Molecular diversity subdivides the adult forebrain neural stem cell population.

Molecular diversity subdivides the adult forebrain neural stem cell population.
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DOI:
10.1002/stem.1520
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发表时间:
2014-01
期刊:
影响因子:
5.2
通讯作者:
Taylor, Verdon
Taylor, Verdon
中科院分区:
医学2区
文献类型:
--
作者:
Giachino, Claudio;Basak, Onur;Lugert, Sebastian;Knuckles, Philip;Obernier, Kirsten;Fiorelli, Roberto;Frank, Stephan;Raineteau, Olivier;Alvarez-Buylla, Arturo;Taylor, Verdon

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啮齿动物心室下区(V-SVZ)心室区的神经干细胞(NSC)终生产生神经元,而人类的神经干细胞在婴儿期基本上变得不活跃或可能丢失。大多数成体神经干细胞是静止的,表达胶质细胞标记物,并依赖于Notch信号转导进行自我更新和神经元的产生。使用遗传标记和谱系追踪,我们鉴定了成年V-SVZ NSC的亚群(1型、2型和3型),表明包括活化的脑脂质结合蛋白(BLBP、FABP 7)表达干细胞的显著异质性。BLBP+ NSC是侧脑室壁中风车结构的有丝分裂活性组分,并在成年期持续产生神经元。BLBP+神经干细胞表达表皮生长因子(EGF)受体,增殖响应EGF,是SVZ中的主要克隆形成群体。我们还发现BLBP在胎儿和出生后的人脑中由增殖的脑室和脑室下祖细胞表达。BLBP+干/祖细胞的丢失与衰老啮齿动物和出生后人类神经发生减少相关。这些分子异质性和增殖差异的研究结果细分的神经干细胞的人口和哺乳动物在衰老过程中的前脑神经发生的影响。
Neural stem cells (NSCs) in the ventricular domain of the subventricular zone (V-SVZ) of rodents produce neurons throughout life while those in humans become largely inactive or may be lost during infancy. Most adult NSCs are quiescent, express glial markers, and depend on Notch signaling for their self-renewal and the generation of neurons. Using genetic markers and lineage tracing, we identified subpopulations of adult V-SVZ NSCs (type 1, 2, and 3) indicating a striking heterogeneity including activated, brain lipid binding protein (BLBP, FABP7) expressing stem cells. BLBP+ NSCs are mitotically active components of pinwheel structures in the lateral ventricle walls and persistently generate neurons in adulthood. BLBP+ NSCs express epidermal growth factor (EGF) receptor, proliferate in response to EGF, and are a major clonogenic population in the SVZ. We also find BLBP expressed by proliferative ventricular and sub-ventricular progenitors in the fetal and postnatal human brain. Loss of BLBP+ stem/progenitor cells correlates with reduced neurogenesis in aging rodents and postnatal humans. These findings of molecular heterogeneity and proliferative differences subdivide the NSC population and have implications for neurogenesis in the forebrain of mammals during aging.
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