Simulated Microgravity Impairs Cardiac Autonomic Neurogenesis from Neural Crest Cells

Simulated Microgravity Impairs Cardiac Autonomic Neurogenesis from Neural Crest Cells
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DOI:
10.1089/scd.2017.0265
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发表时间:
2018-03-20
影响因子:
4
通讯作者:
Hare, Joshua M.
Hare, Joshua M.
中科院分区:
医学3区
文献类型:
--
作者:
Hatzistergos, Konstantinos E.;Jiang, Zhijie;Hare, Joshua M.

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微重力引起的自主神经系统(ANS)变化会导致心血管系统的机械和电生理功能紊乱,导致人类在太空旅行后出现严重症状。由于 ANS 在胚胎时期由神经嵴 (NC) 祖细胞形成,因此我们假设微重力会损害 NC 衍生的心脏结构。因此,我们在具有 cKit(CreERT2/+)、Isl1nLacZ 和 Wnt1-Cre 报告等位基因的小鼠中进行了体外模拟微重力实验,采用 NC 遗传谱系追踪。成年小鼠心脏和多能干细胞 (iPSC) 的诱导命运图谱表明,cKit(CreERT2/+) 介导的 NC 衍生心肌细胞和自主神经元标记减少 (P
Microgravity-induced alterations in the autonomic nervous system (ANS) contribute to derangements in both the mechanical and electrophysiological function of the cardiovascular system, leading to severe symptoms in humans following space travel. Because the ANS forms embryonically from neural crest (NC) progenitors, we hypothesized that microgravity can impair NC-derived cardiac structures. Accordingly, we conducted in vitro simulated microgravity experiments employing NC genetic lineage tracing in mice with cKit(CreERT2/+), Isl1nLacZ, and Wnt1-Cre reporter alleles. Inducible fate mapping in adult mouse hearts and pluripotent stem cells (iPSCs) demonstrated reduced cKit(CreERT2/+)-mediated labeling of both NC-derived cardiomyocytes and autonomic neurons (P