Single-cell transcriptomics following ischemic injury identifies a role for B2M in cardiac repair

• Published in: Communications biology Vol. 4; no. 1; p. 146
• Main Authors: Molenaar, Bas, Timmer, Louk T., Droog, Marjolein, Perini, Ilaria, Versteeg, Danielle, Kooijman, Lieneke, Monshouwer-Kloots, Jantine, de Ruiter, Hesther, Gladka, Monika M., van Rooij, Eva
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 38/91; 45/77; 631/337/2019; 631/80/86; 64/60; 96/63; 96/95; Animals; beta 2-Microglobulin - genetics; beta 2-Microglobulin - metabolism; Biology; Biomedical and Life Sciences; Cardiomyocytes; Cell Line; Cell signaling; Congestive heart failure; Disease Models, Animal; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Gene expression; Gene Expression Profiling; Induced Pluripotent Stem Cells - metabolism; Induced Pluripotent Stem Cells - pathology; Ischemia; Life Sciences; Macrophages - metabolism; Macrophages - pathology; Mice; Mice, Inbred C57BL; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Paracrine Communication; Paracrine signalling; Single-Cell Analysis; Therapeutic applications; Time Factors; Transcription; Transcriptome; Ventricular Remodeling; Wound Healing
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-01636-3

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. Molenaar et al. use scRNA-seq to profile cardiac cell gene expression changes at three time points following ischemic injury. They observe that B2M is secreted by cardiomyocytes following injury, promoting scar formation. This data may be useful in finding therapeutic targets for cardiac repair