A cellular atlas ofPitx2-dependent cardiac development

The gene encodes a homeobox transcription factor that is required for mammalian development. Disruption of expression in humans causes congenital heart diseases and is associated with atrial fibrillation; however, the cellular and molecular processes dictated by during cardiac ontogeny remain unclear. To characterize the role of during murine heart development we sequenced over 75,000 single cardiac cell transcriptomes between two key developmental timepoints in control and null embryos. We found that cardiac cell composition was dramatically altered in mutants at both E10.5 and E13.5. Interestingly, the differentiation dynamics of both anterior and posterior second heart field-derived progenitor cells were disrupted in mutants. We also uncovered evidence for defects in left-right asymmetry within atrial cardiomyocyte populations. Furthermore, we were able to detail defects in cardiac outflow tract and valve development associated with Our findings offer insight into function and provide a compilation of gene expression signatures for further detailing the complexities of heart development that will serve as the foundation for future studies of cardiac morphogenesis, congenital heart disease and arrhythmogenesis.