Single-cell transcriptomics following ischemic injury identifies a role for B2M in cardiac repair.
Bas MolenaarLouk T TimmerMarjolein DroogIlaria PeriniDanielle VersteegLieneke KooijmanJantine Monshouwer-KlootsHesther de RuiterMonika M GladkaEva van RooijPublished in: Communications biology (2021)
The efficiency of the repair process following ischemic cardiac injury is a crucial determinant for the progression into heart failure and is controlled by both intra- and intercellular signaling within the heart. An enhanced understanding of this complex interplay will enable better exploitation of these mechanisms for therapeutic use. We used single-cell transcriptomics to collect gene expression data of all main cardiac cell types at different time-points after ischemic injury. These data unveiled cellular and transcriptional heterogeneity and changes in cellular function during cardiac remodeling. Furthermore, we established potential intercellular communication networks after ischemic injury. Follow up experiments confirmed that cardiomyocytes express and secrete elevated levels of beta-2 microglobulin in response to ischemic damage, which can activate fibroblasts in a paracrine manner. Collectively, our data indicate phase-specific changes in cellular heterogeneity during different stages of cardiac remodeling and allow for the identification of therapeutic targets relevant for cardiac repair.
Keyphrases
- single cell
- left ventricular
- rna seq
- heart failure
- gene expression
- ischemia reperfusion injury
- high throughput
- electronic health record
- cerebral ischemia
- mesenchymal stem cells
- atrial fibrillation
- big data
- risk assessment
- cell therapy
- climate change
- genome wide
- blood brain barrier
- brain injury
- endothelial cells
- machine learning
- heat shock
- bioinformatics analysis
- heat shock protein