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Single-cell and spatial transcriptomic profiling of cardiac fibroblasts following myocardial infarction
We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.
Executive Impact at a Glance
Leverage the power of cutting-edge multi-omics research to drive innovation in cardiovascular health and regenerative medicine.
27995
Cardiac Fibroblasts Profiled
3
Datasets Integrated
5
Days Post-Infarction Studied
17
Cell Clusters Identified
Deep Analysis & Enterprise Applications
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Peak Activation Period for RCF Marker Genes
3-5 dpiBulk RNA-seq analysis revealed that highly relevant Reparative Cardiac Fibroblast (RCF) marker genes, including Cthrc1, Ddah1, Postn, Fn1, Lox, and Ptn, exhibited peak expression between 3 and 5 days post-infarction (dpi). This defines a critical window for RCF activation.
RCF Activation & Differentiation Pathway
Myocardial Infarction (MI)
→
Activation of Periostin (Postn)+ CFs
→
Transition to Cthrc1+ Reparative CFs (RCFs)
→
Scar Formation & Ventricular Repair
| Methodology | Contribution to Understanding CFs |
|---|---|
| Bulk RNA Sequencing |
|
| Single-cell RNA Sequencing |
|
| Spatial Transcriptomics |
|
Asporin (Aspn) as a Key Regulator
D2 DynamicsAsporin (Aspn) was identified as a critical gene within the D2 transcriptional dynamics, associated with TGF-β signaling and ECM molecules. Aspn loss-of-function leads to a Cthrc1-KO-like phenotype of ventricular rupture, highlighting its importance in cardiac remodeling.
Translational Validation Across Species
The identified D2-associated gene expression patterns, including Asporin up-regulation, were consistently detected across mouse, pig, and human cardiac datasets. This cross-species and multi-platform validation underscores the translational relevance of the findings for cardiac research.
Impact: This robust validation across different animal models and human samples significantly enhances the applicability of the dataset for developing novel therapeutic strategies targeting cardiac fibrosis in humans, accelerating the transition from bench to bedside.
Dataset Availability
Publicly AvailableAll data, including single-cell RNA-seq (GSE261428), bulk RNA-seq (GSE267256), and spatial transcriptomics (GSE265828), are publicly available on NCBI's Gene Expression Omnibus, along with code on GitHub, ensuring broad reusability for the scientific community.
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