Transcriptome analysis of mouse and human sinoatrial node cells reveals a conserved genetic program
2019
The rate of contraction of the heart relies on proper development and function of the
sinoatrial node, which consists of a small heterogeneous cell population, including Tbx3 +
pacemaker cells. Here we isolated and characterized the Tbx3 + cells from Tbx3 +/
Venusknock-in mice. We studied electrophysiological parameters during development and found that
Venus-labeled cells are genuine Tbx3 +
pacemaker cells. We analyzed the transcriptomes of late fetal FACS-purified Tbx3 + sinoatrial nodal cells and Nppb-Katushka + atrial and ventricular chamber cardiomyocytes, and identified a
sinoatrial node-enriched gene program including key nodal transcription factors, BMP-signaling, and Smoc2 , which disruption in mice did not affect
heart rhythm. We also obtained the transcriptomes of the
sinoatrial noderegion, including pacemaker and other cell types, and
right atriumof human fetuses, and found a gene program including TBX3 , SHOX2 ,
ISL1, HOX family members, and BMP- and NOTCH-signaling components conserved between human and mouse. We conclude that a conserved gene program characterizes the
sinoatrial noderegion and that the Tbx3 +/
Venusallele provides a reliable tool to visualize the
sinoatrial nodeand to study its development and function.
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