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| Status |
Public on Jun 08, 2024 |
| Title |
Effect of GRP75 deficiency on gene expression in DN3 thymocytes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Mitochondria and endoplasmic reticulum contacts (MERCs) regulate multiple cellular processes including cell survival and differentiation. Based on the observations that MERCs were specifically enriched in the CD4-CD8- double negative (DN) stage, we studied their role in early thymocyte development. We found that T-cell-specific knockout of Hspa9, which encodes GRP75, a chaperone mediates MERC formation by assembling the IP3R-GRP75-VDAC complex, impaired DN3 thymocyte viability and resulted in thymocyte developmental arrest at the DN3-DN4 transition. Mechanistically, GRP75 deficiency induced mitochondrial stress, releasing mitochondrial DNA (mtDNA) into the cytosol and triggering the type I interferon (IFN-I) response. IFN-I pathway contributed to both the impairment of cell survival and DN3-DN4 transition blockage, while increased lipid peroxidation (LPO) played a major role downstream of IFN-I. Thus, our study reveals the essential role of GRP75-dependent MERCs in early thymocyte development and uncovers the governing facts of cellular survival and differentiation in the DN stage.
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| Overall design |
To inveatigate the role of GRP75 in early thymocyte development, we isolated DN3 (Lin-, CD4-, CD8-, CD44-, CD25+) thymocytes from 5-week-old WT and Hspa9 cKO mice. Then we performed gene expression profiling analysis using data obtained from RNA-seq of WT and Hspa9 cKO DN3 thymocytes.
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| Contributor(s) |
Zhao F, Cui Z, Wang P, Lu L |
| Citation(s) |
38981469 |
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| Submission date |
May 23, 2024 |
| Last update date |
Sep 10, 2024 |
| Contact name |
wang pengfei |
| E-mail(s) |
zjuwpf@outlook.com
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| Organization name |
zhejiang university
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| Street address |
yuhangtang road 866
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| City |
hangzhou |
| ZIP/Postal code |
310058 |
| Country |
China |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1115108 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE268197_RAW.tar |
10.4 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
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