Maintenance of neural stem cell positional identity by mixed-lineage leukemia 1.

Maintenance of neural stem cell positional identity by mixed-lineage leukemia 1.
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DOI:
10.1126/science.aba5960
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发表时间:
2020-04-03
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Lim DA
Lim DA
中科院分区:
其他
文献类型:
--
作者:
Delgado RN;Mansky B;Ahanger SH;Lu C;Andersen RE;Dou Y;Alvarez-Buylla A;Lim DA

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发育中和出生后大脑中的神经干细胞(NSC)具有不同的位置特征,决定了它们生成的神经元类型。尽管形态发生素最初在神经管中建立了 NSC 的位置同一性,但目前尚不清楚随着前脑变得更大且解剖结构更复杂,如何维持这种区域差异。我们发现,维持小鼠大脑中 NSC 位置同一性需要混合谱系白血病 1 (Mll1) 依赖的表观遗传记忆系统。在声波刺猬建立后,腹侧 NSC 的身份变得独立于这种形态发生素。即使短暂的 MLL1 抑制也会导致腹侧身份的持久丧失,从而导致体内产生具有背侧 NSC 特征的神经元。因此,形态发生素提供的空间信息可以转化为表观遗传机制,维持前脑区域不同的发育程序。 NSC 中位置同一性的表观遗传记忆。
Neural stem cells (NSCs) in the developing and postnatal brain have distinct positional identities that dictate the types of neurons they generate. Although morphogens initially establish NSC positional identity in the neural tube, it is unclear how such regional differences are maintained as the forebrain grows much larger and more anatomically complex. We found that the maintenance of NSC positional identity in the murine brain requires a mixed-lineage leukemia 1 (Mll1)–dependent epigenetic memory system. After establishment by sonic hedgehog, ventral NSC identity became independent of this morphogen. Even transient MLL1 inhibition caused a durable loss of ventral identity, resulting in the generation of neurons with the characteristics of dorsal NSCs in vivo. Thus, spatial information provided by morphogens can be transitioned to epigenetic mechanisms that maintain regionally distinct developmental programs in the forebrain. Epigenetic memory of positional identity in NSCs.
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