Origin and progeny of reactive gliosis:: A source of multipotent cells in the injured brain
Origin and progeny of reactive gliosis:: A source of multipotent cells in the injured brain
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DOI：
10.1073/pnas.0709002105
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发表时间：
2008-03-04
影响因子：
11.1
通讯作者：
Goetz, Magdalena
中科院分区：
文献类型：
--
作者：
Buffo, Annalisa;Rite, Inmaculada;Goetz, Magdalena
反应性胶质增生是脑损伤的普遍反应，但对损伤反应的胶质细胞的确切起源和随后的命运尚不清楚。星形胶质细胞通过肥大和胶质细胞酸性蛋白（GFAP）的上调对损伤作出反应。而成熟的星形胶质细胞通常不分裂，反应性GFAP（+）细胞的亚群这样做，提示问题是否增殖GFAP（+）细胞来自内源性胶质祖细胞或成熟的星形胶质细胞开始增殖，以响应脑损伤。在这里，我们通过遗传命运定位和细胞类型特异性病毒靶向显示，静止的星形胶质细胞在刺伤损伤后开始增殖，并有助于反应性胶质细胞增生和GFAP（+）细胞增殖。这些增殖的星形胶质细胞在体内保持其谱系，而在体外更有利的环境显示其多能性和自我更新的能力。相反，存在于成年小鼠大脑皮层中的由NG2或血小板衍生生长因子受体（PDGFR α）标记的祖细胞在脑损伤后（或之前）没有形成神经球。总之，成年小鼠大脑皮层中星形胶质细胞的第一次命运映射分析表明，一些星形胶质细胞在损伤后获得干细胞特性，因此可能提供一种有前途的细胞类型，以启动脑损伤后的修复。
Reactive gliosis is the universal reaction to brain injury, but the precise origin and subsequent fate of the glial cells reacting to injury are unknown. Astrocytes react to injury by hypertrophy and up-regulation of the glial-fibrillary acidic protein (GFAP). Whereas mature astrocytes do not normally divide, a subpopulation of the reactive GFAP(+) cells does so, prompting the question of whether the proliferating GFAP(+) cells arise from endogenous glial progenitors or from mature astrocytes that start to proliferate in response to brain injury. Here we show by genetic fate mapping and cell type-specific viral targeting that quiescent astrocytes start to proliferate after stab wound injury and contribute to the reactive gliosis and proliferating GFAP(+) cells. These proliferating astrocytes remain within their lineage in vivo, while a more favorable environment in vitro revealed their multipotency and capacity for self-renewal. Conversely, progenitors present in the adult mouse cerebral cortex labeled by NG2 or the receptor for the platelet-derived growth factor (PDGFR alpha) did not form neurospheres after (or before) brain injury. Taken together, the first fate-mapping analysis of astrocytes in the adult mouse cerebral cortex shows that some astrocytes acquire stem cell properties after injury and hence may provide a promising cell type to initiate repair after brain injury.