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| Status |
Public on Dec 01, 2023 |
| Title |
Glomerular podocyte RNA-seq data of the podocyte-specific Profilin1 deficient mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The progression of proteinuric kidney disease is associated with podocyte loss but the mechanisms remain unclear. Podocytes reenter the cell cycle to repair damaged ds DNA breaks. However, unsuccessful repair results in podocytes crossing the G1/S checkpoint and undergoes abortive cytokinesis. In this study, we identified Pfn1 as a major contributor in maintaining glomerular integrity and its loss in mice results in severe proteinuria, and kidney failure due to podocyte mitotic catastrophe, characterized by abundant multinucleated cells. Reentry of podocytes were identified by using FUCCI-2aR mice, accompanying the alteration of cell-cycle associated proteins, such as P21, P53, Cyclin B, and Cyclin D. Podocyte-specific translating ribosome affinity purification (TRAP) and RNAseq revealed a reduction of Ribosomal RNA-processing protein 8 (Rrp8) and re-expression of Rrp8 partially rescued the in-vitro phenotype. Clinical analysis of patients with proteinuric kidney disease demonstrated multinucleated podocytes and reduced podocyte profilin1 in kidney tissue. These results suggest that profilin is indispensible in regulating podocyte cell cycle and its disruption contributes to podocyte loss through mitotic catastrophe.
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| Overall design |
The freshly podocytes samples were isolated from the Control mice and Pfn1 C KO mice at 3 weeks of age for the RNAseq analysis. Each sample contained 3 mice in order to get the sufficient podocytes samples, and 2 control samples and 3 Pfn1 KO samples were analyzed and summarized.
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| Contributor(s) |
Ishibe S, Tian X, Gu J, Zhang Y |
| Citation(s) |
37847555 |
| |
| Submission date |
Mar 15, 2023 |
| Last update date |
Jan 02, 2024 |
| Contact name |
Xuefei Tian |
| E-mail(s) |
xuefei.tian@yale.edu
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| Phone |
203-737-5648
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| Organization name |
Yale University School of Medicine
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| Department |
Nephrology/Internal Medicine
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| Lab |
Shuta Ishibe
|
| Street address |
300 Cedar Street
|
| City |
New Haven |
| State/province |
CT |
| ZIP/Postal code |
06510 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA945004 |
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