Single cell expression analysis reveals anatomical and cell cycle-dependent transcriptional shifts during heart development

Development. 2019 Jun 14;146(12):dev173476. doi: 10.1242/dev.173476.


The heart is a complex organ composed of multiple cell and tissue types. Cardiac cells from different regions of the growing embryonic heart exhibit distinct patterns of gene expression, which are thought to contribute to heart development and morphogenesis. Single cell RNA sequencing allows genome-wide analysis of gene expression at the single cell level. Here, we have analyzed cardiac cells derived from early stage developing hearts by single cell RNA-seq and identified cell cycle gene expression as a major determinant of transcriptional variation. Within cell cycle stage-matched CMs from a given heart chamber, we found that CMs in the G2/M phase downregulated sarcomeric and cytoskeletal markers. We also identified cell location-specific signaling molecules that may influence the proliferation of other nearby cell types. Our data highlight how variations in cell cycle activity selectively promote cardiac chamber growth during development, reveal profound chamber-specific cell cycle-linked transcriptional shifts, and open the way to deeper understanding of pathogenesis of congenital heart disease.

Keywords: Cell cycle; Compact myocardium; Embryonic heart; Ligand receptor interaction; Single cell RNA sequencing; Trabecular myocardium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cluster Analysis
  • Computational Biology
  • Cytoskeleton / metabolism
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental*
  • Genomics
  • Heart / embryology*
  • Mice
  • Morphogenesis
  • Myocardium / metabolism
  • Myocytes, Cardiac / cytology
  • RNA / metabolism
  • Sarcomeres / metabolism
  • Sequence Analysis, RNA
  • Signal Transduction
  • Single-Cell Analysis / methods*
  • Transcription, Genetic*


  • RNA