TY - JOUR
T1 - Transcriptome analysis of mouse and human sinoatrial node cells reveals a conserved genetic program
AU - van Eif, Vincent W. W.
AU - Stefanovic, Sonia
AU - van Duijvenboden, Karel
AU - Bakker, Martijn
AU - Wakker, Vincent
AU - de Gier-de Vries, Corrie
AU - Zaffran, Stéphane
AU - Verkerk, Arie O.
AU - Boukens, Bas J.
AU - Christoffels, Vincent M.
PY - 2019
Y1 - 2019
N2 - 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 have isolated and characterized the Tbx3+ cells from Tbx3+/Venus knock-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, the disruption of which in mice did not affect heart rhythm. We also obtained the transcriptomes of the sinoatrial node region, including pacemaker and other cell types, and right atrium of human fetuses, and found a gene program including TBX3, SHOX2, ISL1 and HOX family members, and BMP and NOTCH signaling components conserved between human and mouse. We conclude that a conserved gene program characterizes the sinoatrial node region and that the Tbx3+/Venus allele provides a reliable tool for visualizing the sinoatrial node, and studying its development and function.
AB - 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 have isolated and characterized the Tbx3+ cells from Tbx3+/Venus knock-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, the disruption of which in mice did not affect heart rhythm. We also obtained the transcriptomes of the sinoatrial node region, including pacemaker and other cell types, and right atrium of human fetuses, and found a gene program including TBX3, SHOX2, ISL1 and HOX family members, and BMP and NOTCH signaling components conserved between human and mouse. We conclude that a conserved gene program characterizes the sinoatrial node region and that the Tbx3+/Venus allele provides a reliable tool for visualizing the sinoatrial node, and studying its development and function.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85065346871&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30936179
U2 - https://doi.org/10.1242/dev.173161
DO - https://doi.org/10.1242/dev.173161
M3 - Article
C2 - 30936179
SN - 0950-1991
VL - 146
JO - Development (Cambridge, England)
JF - Development (Cambridge, England)
IS - 8
ER -