Notch signaling is required to maintain all neural stem cell populations - Irrespective of spatial or temporal niche

Notch signaling is required to maintain all neural stem cell populations - Irrespective of spatial or temporal niche
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DOI:
10.1159/000090751
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发表时间:
2006-01-01
影响因子:
2.9
通讯作者:
van der Kooy, D
van der Kooy, D
中科院分区:
医学3区
文献类型:
--
作者:
Alexson, TO;Hitoshi, S;van der Kooy, D

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最近,Notch信号已被报道强调神经干细胞(NSCs)自我更新的能力。利用早老素-1(PS1)缺陷的小鼠,我们询问Notch信号在NSC维持中的功能是否保守。在胚胎第14.5天,所有的神经干细胞-相似的(皮质-,神经节隆起-和后脑来源的)和不同的(视网膜干细胞)-需要Notch信号以基因剂量敏感的方式进行扩张性对称分裂,如通过克隆,体外神经球测定评估。然而,在成年人中,Notch信号调节细胞周期时间,以确保脑源性NSC保持其自我更新特性。从表面上看,胚胎和成人的影响似乎不同。我们提出了潜在的假设,包括细胞周期的能力,以修改分裂模式,以解决这一矛盾。无论如何,这些发现表明,PS1,可能是Notch信号,是维持所有神经干细胞所必需的。
Recently, Notch signaling has been reported to underscore the ability of neural stem cells (NSCs) to self-renew. Utilizing mice deficient in presenilin-1 (PS1), we asked whether the function of Notch signaling in NSC maintenance was conserved. At embryonic day 14.5, all NSCs - both similar (cortex-, ganglionic eminence- and hindbrain-derived) and distinct (retinal stem cell) - require Notch signaling in a gene-dosage-sensitive manner to undergo expansionary symmetric divisions, as assessed by the clonal, in vitro neurosphere assay. Within the adult, however, Notch signaling modulates cell cycle time in order to ensure brain-derived NSCs retain their self-renewal property. At face value, the effects in the embryo and adult appear different. We propose potential hypotheses, including the ability of cell cycle to modify the mode of division, in order to resolve this discrepancy. Regardless, these findings demonstrate that PS1, and presumably Notch signaling, is required to maintain all NSCs.