A chromatin modulator sustains self-renewal and enables differentiation of postnatal neural stem and progenitor cells.
A chromatin modulator sustains self-renewal and enables differentiation of postnatal neural stem and progenitor cells.
复制标题
染色质调节剂维持自我更新，并使出生后神经干细胞和祖细胞分化。
DOI：
10.1093/jmcb/mjz036
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发表时间：
2020
影响因子：
5.5
通讯作者：
Jiang,Hao
中科院分区：
文献类型：
--
作者：
Shah,Kushani;King,GwendalynD;Jiang,Hao
H3K4甲基化是一种与基因激活相关的表观遗传修饰，它是否调控了出生后神经干细胞和祖细胞（NSPCs）的命运决定仍是未知数。通过灭活小鼠大脑特定区域中主要H3K4甲基转移酶复合物的Dpy30亚基，我们证明了有效的H3K4甲基化在维持出生后NSPCs的自我更新和分化能力方面的关键作用。Dpy 30缺陷破坏海马的发育，特别是齿状回和脑室下区，这是出生后NSC活动的主要区域。DPy30对于以细胞内在方式维持NSPCs的自我更新和增殖是不可或缺的，并且还使得小鼠和人神经祖细胞能够分化为神经元和神经胶质谱系。Dpy30直接调节H3K4甲基化和神经发生中关键的几个基因的诱导。这些发现将基因表达的显著表观遗传机制与NSPCs的基本特性联系起来，并可能对神经发育障碍产生影响。
It remains unknown whether H3K4 methylation, an epigenetic modification associated with gene activation, regulates fate determination of the postnatal neural stem and progenitor cells (NSPCs). By inactivating the Dpy30 subunit of the major H3K4 methyltransferase complexes in specific regions of mouse brain, we demonstrate a crucial role of efficient H3K4 methylation in maintaining both the self-renewal and differentiation capacity of postnatal NSPCs. Dpy30 deficiency disrupts development of hippocampus and especially the dentate gyrus and subventricular zone, the major regions for postnatal NSC activities. Dpy30 is indispensable for sustaining the self-renewal and proliferation of NSPCs in a cell-intrinsic manner and also enables the differentiation of mouse and human neural progenitor cells to neuronal and glial lineages. Dpy30 directly regulates H3K4 methylation and the induction of several genes critical in neurogenesis. These findings link a prominent epigenetic mechanism of gene expression to the fundamental properties of NSPCs and may have implications in neurodevelopmental disorders.