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| Status |
Public on Oct 01, 2020 |
| Title |
Transient ACE Inhibition Suppresses Future Fibrogenic Capacity and Heterogeneity of Cardiac Fibroblast Subpopulations |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Transient angiotensin converting enzyme (ACE) inhibition in spontaneously hypertensive rats (SHR) protects against future injury-induced cardiac inflammation, fibrosis, and dysfunction. Here, we used single cell RNA sequencing (scRNA-Seq) to test the hypothesis that transient ACE inhibitor treatment would induce a persistent shift in hypertensive cardiac fibroblast subpopulations. Adult male SHRs (11 weeks old) were treated for 2 weeks with an ACE inhibitor, enalapril (30mg/kg/day, p.o.), or water (control) followed by a 2-week washout period (n=7/group). Cardiac fibroblasts were isolated from the left ventricle and subjected to scRNA-Seq. Nine clusters of fibroblasts (numbered 0-8) were identified with 98% of cells clustering into subsets 0-6. Transient treatment produced significant changes within and across clusters. Cluster 1 depicted the highly fibrogenic gene profile, with cluster 6 serving as a gateway to cluster 1. Transient ACE inhibition depleted the gateway and expanded cluster 0, which was the least fibrogenic profile. Moreover, within cluster 1 fibroblasts, ACE inhibition reduced expression of individual fibrosis genes (e.g. COL1A1, COL3A1, and FN1; all p<0.05). Clusters 2-5 reflected proliferative, moderately fibrogenic, translationally active, and lowly inflammatory subsets of fibroblasts, all of which exhibit attenuated fibrogenic gene expression after transient ACE inhibition. In conclusion, transient ACE inhibition shifts cardiac fibroblast subpopulations and degree of activation resulting in an overall reduced fibrogenic phenotype.
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| Overall design |
Single cell RNA-sequencing of cardiac fibroblasts from SHR with and without prior transient ACE inhibitor treatment.
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| Contributor(s) |
Garvin AM, De Both MD, Talboom JS, Lindsey ML, Huentelman MJ, Hale TM |
| Citation(s) |
33486989 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R56 HL141165 |
Identifying a Pathogenic Fibroblast Subpopulation to Target for Protection Against Cardiac Fibrosis |
ABOR, UNIVERSITY OF ARIZONA |
Taben M. Hale |
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| Submission date |
Aug 04, 2020 |
| Last update date |
Feb 21, 2021 |
| Contact name |
Taben Mary Hale |
| E-mail(s) |
taben.hale@arizona.edu
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| Organization name |
University of Arizona
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| Department |
Basic Medical Sciences
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| Street address |
425 N 5th St
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| City |
Phoenix |
| State/province |
AZ |
| ZIP/Postal code |
85004 |
| Country |
USA |
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| Platforms (1) |
| GPL22396 |
Illumina HiSeq 4000 (Rattus norvegicus) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA655239 |
| SRA |
SRP275843 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE155699_RAW.tar |
191.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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