APJ+ cells in the SHF contribute to the cells of aorta and pulmonary trunk through APJ signaling

Dev Biol. 2023 Jun:498:77-86. doi: 10.1016/j.ydbio.2023.04.003. Epub 2023 Apr 8.

Abstract

Outflow tract (OFT) develops from cardiac progenitor cells in the second heart field (SHF) domain. APJ, a G-Protein Coupled Receptor, is expressed by cardiac progenitors in the SHF. By lineage tracing APJ+SHF cells, we show that these cardiac progenitors contribute to the cells of OFT, which eventually give rise to aorta and pulmonary trunk/artery upon its morphogenesis. Furthermore, we show that early APJ ​+ ​cells give rise to both aorta and pulmonary cells but late APJ ​+ ​cells predominantly give rise to pulmonary cells. APJ is expressed by the outflow tract progenitors in the SHF but its role is unclear. We performed knockout studies to determine the role of APJ in SHF cell proliferation and survival. Our data suggested that APJ knockout in the SHF reduced the proliferation of SHF progenitors, while there was no significant impact on survival. In addition, we show that ectopic overexpression of WNT in these cells disrupted aorta and pulmonary morphogenesis from OFT. Overall, our study has identified APJ ​+ ​progenitor population within the SHF that give rise to aorta and pulmonary trunk/artery cells. Furthermore, we show that APJ signaling stimulates proliferation of these cells in the SHF.

Keywords: APJ signaling; Outflow tract development; Second heart field (SHF); WNT signaling.

Publication types

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

MeSH terms

  • Aorta
  • Gene Expression Regulation, Developmental
  • Heart*
  • Myocardium
  • Pulmonary Artery
  • Signal Transduction*
  • Stem Cells