Moving CNS axon growth and regeneration research into human model systems.
Moving CNS axon growth and regeneration research into human model systems.
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DOI：
10.3389/fnins.2023.1198041
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发表时间：
2023
影响因子：
4.3
通讯作者：
Moore, Darcie L.
中科院分区：
文献类型：
--
作者：
Lear, Bo P.;Moore, Darcie L.
由于内在和外在因素，成年哺乳动物中枢神经系统（CNS）的轴突再生受到限制。啮齿动物研究表明，发育年龄可以驱动内在轴突生长能力的差异，例如胚胎啮齿动物CNS神经元延伸长轴突，而出生后和成年CNS神经元则没有。近几十年来，科学家们已经确定了啮齿动物中调节生长的几种内在发育调节因子。然而，中枢神经系统轴突生长的这种发育程序性下降是否在人类中是保守的尚不清楚。直到最近，人类神经元模型系统有限，特定年龄的人类模型甚至更少。人类体外模型的范围从多能干细胞衍生的神经元到直接重编程（转分化）的源自人类体细胞的神经元。在这篇综述中，我们讨论了每个系统的优点和缺点，以及研究人类神经元中的轴突生长如何在CNS轴突再生领域提供物种特异性知识，其目标是将基础科学研究与临床试验联系起来。此外，随着人类皮层组织在发育和寿命期间的组学数据集的可用性和质量的提高，科学家可以挖掘这些数据集以获得发育调节的途径和基因。由于在人类神经元中进行的研究很少，研究轴突生长的调节剂，在这里，我们提供了方法的总结，开始将CNS轴突生长和再生领域转移到人类模型系统中，以发现轴突生长的新驱动因素。
Axon regeneration is limited in the adult mammalian central nervous system (CNS) due to both intrinsic and extrinsic factors. Rodent studies have shown that developmental age can drive differences in intrinsic axon growth ability, such that embryonic rodent CNS neurons extend long axons while postnatal and adult CNS neurons do not. In recent decades, scientists have identified several intrinsic developmental regulators in rodents that modulate growth. However, whether this developmentally programmed decline in CNS axon growth is conserved in humans is not yet known. Until recently, there have been limited human neuronal model systems, and even fewer age-specific human models. Human in vitro models range from pluripotent stem cell-derived neurons to directly reprogrammed (transdifferentiated) neurons derived from human somatic cells. In this review, we discuss the advantages and disadvantages of each system, and how studying axon growth in human neurons can provide species-specific knowledge in the field of CNS axon regeneration with the goal of bridging basic science studies to clinical trials. Additionally, with the increased availability and quality of ‘omics datasets of human cortical tissue across development and lifespan, scientists can mine these datasets for developmentally regulated pathways and genes. As there has been little research performed in human neurons to study modulators of axon growth, here we provide a summary of approaches to begin to shift the field of CNS axon growth and regeneration into human model systems to uncover novel drivers of axon growth.
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影响因子：
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作者：
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影响因子：
23.9
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Ding S
影响因子：
14.9
作者：
Ament, Seth A.;Adkins, Ricky S.;Carter, Robert;Chrysostomou, Elena;Colantuoni, Carlo;Crabtree, Jonathan;Creasy, Heather H.;Degatano, Kylee;Felix, Victor;Gandt, Peter;Garden, Gwenn A.;Giglio, Michelle;Herb, Brian R.;Khajouei, Farzaneh;Kiernan, Elizabeth;McCracken, Carrie;McDaniel, Kennedy;Nadendla, Suvarna;Nickel, Lance;Olley, Dustin;Orvis, Joshua;Receveur, Joseph P.;Schor, Mike;Sonthalia, Shreyash;Tickle, Timothy L.;Way, Jessica;Hertzano, Ronna;Mahurkar, Anup A.;White, Owen R.
通讯作者：
White, Owen R.