小柯机器人

新方法揭示成年小鼠海马体中长期自我更新的干细胞
2020-12-22 22:03

瑞士苏黎世大学Sebastian Jessberger研究组宣布他们利用活体成像鉴定了成年小鼠海马体中长期自我更新的干细胞。该研究于2020年12月21号发表于国际学术期刊《自然-神经科学》。

通过条件性重组对神经干细胞(NSC)进行基因标记,研究人员利用双光子显微镜追踪了NSC,这些条件性重组受干细胞表达基因GLI家族锌指1(Gli1)或achaete-scute同源物1(Ascl1)调控元件的诱导。通过对NSC及其子细胞进行活体成像,研究人员发现Gli1标记的NSC群体在成年海马中表现出长期自我更新。

相反,Ascl1标记的NSC一旦被激活,在其耗竭前拥有有限的增殖能力。使用单细胞RNA测序,研究人员发现Gli1和Ascl1标记的细胞具有高度相似但截然不同的转录谱,该证据支持了具有不同特性异质NSC群体的存在。总之,该研究揭示了长期自我更新的NSC,它们有助于成年海马中新神经元的产生。

据悉,哺乳动物海马体中的NSC具有终生产生神经元的能力。但是,仍不清楚成年个体大脑中各个NSC长期自我更新的潜能。

附:英文原文

Title: Long-term self-renewing stem cells in the adult mouse hippocampus identified by intravital imaging

Author: Sara Bottes, Baptiste N. Jaeger, Gregor-Alexander Pilz, David J. Jrg, John Darby Cole, Merit Kruse, Lachlan Harris, Vladislav I. Korobeynyk, Izaskun Mallona, Fritjof Helmchen, Franois Guillemot, Benjamin D. Simons, Sebastian Jessberger

Issue&Volume: 2020-12-21

Abstract: Neural stem cells (NSCs) generate neurons throughout life in the mammalian hippocampus. However, the potential for long-term self-renewal of individual NSCs within the adult brain remains unclear. We used two-photon microscopy and followed NSCs that were genetically labeled through conditional recombination driven by the regulatory elements of the stem cell-expressed genes GLI family zinc finger 1 (Gli1) or achaete-scute homolog 1 (Ascl1). Through intravital imaging of NSCs and their progeny, we identify a population of Gli1-targeted NSCs showing long-term self-renewal in the adult hippocampus. In contrast, once activated, Ascl1-targeted NSCs undergo limited proliferative activity before they become exhausted. Using single-cell RNA sequencing, we show that Gli1- and Ascl1-targeted cells have highly similar yet distinct transcriptional profiles, supporting the existence of heterogeneous NSC populations with diverse behavioral properties. Thus, we here identify long-term self-renewing NSCs that contribute to the generation of new neurons in the adult hippocampus. Neurons are generated throughout life in the mammalian hippocampus. Bottes et al. used intravital imaging and comparative single-cell transcriptomics to identify long-term self-renewing neural stem cells in the adult mouse hippocampus.

DOI: 10.1038/s41593-020-00759-4

Source: https://www.nature.com/articles/s41593-020-00759-4

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex


本期文章:《自然—神经科学》:Online/在线发表

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