Oligodendrocytes(OLs)are the only myelinforming cells in the central nervous system.Their differentiation from OL precursor cells(OPCs)occurs throughout life and is mediated by numerous intrinsic and extrinsic factors...Oligodendrocytes(OLs)are the only myelinforming cells in the central nervous system.Their differentiation from OL precursor cells(OPCs)occurs throughout life and is mediated by numerous intrinsic and extrinsic factors.OL transcription factor 2(Olig2),a basic helix-loophelix transcription factor,is one of the intrinsic factors that specify the OL lineage.It is expressed by both OPCs and OLs,and no variant of Olig2 has yet been identified in rodents.Although the function of Olig2 in OL maturation and myelination is still under debate.展开更多
Investigating neural stem cell plasticity in the hippo-campal niche, we demonstrate that retroviral forced expression of Mash1 (Mammalian Achaete-Scute Homolog 1), Olig1(Oligodendrocyte transcription factor 1), and Ol...Investigating neural stem cell plasticity in the hippo-campal niche, we demonstrate that retroviral forced expression of Mash1 (Mammalian Achaete-Scute Homolog 1), Olig1(Oligodendrocyte transcription factor 1), and Olig2 (Oligodendrocyte transcription factor 2) genes, transcription factors involved in enhanced oligodendrogenesis, can contribute to directing the differentiation of adult subventricular zone neural stem cells to functional oligodendrocytes. We found that Mash1, Olig1 and Olig2 all induced oligodendrocyte differentiation. However, Olig1 and Olig2 induction resulted in an elevated number of generated oligoden-drocytes without a significant production of other cell lineages, unlike Mash1. These newly differentiated cells are also capable of migration and possible myelination, showing that targeting oligodendrocyte production and possible remyelination is a viable therapeutic strategy for restoration of neuronal function.展开更多
Oligodendrocyte (OL) and myelin development are crucial for network integration and are associated with higher brain functions. Accumulating evidence has demonstrated structural and functional impairment of OLs and my...Oligodendrocyte (OL) and myelin development are crucial for network integration and are associated with higher brain functions. Accumulating evidence has demonstrated structural and functional impairment of OLs and myelin in serious mental illnesses. However, whether these deficits contribute to the brain dysfunction or pathogenesis of such diseases still lacks direct evidence. In this study, we conditionally deleted Olig2 in oligodendroglial lineage cells (Olig2 cKO) and screened the behavioral changes in adult mice. We found that Olig2 ablation impaired myelin development, which further resulted in severe hypomyelination in the anterior cingulate cortex. Strikingly, Olig2 cKO mice exhibited an anxious phenotype, aberrant responses to stress, and cognitive deficits. Moreover, Olig2 cKO mice showed increased vulnerability to social avoidance under the mild stress of social isolation. Together,these results indicate that developmental deficits in OL and myelin lead to cognitive impairment and increase the risk of phenotypes reminiscent of mental illnesses.展开更多
基金a Nano Bio Med Young Investigator grant from the University of Saarland(to XB)。
文摘Oligodendrocytes(OLs)are the only myelinforming cells in the central nervous system.Their differentiation from OL precursor cells(OPCs)occurs throughout life and is mediated by numerous intrinsic and extrinsic factors.OL transcription factor 2(Olig2),a basic helix-loophelix transcription factor,is one of the intrinsic factors that specify the OL lineage.It is expressed by both OPCs and OLs,and no variant of Olig2 has yet been identified in rodents.Although the function of Olig2 in OL maturation and myelination is still under debate.
文摘Investigating neural stem cell plasticity in the hippo-campal niche, we demonstrate that retroviral forced expression of Mash1 (Mammalian Achaete-Scute Homolog 1), Olig1(Oligodendrocyte transcription factor 1), and Olig2 (Oligodendrocyte transcription factor 2) genes, transcription factors involved in enhanced oligodendrogenesis, can contribute to directing the differentiation of adult subventricular zone neural stem cells to functional oligodendrocytes. We found that Mash1, Olig1 and Olig2 all induced oligodendrocyte differentiation. However, Olig1 and Olig2 induction resulted in an elevated number of generated oligoden-drocytes without a significant production of other cell lineages, unlike Mash1. These newly differentiated cells are also capable of migration and possible myelination, showing that targeting oligodendrocyte production and possible remyelination is a viable therapeutic strategy for restoration of neuronal function.
基金supported by the National Natural Science Foundation of China (31671117).
文摘Oligodendrocyte (OL) and myelin development are crucial for network integration and are associated with higher brain functions. Accumulating evidence has demonstrated structural and functional impairment of OLs and myelin in serious mental illnesses. However, whether these deficits contribute to the brain dysfunction or pathogenesis of such diseases still lacks direct evidence. In this study, we conditionally deleted Olig2 in oligodendroglial lineage cells (Olig2 cKO) and screened the behavioral changes in adult mice. We found that Olig2 ablation impaired myelin development, which further resulted in severe hypomyelination in the anterior cingulate cortex. Strikingly, Olig2 cKO mice exhibited an anxious phenotype, aberrant responses to stress, and cognitive deficits. Moreover, Olig2 cKO mice showed increased vulnerability to social avoidance under the mild stress of social isolation. Together,these results indicate that developmental deficits in OL and myelin lead to cognitive impairment and increase the risk of phenotypes reminiscent of mental illnesses.
