GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain
GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain
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DOI：
10.1038/nn1340
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发表时间：
2004-11-01
影响因子：
25
通讯作者：
Sofroniew, MV
中科院分区：
文献类型：
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作者：
Denise, A;Garcia, R;Sofroniew, MV
在体内建立成体多能神经祖细胞的细胞身份是理解其生物学的基础。我们使用了两种转基因策略，以确定相对贡献的胶质细胞酸性蛋白（GFAP）表达祖细胞组成性神经发生在成年前脑。转基因靶向消融成年小鼠室管膜下和颗粒下区的分裂GFAP表达细胞，停止了嗅球和海马齿状回中化学鉴定的神经母细胞和新神经元的产生。转基因靶向细胞的命运映射表明，基本上所有的神经母细胞和神经元新产生的成年小鼠前脑在体内，并在成年多能神经球在体外，来自祖细胞表达GFAP。组成性分裂的GFAP表达祖细胞主要表现为双极或单极形态，与非神经源性多极星形胶质细胞相比，其突起明显减少。这些发现确定了形态学上独特的GFAP表达祖细胞作为组成性成体神经发生的主要来源，并提供了操纵和研究这些细胞的新方法。
Establishing the cellular identity in vivo of adult multipotent neural progenitors is fundamental to understanding their biology. We used two transgenic strategies to determine the relative contribution of glial fibrillary acidic protein (GFAP)-expressing progenitors to constitutive neurogenesis in the adult forebrain. Transgenically targeted ablation of dividing GFAP-expressing cells in the adult mouse subependymal and subgranular zones stopped the generation of immunohistochemically identified neuroblasts and new neurons in the olfactory bulb and the hippocampal dentate gyrus. Transgenically targeted cell fate mapping showed that essentially all neuroblasts and neurons newly generated in the adult mouse forebrain in vivo, and in adult multipotent neurospheres in vitro, derived from progenitors that expressed GFAP. Constitutively dividing GFAP-expressing progenitors showed predominantly bipolar or unipolar morphologies with significantly fewer processes than non-neurogenic multipolar astrocytes. These findings identify morphologically distinctive GFAP-expressing progenitor cells as the predominant sources of constitutive adult neurogenesis, and provide new methods for manipulating and investigating these cells.