In vivo glial trans-differentiation for neuronal replacement and functional recovery in central nervous system.

摘要: The adult mammalian central nervous system (CNS) is deficient in intrinsic machineries to replace neurons lost injuries or progressive degeneration. Various types of these constitute neural circuitries wired support vital sensory, motor, and cognitive functions. Based on the pioneer studies cell lineage conversion, one promising strategy convert in vivo glial cells into progenitors directly that can be eventually rewired for functional recovery. We first briefly summarize well-studied regeneration-capable CNS zebrafish, focusing their postinjury spontaneous reprogramming retinal Muller glia (MG). then compare signaling transductions, transcriptional epigenetic regulations zebrafish MGs with counterparts, which perpetuate certain barriers against proliferation neurogenesis thus fail MG-to-progenitor conversion. Next, we discuss emerging evidence from mouse studies, glia-to-neuron conversion could achieved sequential one-step genetic manipulations, such as conversions interneurons, photoreceptors, ganglion (RGCs), well midbrain astrocytes dopaminergic GABAergic neurons. Some showed considerable coverage subtypes newly induced partial reestablishment circuits Importantly, would like point out some crucial technical concerns need addressed convincingly show successful Finally, present challenges future directions field better function