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Dll1 维持成体神经干细胞的静息状态,并在有丝分裂期间进行不对称分裂。

Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis.

机构信息

Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

出版信息

Nat Commun. 2013;4:1880. doi: 10.1038/ncomms2895.

Abstract

Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone. Dll1 protein is induced in activated NSCs and segregates to one daughter cell during mitosis. Dll1-expressing cells reside in close proximity to quiescent NSCs, suggesting a feedback signal for NSC maintenance by their sister cells and progeny. Our data suggest a model in which NSCs produce their own niche cells for their maintenance through asymmetric Dll1 inheritance at mitosis.

摘要

干细胞通常不对称分裂,产生一个干细胞和一个分化细胞,从而维持干细胞池。尽管成年小鼠侧脑室下区的神经干细胞(NSCs)已被证实可以不对称分裂,但不对称 NSC 分裂的内在细胞命运决定因素在很大程度上仍是未知的。干细胞龛对于干细胞的维持很重要,但维持成年静止 NSCs 的龛位仍然不清楚。在这里,我们表明 Notch 配体 Delta-like 1(Dll1)对于维持成年小鼠侧脑室下区的静止 NSCs 是必需的。Dll1 蛋白在激活的 NSCs 中诱导产生,并在有丝分裂过程中分配到一个子细胞中。表达 Dll1 的细胞与静止的 NSCs 紧密相邻,提示通过其姐妹细胞和后代的不对称 Dll1 遗传来维持 NSC 的反馈信号。我们的数据表明,通过有丝分裂中不对称的 Dll1 遗传,NSCs 可以为自身的维持产生龛细胞。

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