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| Status |
Public on Nov 17, 2023 |
| Title |
Single cell transcriptomics and chromatin accessibility profiling elucidate the kidney protective mechanism of mineralocorticoid receptor antagonism [snATAC-seq] |
| Organism |
Rattus norvegicus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Mineralocorticoids play a critical role in maintaining sodium and potassium homeostasis and pathophysiological processes including hypertrophy, inflammation and fibrosis. Mineralocorticoid antagonists (MRAs) have shown to protect from kidney and heart disease, however, their molecular mechanism of action is poorly understood. Here we performed single nuclei and bulk transcriptomics and chromatin accessibility analysis to characterize the mode of kidney protection by steroidal and non-steroidal MRA treatment in a rat model of mineralocorticoid-induced cardiorenal end-organ damage. We define mineralocorticoid sensitive cell types and gene network in the kidney. We show that in diseased kidneys specific proximal tubule cells develop an injured profibrotic phenotype expressing Spp1 and Il34. Nonsteroidal finerenone protects from profibrotic differentiation of proximal tubule cells. Profibrotic gene signature can classify human kidney tissue samples and predict prognosis. Our multi-omics approach elucidates target cell types and potential mechanisms of renal protection by finerenone.
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| Overall design |
We provided three types of datasets of rat kidneys: (i) single nuclei RNA-seq as follows: 3 Control - 3 DOCA treated - 2 DOCA+Finerenone treated - 3 DOCA + Spironolactone treated, (ii) single nuclei ATAC-seq as follows: 1 Control - 1 DOCA treated - 1 DOCA+Finerenone treated - 1 DOCA + Spironolactone treated, and (iii) Bulk RNA-seq as follows: 4 Control - 4 DOCA treated - 4 DOCA+Finerenone treated - 4 DOCA + Spironolactone treated
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| Web link |
https://www.jci.org/articles/view/157165
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| Contributor(s) |
Abedini A, Wu J, Ma Z, Balzer MS, Frederick J, Cernecka H, Kolkhof P, Susztak K |
| Citation(s) |
37906287 |
| |
| Submission date |
Sep 09, 2021 |
| Last update date |
Jan 16, 2024 |
| Contact name |
Katalin Susztak |
| E-mail(s) |
ksusztak@pennmedicine.upenn.edu
|
| Organization name |
University of Pennsylvania
|
| Street address |
3400 Civic Center Blvd, SCTR
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL25947 |
Illumina NovaSeq 6000 (Rattus norvegicus) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE183842 |
Single cell transcriptomics and chromatin accessibility profiling elucidate the kidney protective mechanism of mineralocorticoid receptor antagonism |
|
| Relations |
| BioProject |
PRJNA762175 |
| SRA |
SRP338446 |
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