/Postal code |
26506-9177 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA399539 |
| SRA |
SRP115960 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE102959_RAW.tar |
7.6 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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