Details

Autor(en) / Beteiligte

• Qian, Cheng
• Dong, Bryan
• Wang, Xu‐Yang
• Zhou, Feng‐Quan

Titel

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

Ist Teil von

• The FEBS journal, 2021-08, Vol.288 (16), p.4773-4785

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 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 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. Distinct from mammalians, zebrafish self‐repair retinas with spontaneous glia‐to‐neuron reprogramming through neural progenitor‐like state. Some recent studies in mouse reported in vivo direct trans‐differentiation for neuronal replacement achieved with genetic manipulations. During such progressively transcriptomic and morphological transitions, single‐cell sequencing‐based lineage trajectory analysis, visualizing the generation and migration of new neurons, and tracing axonal rewiring will serve as additional criteria to convince the successful bona fide glia‐to‐neuron trans‐differentiation.