Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells
Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells
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DOI：
10.1016/j.stem.2012.07.007
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发表时间：
2012-10-05
期刊：
影响因子：
23.9
通讯作者：
Berninger, Benedikt
中科院分区：
文献类型：
--
作者：
Karow, Marisa;Sanchez, Rodrigo;Berninger, Benedikt
体细胞重编程为神经退行性疾病的细胞治疗提供了新的途径。将神经元重编程转化为治疗的一个主要挑战是，成人大脑中是否含有适合直接体细胞转化的细胞群。本研究表明，表达周细胞特征的成人大脑皮层细胞可以通过逆转录病毒介导的转录因子Sox2和Mash1的共表达被重编程为神经元细胞。这些诱导的神经元细胞获得了重复动作电位放电的能力，并作为其他神经元的突触靶点，表明它们具有整合神经网络的能力。在组织非特异性碱性磷酸酶启动子下表达可诱导的Cre重组酶的小鼠的遗传命运定位证实了重编程细胞的周细胞起源。我们的结果提高了成人大脑内源性细胞功能转化为诱导神经元命运的可能性。
Reprogramming of somatic cells into neurons provides a new approach toward cell-based therapy of neurodegenerative diseases. A major challenge for the translation of neuronal reprogramming into therapy is whether the adult human brain contains cell populations amenable to direct somatic cell conversion. Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1. These induced neuronal cells acquire the ability of repetitive action potential firing and serve as synaptic targets for other neurons, indicating their capability of integrating into neural networks. Genetic fate-mapping in mice expressing an inducible Cre recombinase under the tissue-nonspecific alkaline phosphatase promoter corroborated the pericytic origin of the reprogrammed cells. Our results raise the possibility of functional conversion of endogenous cells in the adult human brain to induced neuronal fates.