SOX2 reprograms resident astrocytes into neural progenitors in the adult brain.
SOX2 reprograms resident astrocytes into neural progenitors in the adult brain.
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DOI：
10.1016/j.stemcr.2015.03.006
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发表时间：
2015-05-12
影响因子：
5.9
通讯作者：
Zhang, Chun-Li
中科院分区：
文献类型：
--
作者：
Niu, Wenze;Zang, Tong;Smith, Derek K.;Vue, Tou Yia;Zou, Yuhua;Bachoo, Robert;Johnson, Jane E.;Zhang, Chun-Li
神经胶质细胞可以在体内被重编程为成人中枢神经系统的功能性神经元；然而，这种重编程发生的过程尚不清楚。在这里，我们发现一个不同的细胞序列参与了sox2驱动的成人星形胶质细胞向神经元的原位转化。这包括ASCL1+神经祖细胞和DCX+成体神经母细胞（iANBs）作为中间产物。重要的是，ASCL1对于成年纹状体中ianb的生成是必需的，但不是充分的。当提供神经营养因子或小分子丙戊酸时，这些祖细胞衍生的ianb主要产生calretinin+中间神经元。来自诱导神经元的膜片钳记录显示了亚型异质性，尽管所有神经元都是功能成熟的，发射重复动作电位，并接受突触输入。总之，这些结果表明sox2介导的星形胶质细胞到神经元的体内重编程通过增殖的中间祖细胞进行，这可能被用于再生医学。SOX2在成年小鼠脑内诱导Ascl1阳性神经祖细胞生成成熟的calcalin神经元需要SOX2在常驻星形胶质细胞中介导Ascl1阳性神经祖细胞生成成熟的calcalin神经元。在本文中，Zhang及其同事发现SOX2介导的成人星形胶质细胞体内重编程是通过Ascl1阳性神经祖细胞转运的。这些祖细胞进一步在成年小鼠纹状体中产生dcx阳性的神经母细胞和功能成熟的神经元。这种逐步和可扩展的体内重编程过程可以利用驻留的神经胶质细胞进行神经再生。
Glial cells can be in vivo reprogrammed into functional neurons in the adult CNS; however, the process by which this reprogramming occurs is unclear. Here, we show that a distinct cellular sequence is involved in SOX2-driven in situ conversion of adult astrocytes to neurons. This includes ASCL1+ neural progenitors and DCX+ adult neuroblasts (iANBs) as intermediates. Importantly, ASCL1 is required, but not sufficient, for the robust generation of iANBs in the adult striatum. These progenitor-derived iANBs predominantly give rise to calretinin+ interneurons when supplied with neurotrophic factors or the small-molecule valproic acid. Patch-clamp recordings from the induced neurons reveal subtype heterogeneity, though all are functionally mature, fire repetitive action potentials, and receive synaptic inputs. Together, these results show that SOX2-mediated in vivo reprogramming of astrocytes to neurons passes through proliferative intermediate progenitors, which may be exploited for regenerative medicine. SOX2 induces ASCL1-positive neural progenitors in the adult mouse brain Ascl1 in resident astrocytes is required for SOX2-mediated in vivo reprogramming Induced ASCL1-positive neural progenitors generate mature calretinin neurons In this article, Zhang and colleagues reveal that SOX2-mediated in vivo reprogramming of adult astrocytes transits through ASCL1-positive neural progenitors. These progenitors further generate DCX-positive neuroblasts and functionally mature neurons in the adult mouse striatum. This stepwise and expandable in vivo reprogramming process may be exploited for neural regeneration by using resident glial cells.
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影响因子：
9.8
作者：
Heinrich C;Blum R;Gascón S;Masserdotti G;Tripathi P;Sánchez R;Tiedt S;Schroeder T;Götz M;Berninger B
通讯作者：
Berninger B
影响因子：
64.8
作者：
Abad, Maria;Mosteiro, Lluc;Serrano, Manuel
通讯作者：
Serrano, Manuel
影响因子：
64.5
作者：
Cherry AB;Daley GQ
通讯作者：
Daley GQ
影响因子：
5.7
作者：
Arlotta P;Berninger B
通讯作者：
Berninger B
影响因子：
13.9
作者：
Kriegstein A;Alvarez-Buylla A
通讯作者：
Alvarez-Buylla A