In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics.
In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics.
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DOI：
10.1016/j.cell.2011.05.024
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发表时间：
2011-06-24
期刊：
影响因子：
64.5
通讯作者：
Song H
中科院分区：
文献类型：
--
作者：
Bonaguidi MA;Wheeler MA;Shapiro JS;Stadel RP;Sun GJ;Ming GL;Song H
在成年哺乳动物大脑的离散区域中，神经发生和神经胶质发生继续。一个基本的问题是细胞起源是来自不同谱系限制的祖细胞还是成人大脑中的自我更新和多能神经干细胞的发生。在这里，我们制定了一种遗传标记策略，用于对成年小鼠齿状回的单个，静止和表达巢蛋白radial神经胶质样（RGL）前体的谱系追踪。克隆分析确定了多种RGL激活模式，包括不对称和对称的自我更新。长期对体内的谱系追踪显示，包含RGL（S），神经元和星形胶质细胞的克隆很大一部分，表明单个RGL的能力用于自我更新和多部位分化。此外，RGL中有条件的PTEN缺失最初会促进其激活和对称的自我更新，但最终导致成人海马的终末星形细胞分化和耗竭。我们的研究将RGL鉴定为自我更新和多能神经干细胞，并为成人神经干细胞的体内特性提供了新的见解。
Neurogenesis and gliogenesis continue in discrete regions of the adult mammalian brain. A fundamental question remains whether cell genesis occurs from distinct lineage-restricted progenitors or from self-renewing and multipotent neural stem cells in the adult brain. Here, we developed a genetic marking strategy for lineage-tracing of individual, quiescent, and nestin-expressing radial glia-like (RGL) precursors in the adult mouse dentate gyrus. Clonal analysis identified multiple modes of RGL activation, including asymmetric and symmetric self-renewal. Long-term lineage-tracing in vivo revealed a significant percentage of clones that contained RGL(s), neurons, and astrocytes, indicating capacity of individual RGLs for both self-renewal and multi-lineage differentiation. Furthermore, conditional Pten deletion in RGLs initially promotes their activation and symmetric self-renewal, but ultimately leads to terminal astrocytic differentiation and depletion in the adult hippocampus. Our study identifies RGLs as self-renewing and multipotent neural stem cells and provides novel insights into in vivo properties of adult neural stem cells.
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影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
DOI：
10.1126/science.1180794
发表时间：
2010-01-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li L;Clevers H
通讯作者：
Clevers H
影响因子：
13.9
作者：
Kriegstein A;Alvarez-Buylla A
通讯作者：
Alvarez-Buylla A
影响因子：
5.3
作者：
Maslov, AY;Barone, TA;Pruitt, SC
通讯作者：
Pruitt, SC
影响因子：
23.9
作者：
Encinas, Juan M.;Michurina, Tatyana V.;Peunova, Natalia;Park, June-Hee;Tordo, Julie;Peterson, Daniel A.;Fishell, Gord;Koulakov, Alex;Enikolopov, Grigori
通讯作者：
Enikolopov, Grigori