Selective Induction of Human Autonomic Neurons Enables Precise Control of Cardiomyocyte Beating
Selective Induction of Human Autonomic Neurons Enables Precise Control of Cardiomyocyte Beating
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人类自主神经元的选择性诱导能够精确控制心肌细胞的跳动
DOI：
10.1038/s41598-020-66303-3
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发表时间：
2020
影响因子：
4.6
通讯作者：
Kida Yasuyuki S.
中科院分区：
文献类型：
--
作者：
Takayama Yuzo;Kushige Hiroko;Akagi Yuka;Suzuki Yutaka;Kumagai Yutaro;Kida Yasuyuki S.
自主神经系统（ANS）通过去甲肾上腺素能交感神经和胆碱能副交感神经信号的拮抗作用调节组织稳态和重塑。尽管有许多关于从人多能干细胞（hPSC）诱导交感神经元的报道，但没有诱导方法有效地从hPSC衍生出胆碱能副交感神经元。考虑到去甲肾上腺素能和胆碱能输入对靶器官的拮抗作用，预期交感神经元和副交感神经元都被诱导。本研究旨在建立一种化学诱导的方法来诱导交感神经样和副交感神经样ANS神经元。通过限制诱导感觉或肠神经发生的信号和激活骨形态发生蛋白（BMP）信号来实现自主性特化。逐步诱导后的全局mRNA表达分析，包括诱导神经元的单细胞RNA-seq分析和功能测定，揭示了每个诱导的交感神经样或副交感神经样神经元获得具有不同标志物表达的药理学和电生理学功能特性。此外，我们确定了选择性诱导方法，使用适当的接种细胞密度和神经营养因子浓度。单独诱导神经元，促进以拮抗方式调节hiPSC衍生的心肌细胞的搏动速率。诱导方法产生特定的神经元类型，并且它们对各种组织的影响可以通过共培养测定来研究。
The autonomic nervous system (ANS) regulates tissue homeostasis and remodelling through antagonistic effects of noradrenergic sympathetic and cholinergic parasympathetic signalling. Despite numerous reports on the induction of sympathetic neurons from human pluripotent stem cells (hPSCs), no induction methods have effectively derived cholinergic parasympathetic neurons from hPSCs. Considering the antagonistic effects of noradrenergic and cholinergic inputs on target organs, both sympathetic and parasympathetic neurons are expected to be induced. This study aimed to develop a stepwise chemical induction method to induce sympathetic-like and parasympathetic-like ANS neurons. Autonomic specification was achieved through restricting signals inducing sensory or enteric neurogenesis and activating bone morphogenetic protein (BMP) signals. Global mRNA expression analyses after stepwise induction, including single-cell RNA-seq analysis of induced neurons and functional assays revealed that each induced sympathetic-like or parasympathetic-like neuron acquired pharmacological and electrophysiological functional properties with distinct marker expression. Further, we identified selective induction methods using appropriate seeding cell densities and neurotrophic factor concentrations. Neurons were individually induced, facilitating the regulation of the beating rates of hiPSC-derived cardiomyocytes in an antagonistic manner. The induction methods yield specific neuron types, and their influence on various tissues can be studied by co-cultured assays.
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影响因子：
8.8
作者：
Borden P;Houtz J;Leach SD;Kuruvilla R
通讯作者：
Kuruvilla R
DOI：
10.1126/science.aaf2729
发表时间：
2016-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Simoes-Costa M;Bronner ME
通讯作者：
Bronner ME
睫状神经营养因子（CNTF）和去极化对培养交感神经元神经肽表达的影响。
影响因子：
2.7
作者：
Rao,MS;Tyrrell,S;Landis,SC;Patterson,PH
通讯作者：
Patterson,PH
影响因子：
5.2
作者：
Schnerch, Angelique;Cerdan, Chantal;Bhatia, Mickie
通讯作者：
Bhatia, Mickie
影响因子：
4.6
作者：
Müller, F;Rohrer, H
通讯作者：
Rohrer, H