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| Status |
Public on May 21, 2021 |
| Title |
Chromatin assembly factor 1B critically controls early development but not functional acquisition of iNKT cells [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
T cell development is a complicatedly hierarchical process which is closely related with the chromatin activation and gene transcription. CD4+CD8+ double-positive (DP) thymocytes give rise to both conventional TCRαβ+ T cells and natural killer T cells, but they display different characteristics. Compared with conventional TCRαβ+ T cells, invariant natural killer T cells (iNKT cells) as the major population of NKT cells, are CD1d-restricted, recognize glycolipid antigens and rapidly exert effector functions after stimulation. However, the specific molecular mechanism of early iNKT cell development remain incompletely understood. Here the authors show that deletion of Chromatin assembly factor 1B (CHAF1b) remains the normal development of conventional TCRαβ+ T cell, but specifically impacts iNKT cell generation and completely impairs iNKT cell development from stage 0 with a PLZF independent way. This dysregulation is accompanied by a specific decrease in gene transcription of Vα14-Jα18, an impairment in TCR signaling and PLZF expression. Notably, ectopic expression of a transgenic Vα14-Jα18 TCR completely rescues these defects in Chaf1b-deficient iNKT cells. Moreover, cytokine secretion and anti-tumor activity are substantially maintained in Chaf1b-deficient iNKT cells with transgenic Vα14-Jα18 TCR. Our study identifies CHAF1b as a distinct regulator controls early development of iNKT cells via transcriptional regulation of Vα14-Jα18.
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| Overall design |
DP thymocytes of wild type (WT) and Chaf1b-deficient (KO) mice were analyzed chromatin accessibility by ATAC-seq with two replications.
Please note that each processed data file was generated from both replicates and is linked to the corresponding first replicate (*repeat1) sample records.
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| Contributor(s) |
Xu Y, Ma J, Luo H, Shi Y, Liu H, Sun A, Liu X |
| Citation(s) |
33949677 |
| |
| Submission date |
Apr 23, 2020 |
| Last update date |
Aug 22, 2021 |
| Contact name |
Yu Xu |
| E-mail(s) |
xuyu2013@sibcb.ac.cn
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| Phone |
14782794066
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| Organization name |
Shanghai Institue of Biochemistry and Cell Biology
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| Street address |
320 Yueyang Road
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| City |
Shanghai |
| ZIP/Postal code |
200031 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE149177 |
Chromatin assembly factor 1B critically controls early development but not functional acquisition of iNKT cells |
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| Relations |
| BioProject |
PRJNA627601 |
| SRA |
SRP258034 |
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