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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 27, 2021 |
| Title |
ADAR1 RNA editing quenches innate immune activation in endothelial cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
RNA editing has been shown to implicate in cardiovascular diseases, including dysregulated RNA editing in endothelial cell (EC) that involves Adenosine Deaminase Acting on RNA1 (ADAR1). However, the specific function of ADAR1 in EC at physiologic condition has not been established and the mechanism remains to be defined. This study is to determine the specific physiologic role of ADAR1 in EC and reveal its molecular and cellular mechanisms.
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| Overall design |
A mouse model carrying an EC-specific deletion of ADAR1 gene was established through breeding Cdh-5 Cre transgenic and floxed ADAR1 mice. Deletion of ADAR1 in ECs resulted in newborn death with multiple organ injuries. Genome-wide gene expression analysis revealed an obvious innate immune activation with dramatic elevation of Interferon Stimulated Genes (ISGs) expression. ADAR1 deficiency impacted the proliferation, migration and tube-formation capacities of EC. Genome-wide analysis of EC RNA transcript found extensive RNA editing in EC and ADAR1 deficiency dramatically reduced RNA editing on SINE transcripts that modifies the corresponding dsRNA structures. Notably, we demonstrated that the altered cellular RNA activates the RNA sensing signaling pathway and deletion of the cellular RNA receptor Melanoma Differentiation-Associated protein 5 (MDA-5) prevented the immune activation in EC, and completely rescued the EC ADAR1 deficient mice from death. Gene expression analysis confirmed that the rescue was associated with the blockage of RNA sensing pathway as shown by the restored ISG expression levels in EC.
Two inducible ADAR1 knockout mice from two independent litters were used for EC isolation (annotated as EC1 and EC2). RNA samples were isolated from 4-OH-Tamoxifen treated (TM) and nontreated control (CON) cells for sequencing.
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| Contributor(s) |
Guo X, Liu S, Yan R, Nguyen V, Zhang L, Wang T, Zenatai M, Billiar TR, Wang Q |
| Citation(s) |
34969816 |
| Submission date |
May 10, 2021 |
| Last update date |
Feb 02, 2022 |
| Contact name |
Shuchang Liu |
| E-mail(s) |
shl96@pitt.edu
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| Organization name |
University of Pittsburgh
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| Department |
Pathology
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| Street address |
203 Lothrop Street
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| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15261 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA728800 |
| SRA |
SRP319310 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE174216_RAW.tar |
360.0 Kb |
(http)(custom) |
TAR (of TXT) |
| GSE174216_Site_Pool.csv.gz |
20.2 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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