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

Bas Molenaar, Louk T Timmer, Marjolein Droog, Ilaria Perini, Danielle Versteeg, Lieneke Kooijman, Jantine Monshouwer-Kloots, Hesther de Ruiter, Monika M Gladka, Eva van Rooij

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)146
JournalCommunications Biology
Volume4
Issue number1
DOIs
Publication statusPublished - 29 Jan 2021

Keywords

  • Animals
  • Cell Line
  • Disease Models, Animal
  • Fibroblasts/metabolism
  • Gene Expression Profiling
  • Induced Pluripotent Stem Cells/metabolism
  • Macrophages/metabolism
  • Mice, Inbred C57BL
  • Myocardial Reperfusion Injury/genetics
  • Myocytes, Cardiac/metabolism
  • Paracrine Communication
  • Single-Cell Analysis
  • Time Factors
  • Transcriptome
  • Ventricular Remodeling
  • Wound Healing
  • beta 2-Microglobulin/genetics

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