Liu Qiaozhen, Zhang Hui, Tian Xueying, He Lingjuan, Huang Xiuzhen, Tan Zhen, Yan Yan, Evans Sylvia M, Wythe Joshua D, Zhou Bin
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Department of Pediatric Hematology/Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 200092, China.
Biochem Biophys Res Commun. 2016 Mar 18;471(4):430-6. doi: 10.1016/j.bbrc.2016.02.062. Epub 2016 Feb 18.
Recent identification of the neonatal 2nd coronary vascular population (2nd CVP) suggests that a subset of these vessels form de novo and mature in the inner myocardial wall of the postnatal heart. However, the origin of smooth muscle cells (SMCs) in the postnatal 2nd CVP remains undetermined. Using a tamoxifen-inducible Wt1-CreER driver and a Rosa26-RFP reporter line, we traced the lineage of epicardial cells to determine if they contribute to SMCs of the 2nd CVP. Late embryonic and postnatal induction of Wt1-CreER activity demonstrated that at these stages Wt1-labeled epicardium does not significantly migrate into the myocardium to form SMCs. However, following tamoxifen treatment at an early embryonic stage (E10.5), we detected Wt1 descendants (epicardium-derived cells, or EPDCs) in the outer myocardial wall at E17.5. When the 2nd CVP forms and remodels at postnatal stage, these early labeled EDPCs re-migrate deep into the inner myocardial wall and contribute to 2nd CVP-SMCs in the adult heart. Our findings reveal that SMCs in the postnatal 2nd CVP are pre-specified as EPDCs from the earliest wave of epicardial cell migration. Rather than the re-activation and migration of epicardial cells at later stages, these resident EPDCs mobilize and contribute to smooth muscle of the 2nd CVP during postnatal development.
最近对新生儿第二冠状血管群（2nd CVP）的鉴定表明，这些血管的一个亚群在出生后心脏的心肌内壁中重新形成并成熟。然而，出生后2nd CVP中平滑肌细胞（SMC）的起源仍未确定。我们使用他莫昔芬诱导的Wt1-CreER驱动子和Rosa26-RFP报告基因系，追踪心外膜细胞的谱系，以确定它们是否对2nd CVP的SMC有贡献。Wt1-CreER活性的晚期胚胎和出生后诱导表明，在这些阶段，Wt1标记的心外膜不会显著迁移到心肌中形成SMC。然而，在胚胎早期阶段（E10.5）进行他莫昔芬处理后，我们在E17.5时在外心肌壁中检测到Wt1后代（心外膜衍生细胞，或EPDC）。当2nd CVP在出生后阶段形成并重塑时，这些早期标记的EDPC会重新迁移到心肌内壁深处，并对成年心脏中的2nd CVP-SMC有贡献。我们的研究结果表明，出生后2nd CVP中的SMC在最早的心外膜细胞迁移浪潮中就预先指定为EPDC。在出生后发育过程中，这些驻留的EPDC不是后期心外膜细胞的重新激活和迁移，而是动员并对2nd CVP的平滑肌有贡献。
