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德國慕尼黑大學、亥姆霍茲慕尼黑中心組成的一個研究小組18日宣布在腦細胞再生研究方面取得新進展：使用特殊的轉錄因子可使大腦皮層的星形膠質細胞轉化為功能性神經(jīng)細胞。這一成果將有助于老年癡呆癥或中風等疾病的新療法研究。
由亥姆霍茲慕尼黑中心干細胞研究所所長瑪格達萊娜·格茨領導的這個研究小組在一期美國《公共科學圖書館·生物學》雜志上報告說，通過研究證實，在大腦皮層的星形膠質細胞中植入“Neurogenin2”轉錄因子可使星形膠質細胞轉變?yōu)榕d奮性神經(jīng)元，在同樣的星形膠質細胞中植入“Dlx2”轉錄因子則可使其轉變?yōu)橐种菩陨窠?jīng)元。
星形膠質細胞是哺乳動物腦內分布zui廣泛的一類細胞，其胞體發(fā)出的許多長而分支的突起伸展充填在神經(jīng)細胞的胞體及其突起之間，起支持和分隔神經(jīng)細胞的作用。德國研究人員指出，星形膠質細胞與放射狀膠質細胞密切相關，而后者則是胎胚發(fā)育過程中大多數(shù)神經(jīng)元的前驅細胞。
德研究人員進一步解釋說，格茨領導的研究小組在幾年前的研究中已發(fā)現(xiàn)，在幼鼠大腦皮層本來不具有形成神經(jīng)元能力的星形膠質細胞中植入特殊的調節(jié)蛋白，可促使其轉變?yōu)樯窠?jīng)元。而他們的研究則顯示，新形成的神經(jīng)元在特殊轉錄因子的影響下可進一步形成功能性突觸，釋放出興奮性或抑制性的遞質。不僅還在發(fā)育的星形膠質細胞發(fā)生轉變，而且因受損而被激活的成熟大腦中的星形膠質細胞也能發(fā)生這種轉變。這一發(fā)現(xiàn)使研究人員相信有望找到用腦中現(xiàn)有的星形膠質細胞“更新”因傷或疾病而受損的腦細胞的方法。
上海勁馬生物推薦原文出處：
PLoS Biology doi:10.1371/journal.pbio.1000373
Directing Astroglia from the Cerebral Cortex into Subtype Specific Functional Neurons
Christophe Heinrich1,2, Robert Blum1#¤, Sergio Gascón1,2#, Giacomo Masserdotti1#, Pratibha Tripathi2, Rodrigo Sánchez1, Steffen Tiedt1, Timm Schroeder2, Magdalena G?tz1,2,3?*, Benedikt Berninger1,2?*
Astroglia from the postnatal cerebral cortex can be reprogrammed in vitro to generate neurons following forced expression of neurogenic transcription factors, thus opening new avenues towards a potential use of endogenous astroglia for brain repair. However, in previous attempts astroglia-derived neurons failed to establish functional synapses, a severe limitation towards functional neurogenesis. It remained therefore also unknown whether neurons derived from reprogrammed astroglia could be directed towards distinct neuronal subtype identities by selective expression of distinct neurogenic fate determinants. Here we show that strong and persistent expression of neurogenic fate determinants driven by silencing-resistant retroviral vectors instructs astroglia from the postnatal cortex in vitro to mature into fully functional, synapse-forming neurons. Importantly, the neurotransmitter fate choice of astroglia-derived neurons can be controlled by selective expression of distinct neurogenic transcription factors: forced expression of the dorsal encephalic fate determinant neurogenin-2 （Neurog2） directs cortical astroglia to generate synapse-forming glutamatergic neurons; in contrast, the ventral encephalic fate determinant Dlx2 induces a GABAergic identity, although the overall efficiency of Dlx2-mediated neuronal reprogramming is much lower compared to Neurog2, suggesting that cortical astroglia possess a higher competence to respond to the dorsal encephalic fate determinant. Interestingly, however, reprogramming of astroglia towards the generation of GABAergic neurons was greatly facilitated when the astroglial cells were first expanded as neurosphere cells prior to transduction with Dlx2. Importantly, this approach of expansion under neurosphere conditions and subsequent reprogramming with distinct neurogenic transcription factors can also be extended to reactive astroglia isolated from the adult injured cerebral cortex, allowing for the selective generation of glutamatergic or GABAergic neurons. These data provide evidence that cortical astroglia can undergo a conversion across cell lineages by forced expression of a single neurogenic transcription factor, stably generating fully differentiated neurons. Moreover, neuronal reprogramming of astroglia is not restricted to postnatal stages but can also be achieved from terminally differentiated astroglia of the adult cerebral cortex following injury-induced reactivation.
