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Spatiotemporal transcriptome analysis reveals critical roles for mechano-sensing genes at the border zone in remodeling after myocardial infarction

ABSTRACT: The underlying mechanisms of ventricular remodeling after myocardial infarction (MI) remain largely unknown. Here, we performed an integrative analysis of spatial transcriptomics and single-nucleus RNA-seq in a murine MI model and found that mechanical stress-response genes are expressed at the border zone and play a critical role in left ventricular remodeling following MI. An integrative analysis of single-nucleus RNA-seq and spatial transcriptome of the heart tissue after MI identified the unique cluster that appeared at the border zone in an early stage, highly expressing mechano-sensing genes such as Csrp3. AAV9-mediated gene silencing and overexpression of Csrp3 demonstrated that upregulation of Csrp3 plays critical roles in preventing cardiac remodeling after MI via regulation of genes associated with mechano-sensing. Overall, our study not only provides an insight into spatiotemporal molecular changes following MI but also highlights that the mechano-sensing genes at the border zone act as adaptive regulators of left ventricular remodeling.

ORGANISM(S): Mus musculus

PROVIDER: GSE176092 | GEO | 2022/07/25

REPOSITORIES: GEO

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