In vivo glial trans-differentiation for neuronal replacement and functional recovery in central nervous system.
In vivo glial trans-differentiation for neuronal replacement and functional recovery in central nervous system.
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DOI：
10.1111/febs.15681
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Zhou FQ
中科院分区：
文献类型：
--
作者：
Qian C;Dong B;Wang XY;Zhou FQ
成年哺乳动物中枢神经系统（CNS）缺乏内在机制来取代损伤或进行性变性中丢失的神经元。各种类型的这些神经元构成神经回路，以支持重要的感觉、运动和认知功能。基于细胞谱系转化的先驱研究，一种有前途的策略是将体内胶质细胞转化为神经祖细胞或直接转化为最终可以重新连接以用于功能恢复的神经元。我们首先简要地总结了充分研究再生能力的斑马鱼中枢神经系统，专注于他们的视网膜Müller胶质细胞（MG）损伤后自发重编程。然后，我们比较了信号转导，转录和表观遗传调控在斑马鱼MG与他们的哺乳动物同行，这永久化某些障碍，对增殖和神经发生，从而在MG祖细胞转换失败。接下来，我们讨论了来自小鼠研究的新证据，其中可以通过顺序或一步遗传操作实现体内胶质细胞到神经元的转换，例如从视网膜MG到中间神经元，光感受器或视网膜神经节细胞（RGC）的转换，以及从中脑星形胶质细胞到多巴胺能或GABA能神经元的转换。其中一些体内研究显示，在新诱导的神经元中有相当多的亚型，神经回路和功能也有部分重建。重要的是，我们想指出一些关键的技术问题，需要解决令人信服地显示成功的胶质细胞到神经元的转换。最后，我们提出了更好的神经功能恢复领域的挑战和未来方向。
The adult mammalian central nervous system (CNS) is deficient in intrinsic machineries to replace neurons lost in injuries or progressive degeneration. Various types of these neurons constitute neural circuitries wired to support vital sensory, motor and cognitive functions. Based on the pioneer studies in cell lineage conversion, one promising strategy is to convert in vivo glial cells into neural progenitors or directly into neurons that can be eventually rewired for functional recovery. We first briefly summarize the well-studied regeneration-capable CNS in the zebrafish, focusing on their post-injury spontaneous reprogramming of the retinal Müller glia (MG). We then compare the signaling transductions, transcriptional and epigenetic regulations in the zebrafish MGs with their mammalian counterparts, which perpetuate certain barriers against proliferation and neurogenesis and thus fail in MG-to-progenitor conversion. Next, we discuss emerging evidence from mouse studies, in which the in vivo glia-to-neuron conversion could be achieved with sequential or one-step genetic manipulations, such as the conversions from retinal MGs to interneurons, photoreceptors or retinal ganglion cells (RGCs), as well as the conversions from midbrain astrocytes to dopaminergic or GABAergic neurons. Some of these in vivo studies showed considerable coverage of subtypes in the newly induced neurons and partial reestablishment in neural circuits and functions. Importantly, we would like to point out some crucial technical concerns that need to be addressed to convincingly show successful glia-to-neuron conversion. Finally, we present challenges and future directions in the field for better neural function recovery.
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影响因子：
64.8
作者：
Pearson, R. A.;Barber, A. C.;Rizzi, M.;Hippert, C.;Xue, T.;West, E. L.;Duran, Y.;Smith, A. J.;Chuang, J. Z.;Azam, S. A.;Luhmann, U. F. O.;Benucci, A.;Sung, C. H.;Bainbridge, J. W.;Carandini, M.;Yau, K. -W.;Sowden, J. C.;Ali, R. R.
通讯作者：
Ali, R. R.
影响因子：
64.8
作者：
Qian H;Kang X;Hu J;Zhang D;Liang Z;Meng F;Zhang X;Xue Y;Maimon R;Dowdy SF;Devaraj NK;Zhou Z;Mobley WC;Cleveland DW;Fu XD
通讯作者：
Fu XD
影响因子：
5.5
作者：
Qian C;Zhou FQ
通讯作者：
Zhou FQ
影响因子：
5.3
作者：
Fausett, Blake V.;Gumerson, Jessica D.;Goldman, Daniel
通讯作者：
Goldman, Daniel
影响因子：
3.4
作者：
Kassen, Sean C.;Thummel, Ryan;Hyde, David R.
通讯作者：
Hyde, David R.