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| Status |
Public on Aug 09, 2023 |
| Title |
Prmt5 deficiency inhibits CD4+T cells migration through Klf2-S1pr1 and ameliorates EAE disease (scRNA-seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Protein arginine methyltransferase 5 (Prmt5) is the major type II methyltransferase catalyzing symmetric dimethylation, regulates cell development, homeostatic and disease processes. Prmt5 inhibition or deletion in CD4+T cells has been reported to protection against experimental autoimmune encephalomyelitis (EAE), the perfect mouse model for multiple sclerosis (MS); however, the detail mechanisms have not yet been elucidated. Here, using the mRNA sequencing, single cell RNA sequencing and ATAC sequencing, we uncovered the unreported role of Prmt5 on T cells migration ability under the EAE condition. We found that mice condition knockout of Prmt5 in T cells were resistance with EAE, infiltrating inflammatory CD4+ T cells in center nervous system (CNS) were greatly reduced. However, T cells in spleen showed much more proliferation and activation properties in Prmt5cko mice, the number of pathogenic CD4+T cells in spleen were not reduced. We further revealed that Rora+CD4+T cells were elevated in Prmt5cko mice, but expressed lower level of S1pr1, resulting in a lack of CD4+ T cells egress from spleen and migrate to CNS, leading to pathogenic CD4+T cells were blocked in spleen. Moreover, single cell ATAC sequencing revealed that Klf2 were enriched in S1pr1 promoter and reduced in Prmt5cko mice. Correctively, our study delineated the undiscovered role of Prmt5 on T cell biology, Prmt5 may through Klf2-S1pr1 pathway and regulate T cells migration; modulating Prmt5 levels may be useful for controlling CD4+T cell migration in CD4+T cell mediated diseases including MS.
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| Overall design |
Prmt5 CKO and control mice (3 mice per group) were induced EAE by MOG35–55/CFA immunization, on the day the score peaked, purified CD8+ and CD4+ T cells isolated from spleen were performed bulk RNA sequencing and all cells isolated from spleen were performed single cell RNA sequencing and single cell ATAC sequcing.
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| Contributor(s) |
Zheng Y, Chen Z |
| Citation(s) |
37533053 |
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| Submission date |
Feb 01, 2022 |
| Last update date |
Aug 09, 2023 |
| Contact name |
zheyi chen |
| E-mail(s) |
zheyi_chen0601@163.com, chenzheyi@sjtu.edu.cn
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| Organization name |
Shanghai Jiao Tong University School of Medicine
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| Street address |
1665 Kong Jiang Road
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| City |
Shanghai |
| ZIP/Postal code |
200092 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE195888 |
Prmt5 deficiency inhibits CD4+T cells migration through Klf2-S1pr1 and ameliorates EAE disease |
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| Relations |
| BioProject |
PRJNA802549 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE195887_barcodes.tsv.gz |
194.8 Kb |
(ftp)(http) |
TSV |
| GSE195887_genes.tsv.gz |
115.7 Kb |
(ftp)(http) |
TSV |
| GSE195887_matedata.csv.gz |
204.9 Kb |
(ftp)(http) |
CSV |
| GSE195887_matrix.mtx.gz |
138.4 Mb |
(ftp)(http) |
MTX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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