Histone Methylations Define Neural Stem/Progenitor Cell Subtypes in the Mouse Subventricular Zone

Histone Methylations Define Neural Stem/Progenitor Cell Subtypes in the Mouse Subventricular Zone
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组蛋白甲基化定义小鼠脑室下区的神经干/祖细胞亚型

DOI:
10.1007/s12035-019-01777-5
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发表时间:
2019-10
影响因子:
5.1
通讯作者:
Arne
Arne
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Zhichao;Manaf Adeel;Li Yanjiao;Perez Sonia Pena;Suganthan Rajikala;Dahl John Arne;Bjoras Magnar;Klungl;Arne

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神经干/祖细胞(Neural stem/progenitor cells, NSPCs)终生存在于哺乳动物大脑中,并在生理和病理生理刺激下被激活。NPSC的表观遗传重编程代表了一种增强脑损伤后大脑再生内在潜力的新策略。因此,明确NSPCs的表观遗传特征对于开发靶向重编程NSPCs以挽救损伤后神经功能的表观遗传疗法具有重要意义。在这项研究中,我们旨在通过个体组蛋白甲基化来定义NSPCs的不同亚型。我们发现三个组蛋白标记,组蛋白H3赖氨酸4三甲基化(H3K4me3),组蛋白H3赖氨酸27三甲基化(H3K27me3)和组蛋白H3赖氨酸36三甲基化(H3K36me3),可以很好地动态描述神经发育过程中的个体细胞类型。首先,我们发现这三个标记都与小鼠室下区NSPC标记SOX2共染色。然后用CD133、Id1、Mash1和DCX免疫染色确定NSPC亚型。E/B型、B/C型和C/A型细胞H3K27me3、H3K36me3和H3K4me3的表达水平分别较高。我们的研究结果揭示了NSPC亚型明确的组蛋白甲基化,支持表观遗传调控对神经发生和维持NSPC至关重要。
Neural stem/progenitor cells (NSPCs) persist in the mammalian brain throughout life and can be activated in response to the physiological and pathophysiological stimuli. Epigenetic reprogramming of NPSC represents a novel strategy for enhancing the intrinsic potential of the brain to regenerate after brain injury. Therefore, defining the epigenetic features of NSPCs is important for developing epigenetic therapies for targeted reprogramming of NSPCs to rescue neurologic function after injury. In this study, we aimed at defining different subtypes of NSPCs by individual histone methylations. We found the three histone marks, histone H3 lysine 4 trimethylation (H3K4me3), histone H3 lysine 27 trimethylation (H3K27me3), and histone H3 lysine 36 trimethylation (H3K36me3), to nicely and dynamically portray individual cell types during neurodevelopment. First, we found all three marks co-stained with NSPC marker SOX2 in mouse subventricular zone. Then, CD133, Id1, Mash1, and DCX immunostaining were used to define NSPC subtypes. Type E/B, B/C, and C/A cells showed high levels of H3K27me3, H3K36me3, and H3K4me3, respectively. Our results reveal defined histone methylations of NSPC subtypes supporting that epigenetic regulation is critical for neurogenesis and for maintaining NSPCs.
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