APJ+ cells in the SHF contribute to the cells of aorta and pulmonary trunk through APJ signaling.
APJ+ cells in the SHF contribute to the cells of aorta and pulmonary trunk through APJ signaling.
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DOI：
10.1016/j.ydbio.2023.04.003
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发表时间：
2023-04
影响因子：
2.7
通讯作者：
K. Baral;Gaetano D'Amato;Bryce Kuschel;Frank Bogan;Brendan W. Jones;Colton L. Large;Jeffery D. Whatley;K. Red-Horse;B. Sharma
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文献类型：
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作者：
K. Baral;Gaetano D'Amato;Bryce Kuschel;Frank Bogan;Brendan W. Jones;Colton L. Large;Jeffery D. Whatley;K. Red-Horse;B. Sharma
流出道（OFT）是由第二心野（SHF）区域的心脏祖细胞发育而来。APJ是一种g蛋白偶联受体，在SHF中由心脏祖细胞表达。通过对APJ+SHF细胞的谱系追踪，我们发现这些心脏祖细胞对OFT细胞有贡献，最终在其形态发生时产生主动脉和肺动脉干/动脉。此外，我们发现早期APJ +细胞产生主动脉细胞和肺细胞，但晚期APJ +细胞主要产生肺细胞。APJ在SHF中由流出道祖细胞表达，但其作用尚不清楚。我们进行了基因敲除研究，以确定APJ在SHF细胞增殖和存活中的作用。我们的数据表明，敲除SHF中的APJ可降低SHF祖细胞的增殖，但对生存没有显著影响。此外，我们发现WNT在这些细胞中的异位过表达破坏了OFT的主动脉和肺形态发生。总的来说，我们的研究已经确定了SHF内产生主动脉和肺动脉干/动脉细胞的APJ +祖细胞群。此外，我们发现APJ信号刺激这些细胞在SHF中的增殖。
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.