Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury

Elife. 2019 Mar 26:8:e43882. doi: 10.7554/eLife.43882.

Abstract

Besides cardiomyocytes (CM), the heart contains numerous interstitial cell types which play key roles in heart repair, regeneration and disease, including fibroblast, vascular and immune cells. However, a comprehensive understanding of this interactive cell community is lacking. We performed single-cell RNA-sequencing of the total non-CM fraction and enriched (Pdgfra-GFP+) fibroblast lineage cells from murine hearts at days 3 and 7 post-sham or myocardial infarction (MI) surgery. Clustering of >30,000 single cells identified >30 populations representing nine cell lineages, including a previously undescribed fibroblast lineage trajectory present in both sham and MI hearts leading to a uniquely activated cell state defined in part by a strong anti-WNT transcriptome signature. We also uncovered novel myofibroblast subtypes expressing either pro-fibrotic or anti-fibrotic signatures. Our data highlight non-linear dynamics in myeloid and fibroblast lineages after cardiac injury, and provide an entry point for deeper analysis of cardiac homeostasis, inflammation, fibrosis, repair and regeneration.

Keywords: cell biology; computational biology; heart; mouse; myocardial infarction; scRNA-seq; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication
  • Cell Lineage*
  • Disease Models, Animal
  • Gene Expression Profiling
  • Male
  • Mice
  • Myocardial Infarction / pathology*
  • Regeneration*
  • Single-Cell Analysis
  • Wound Healing*

Associated data

  • GEO/GSE97117
  • GEO/GSE95755