In vivo reprogramming of astrocytes to neurons in the adult central nervous system

来源 :第三届国际神经再生高峰论坛暨第五届脊髓损伤治疗与临床试验国际交流会(INRS2013 & 5th ISCITT) | 被引量 : 0次 | 上传用户:ourl123
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  Injuries to the central nervous system lead to irreversible neuronal loss.Neural regeneration from endogenous cells could be an ideal approach to replenish the lost neurons and repair the damage.Astrogliosis is a hallmark of neural damage.These reactive astrocytes are initially beneficial by restricting damage spread but detrimental for long-term recovery and repair of the injured central nervous system.We examined ways to change the fate of these astrocytes to neurons by in vivo screens in the adult central nervous system.Through multiple genetic lineage-tracing approaches,we show for the first time that the single transcription factor SOX2 is sufficient to reprogram resident mature astrocytes into proliferative neuronal precursors (neuroblasts) in the adult mouse brain or spinal cord.These induced adult neuroblasts (iANBs) persist for months and can be generated even in aged mice.When supplied with neurotrophic factors,such as BDNF and Noggin,or treated with a small molecule (vaiproic acid,VPA),iANBs develop into eiectrophysiologically mature neurons,which functionally integrate into the local neural network.Our results demonstrate that adult astrocytes can be reprogrammed to show remarkable plasticity in vivo,a feature that might have important implications in the regeneration of the central nervous system using endogenous patient-specific glial cells.
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