Lineage analysis of quiescent regenerative stem cells in the adult brain by genetic labelling reveals spatially restricted neurogenic niches in the olfactory bulb

Lineage analysis of quiescent regenerative stem cells in the adult brain by genetic labelling reveals spatially restricted neurogenic niches in the olfactory bulb
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DOI:
10.1111/j.1460-9568.2009.06798.x
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发表时间:
2009-07-01
影响因子:
3.4
通讯作者:
Taylor, Verdon
Taylor, Verdon
中科院分区:
医学3区
文献类型:
--
作者:
Giachino, Claudio;Taylor, Verdon

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侧脑室的脑室下区(SVZ)是成年哺乳动物脑内主要的神经发生区,在特定的龛位内藏有神经干细胞。这些干细胞的身份和调节其命运的因素知之甚少。我们已经在出生后发育过程中对表达Nestin的细胞群体进行了遗传作图,以研究它们在体内的潜力和命运。利用巢蛋白::CreER(T2)等位基因的重组特征,我们跟踪了神经干细胞的亚群,并在很大程度上未结合的神经原性生态位中追踪了它们的命运。围产期巢蛋白::CreER(T2)表达细胞产生多种胶质细胞类型和神经元,以及成人SVZ的干细胞。在成人SVZ巢蛋白::CreER(T2)表达神经干细胞在嗅球(OB)中产生几种神经元亚型。我们探讨了是否相同的神经干细胞群在SVZ再生中发挥作用。在抗有丝分裂处理以消除快速分裂的祖细胞后,相对静止的巢蛋白::CreER(T2)靶向细胞得以保留并有助于SVZ再生,产生新的增殖前体和成神经细胞。最后,我们已经确定了神经源性祖细胞聚集在室管膜样壁龛内的嘴迁移流(RMS)的OB。这些OB-RMS祖细胞产生成神经细胞,其在移植、移植、迁移和分化成颗粒和肾小球神经元后。总之,使用条件谱系追踪,我们已经确定了新生儿细胞是成人SVZ中神经源性和再生神经干细胞的来源,并在OB中占据了一个新的神经源性生态位。
The subventricular zone (SVZ) of the lateral ventricles is the major neurogenic region in the adult mammalian brain, harbouring neural stem cells within defined niches. The identity of these stem cells and the factors regulating their fate are poorly understood. We have genetically mapped a population of Nestin-expressing cells during postnatal development to study their potential and fate in vivo. Taking advantage of the recombination characteristics of a nestin::CreER(T2) allele, we followed a subpopulation of neural stem cells and traced their fate in a largely unrecombined neurogenic niche. Perinatal nestin::CreER(T2)-expressing cells give rise to multiple glial cell types and neurons, as well as to stem cells of the adult SVZ. In the adult SVZ nestin::CreER(T2)-expressing neural stem cells give rise to several neuronal subtypes in the olfactory bulb (OB). We addressed whether the same population of neural stem cells play a role in SVZ regeneration. Following anti-mitotic treatment to eliminate rapidly dividing progenitors, relatively quiescent nestin::CreER(T2)-targeted cells are spared and contribute to SVZ regeneration, generating new proliferating precursors and neuroblasts. Finally, we have identified neurogenic progenitors clustered in ependymal-like niches within the rostral migratory stream (RMS) of the OB. These OB-RMS progenitors generate neuroblasts that, upon transplantation, graft, migrate and differentiate into granule and glomerular neurons. In summary, using conditional lineage tracing we have identified neonatal cells that are the source of neurogenic and regenerative neural stem cells in the adult SVZ and occupy a novel neurogenic niche in the OB.