Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4.
Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4.
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DOI：
10.1016/j.devcel.2022.10.007
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发表时间：
2022-11-21
影响因子：
11.8
通讯作者：
Red-Horse, Kristy
中科院分区：
文献类型：
--
作者：
D'Amato, Gaetano;Phansalkar, Ragini;Naftaly, Jeffrey A.;Fan, Xiaochen;Amir, Zhainib A.;Coronado, Pamela E. Rios;Cowley, Dale O.;Quinn, Kelsey E.;Sharma, Bikram;Caron, Kathleen M.;Vigilante, Alessandra;Red-Horse, Kristy
在胚胎发育过程中，心脏内腔的内皮细胞是冠状血管的祖细胞。在成年人中重新启动这一发育过程可以再生心脏损伤期间失去的血管，但这需要更多的分子机制知识。在这里，我们使用小鼠遗传学和scRNAseq来鉴定内皮细胞血管生成的调节因子，并精确评估CXCL 12/CXCR 4信号转导的作用。特定时间谱系追踪表明，心内膜细胞主要在妊娠中期分化为冠状动脉内皮细胞。一种新的小鼠品系报告CXCR 4活性-以及细胞特异性基因缺失-证明它是动脉形态发生而不是血管生成所需的。整合来自妊娠中期和晚期的心内膜来源的冠状动脉血管的scRNAseq数据确定了特定于妊娠中期的Bmp 2表达过渡群体。bmp 2在体外和损伤的新生小鼠心脏中刺激内皮细胞血管生成。我们的数据表明，了解血管内皮细胞血管生成的分子机制，可以确定新的潜在的治疗靶点，促进受损心脏的血运重建。确定冠状血管如何从其祖细胞发育而来，可以激发促进缺乏血流的患病心脏血运重建的疗法。D 'Amato等人表明，Bmp 2刺激胚胎心脏中内皮细胞的冠状血管发育，出生后的强制Bmp 2表达重新激活损伤的新生儿心脏中的心内膜衍生的血管形成。
Endocardial cells lining the heart lumen are coronary vessel progenitors during embryogenesis. Reigniting this developmental process in adults could regenerate blood vessels lost during cardiac injury, but this requires additional knowledge on molecular mechanisms. Here, we use mouse genetics and scRNAseq to identify regulators of endocardial angiogenesis and precisely assess the role of CXCL12/CXCR4 signaling. Time-specific lineage tracing demonstrated that endocardial cells differentiated in coronary endothelial cells primarily at mid-gestation. A new mouse line reporting CXCR4 activity—along with cell-specific gene deletions—demonstrated it was specifically required for artery morphogenesis rather than angiogenesis. Integrating scRNAseq data of endocardial-derived coronary vessels from mid- and late-gestation identified a Bmp2-expressing transitioning population specific to mid-gestation. Bmp2 stimulated endocardial angiogenesis in vitro and in injured neonatal mouse hearts. Our data demonstrate how understanding the molecular mechanisms underlying endocardial angiogenesis can identify new potential therapeutic targets promoting revascularization of the injured heart. Identifying how coronary blood vessels develop from their progenitors could inspire therapies promoting revascularization of diseased hearts deprived of blood flow. D’Amato et al. show that Bmp2 stimulates coronary vessel development from endocardial cells in embryonic hearts and forced Bmp2 expression after birth reactivates endocardial-derived vascularization in injured neonatal hearts.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
4.6
作者：
Chen, Heidi I.;Sharma, Bikram;Red-Horse, Kristy
通讯作者：
Red-Horse, Kristy
影响因子：
11.8
作者：
Cavallero, Susana;Shen, Hua;Yi, Christopher;Lien, Ching-Ling;Kumar, S. Ram;Sucov, Henry M.
通讯作者：
Sucov, Henry M.
INO80的内皮缺失破坏了冠状动脉生成并引起先天性心脏病。
影响因子：
16.6
作者：
Rhee S;Chung JI;King DA;D'amato G;Paik DT;Duan A;Chang A;Nagelberg D;Sharma B;Jeong Y;Diehn M;Wu JC;Morrison AJ;Red-Horse K
通讯作者：
Red-Horse K
影响因子：
4.6
作者：
Ehling, Manuel;Adams, Susanne;Adams, Ralf H.
通讯作者：
Adams, Ralf H.