Kizil Lab, German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany.
Kizil Lab, German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany.
Cell Rep. 2019 Apr 23;27(4):1307-1318.e3. doi: 10.1016/j.celrep.2019.03.090.
The neural stem cell (NSC) reservoir can be harnessed for stem cell-based regenerative therapies. Zebrafish remarkably regenerate their brain by inducing NSC plasticity in a Amyloid-β-42 (Aβ42)-induced experimental Alzheimer's disease (AD) model. Interleukin-4 (IL-4) is also critical for AD-induced NSC proliferation. However, the mechanisms of this response have remained unknown. Using single-cell transcriptomics in the adult zebrafish brain, we identify distinct subtypes of NSCs and neurons and differentially regulated pathways and their gene ontologies and investigate how cell-cell communication is altered through ligand-receptor pairs in AD conditions. Our results propose the existence of heterogeneous and spatially organized stem cell populations that react distinctly to amyloid toxicity. This resource article provides an extensive database for the molecular basis of NSC plasticity in the AD model of the adult zebrafish brain. Further analyses of stem cell heterogeneity and neuro-regenerative ability at single-cell resolution could yield drug targets for mobilizing NSCs for endogenous neuro-regeneration in humans.
神经干细胞 (NSC) 库可用于基于干细胞的再生疗法。斑马鱼通过在淀粉样蛋白-β 42 (Aβ42) 诱导的实验性阿尔茨海默病 (AD) 模型中诱导 NSC 可塑性，显著地实现了大脑的再生。白细胞介素 4 (IL-4) 对于 AD 诱导的 NSC 增殖也是至关重要的。然而，这种反应的机制仍然未知。我们使用成年斑马鱼大脑中的单细胞转录组学，鉴定了不同的 NSC 和神经元亚型，以及差异调节的途径及其基因本体，并研究了在 AD 条件下细胞间通讯如何通过配体-受体对发生改变。我们的结果提出了存在异质和空间组织的干细胞群体，它们对淀粉样毒性有明显不同的反应。本资源文章为成年斑马鱼大脑 AD 模型中 NSC 可塑性的分子基础提供了一个广泛的数据库。在单细胞分辨率下进一步分析干细胞异质性和神经再生能力，可能会为人类内源性神经再生中动员 NSC 的药物靶点提供信息。
