<i>In vivo</i> glial trans‐differentiation for neuronal replacement and functional recovery in central nervous system
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- Cheng Qian
- Department of Orthopaedic Surgery The Johns Hopkins University School of Medicine Baltimore MD USA
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- Bryan Dong
- Department of Orthopaedic Surgery The Johns Hopkins University School of Medicine Baltimore MD USA
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- Xu‐Yang Wang
- Department of Orthopaedic Surgery The Johns Hopkins University School of Medicine Baltimore MD USA
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- Feng‐Quan Zhou
- Department of Orthopaedic Surgery The Johns Hopkins University School of Medicine Baltimore MD USA
説明
<jats:p>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 <jats:italic>in vivo</jats:italic> 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 postinjury spontaneous reprogramming of the retinal Müller glia (MG). We then compare the signaling transductions, and 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 <jats:italic>in vivo</jats:italic> 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 <jats:italic>in vivo</jats:italic> 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.</jats:p>
収録刊行物
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- The FEBS Journal
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The FEBS Journal 288 (16), 4773-4785, 2021-01-09
Wiley