Foxa2 identifies a cardiac progenitor population with ventricular differentiation potential

Nat Commun. 2017 Feb 14;8:14428. doi: 10.1038/ncomms14428.

Abstract

The recent identification of progenitor populations that contribute to the developing heart in a distinct spatial and temporal manner has fundamentally improved our understanding of cardiac development. However, the mechanisms that direct atrial versus ventricular specification remain largely unknown. Here we report the identification of a progenitor population that gives rise primarily to cardiovascular cells of the ventricles and only to few atrial cells (<5%) of the differentiated heart. These progenitors are specified during gastrulation, when they transiently express Foxa2, a gene not previously implicated in cardiac development. Importantly, Foxa2+ cells contribute to previously identified progenitor populations in a defined pattern and ratio. Lastly, we describe an analogous Foxa2+ population during differentiation of embryonic stem cells. Together, these findings provide insight into the developmental origin of ventricular and atrial cells, and may lead to the establishment of new strategies for generating chamber-specific cell types from pluripotent stem cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Line
  • Embryonic Development / physiology
  • Female
  • Gastrulation / physiology
  • Gene Expression Regulation, Developmental
  • Heart Atria / cytology
  • Heart Atria / diagnostic imaging
  • Heart Atria / growth & development
  • Heart Atria / metabolism
  • Heart Ventricles / cytology*
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / growth & development*
  • Hepatocyte Nuclear Factor 3-beta / genetics
  • Hepatocyte Nuclear Factor 3-beta / metabolism*
  • Mesoderm / cytology
  • Mesoderm / growth & development
  • Mesoderm / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism

Substances

  • Foxa2 protein, mouse
  • Hepatocyte Nuclear Factor 3-beta