Smooth muscle origin of postnatal 2nd CVP is pre-determined in early embryo.

Smooth muscle origin of postnatal 2nd CVP is pre-determined in early embryo.
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DOI:
10.1016/j.bbrc.2016.02.062
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发表时间:
2016-03-18
影响因子:
3.1
通讯作者:
Zhou B
Zhou B
中科院分区:
生物学4区
文献类型:
--
作者:
Liu Q;Zhang H;Tian X;He L;Huang X;Tan Z;Yan Y;Evans SM;Wythe JD;Zhou B

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最近对新生儿第二冠状动脉血管群(第二CVP)的鉴定表明,这些血管的一个子集在出生后心脏的心肌内壁中从头形成并成熟。然而,出生后第二CVP中平滑肌细胞(SMC)的起源仍不确定。使用他莫昔芬诱导的Wt1-CreER驱动程序和Rosa26-RFP报告细胞系,我们追踪了心外膜细胞的谱系,以确定它们是否有助于第二CVP的SMC。晚期胚胎和出生后诱导Wt1-CreER活性表明,在这些阶段Wt1标记的心外膜不显着迁移到心肌形成SMC。然而,在胚胎早期(E10.5)接受他莫昔芬治疗后,我们在E17.5时检测到心肌外壁中的Wt1后代(心外膜衍生细胞或EPDCs)。当第二CVP在出生后阶段形成和重构时,这些早期标记的EDPC重新迁移到心肌内壁深处,并在成人心脏中形成第二CVP-SMC。我们的研究结果表明,在出生后的第二个中心静脉压的平滑肌细胞是预先指定为EPDCs从最早波的心外膜细胞迁移。在出生后发育期间,这些驻留的EPDCs动员并促进第二CVP的平滑肌,而不是在后期阶段重新激活和迁移心外膜细胞。
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.
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