Life-Long Neural Stem Cells Are Fate-Specified at an Early Developmental Stage

Life-Long Neural Stem Cells Are Fate-Specified at an Early Developmental Stage
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DOI:
10.1093/cercor/bhaa200
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发表时间:
2020-12-01
期刊:
影响因子:
3.7
通讯作者:
Hitoshi, Seiji
Hitoshi, Seiji
中科院分区:
医学2区
文献类型:
--
作者:
Tanaka, Aoi;Ishida, Shohei;Hitoshi, Seiji

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成年哺乳动物大脑中静止的神经干细胞(NSCs)的起源和终生命运在很大程度上仍不清楚。胚胎脑中的少数神经前体细胞延长了其细胞周期时间,随后在出生后变得静止,这表明有可能在胚胎早期选择了终生神经干细胞。在这里,我们利用一种表达GFP的慢病毒通过鉴定慢病毒整合位点来研究慢病毒感染的个体NSCs后代的命运。我们的数据表明,在小鼠胚胎13.5天之前,神经干细胞被指定为两个或更多的谱系:一个NSC谱系只为皮质产生细胞,另一个谱系为嗅球提供神经元。在成人大脑中,大多数形成神经球的神经干细胞相对处于休眠状态,在嗅球或皮质中产生的细胞很少,如果有的话,这个神经干细胞群体可以作为一个储存库,在以后的生活中偶尔会重新激活。
The origin and life-long fate of quiescent neural stem cells (NSCs) in the adult mammalian brain remain largely unknown. A few neural precursor cells in the embryonic brain elongate their cell cycle time and subsequently become quiescent postnatally, suggesting the possibility that life-long NSCs are selected at an early embryonic stage. Here, we utilized a GFP-expressing lentivirus to investigate the fate of progeny from individual lentivirus-infected NSCs by identifying the lentiviral integration site. Our data suggest that NSCs become specified to two or more lineages prior to embryonic day 13.5 in mice: one NSC lineage produces cells only for the cortex and another provides neurons to the olfactory bulb. The majority of neurosphere-forming NSCs in the adult brain are relatively dormant and generate very few cells, if any, in the olfactory bulb or cortex, and this NSC population could serve as a reservoir that is occasionally reactivated later in life.