星形胶质细胞可转化为功能性神经细胞

德国慕尼黑大学、亥姆霍兹慕尼黑中心组成的一个研究小组18日宣布在脑细胞再生研究方面取得新进展：使用特殊的转录因子可使大脑皮层的星形胶质细胞转化为功能性神经细胞。这一成果将有助于老年痴呆症或中风等疾病的新疗法研究。

由亥姆霍兹慕尼黑中心干细胞研究所所长玛格达莱娜·格茨领导的这个研究小组在一期美国《公共科学图书馆·生物学》杂志上报告说，通过研究证实，在大脑皮层的星形胶质细胞中植入“Neurogenin2”转录因子可使星形胶质细胞转变为兴奋性神经元，在同样的星形胶质细胞中植入“Dlx2”转录因子则可使其转变为抑制性神经元。

星形胶质细胞是哺乳动物脑内分布zui广泛的一类细胞，其胞体发出的许多长而分支的突起伸展充填在神经细胞的胞体及其突起之间，起支持和分隔神经细胞的作用。德国研究人员指出，星形胶质细胞与放射状胶质细胞密切相关，而后者则是胎胚发育过程中大多数神经元的前驱细胞。

德研究人员进一步解释说，格茨领导的研究小组在几年前的研究中已发现，在幼鼠大脑皮层本来不具有形成神经元能力的星形胶质细胞中植入特殊的调节蛋白，可促使其转变为神经元。而他们的研究则显示，新形成的神经元在特殊转录因子的影响下可进一步形成功能性突触，释放出兴奋性或抑制性的递质。不仅还在发育的星形胶质细胞发生转变，而且因受损而被激活的成熟大脑中的星形胶质细胞也能发生这种转变。这一发现使研究人员相信有望找到用脑中现有的星形胶质细胞“更新”因伤或疾病而受损的脑细胞的方法。

上海劲马生物推荐原文出处：

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.