人类加速区域调节的基因网络涉及到角至基底神经祖先命运过渡的基因网络
bioRxiv : the preprint server for biology
|July 15, 2024
概括
人类加速区域 (HARs) 影响神经干细胞 (NSC) 发育和大脑进化. 这项研究揭示了HARs调节NSC极性,这对人类大脑扩张至关重要.
科学领域:
- 进化生物学是进化的生物学.
- 神经科学是一个神经科学.
- 发育生物学是发展生物学.
背景情况:
- 人类大脑的进化涉及神经干细胞 (NSC) 的变化.
- 人类加速区域 (HARs) 显示出人类特异性的变化,与大脑进化有关.
- 哈尔可以作为神经发育增强剂,但它们在人类NSC中的作用尚未研究.
研究的目的:
- 研究HARs在人类诱导多能干细胞衍生神经干细胞 (iPSC-NSCs) 中的生物功能.
- 评估HARs对NSC生物学和皮质发育的影响.
- 为了确定参与人类大脑扩张的特定HAR.
主要方法:
- 一个直接捕捉的Perturb-seq屏幕被用来抑制iPSC-NSC中的180个神经发育活跃的HARs.
- 对超过188,000个NSC进行了单细胞转录分析.
- 分析了融合的转录效应和基因网络失调.
主要成果:
- 哈尔扰动汇聚在调节NSC基极性的基因网络上.
- 特定的极性调节器 (PARD3,ABI2,SETD2,PCM1) 被HAR扰动失调.
- 抑制HAR181及其标CADM1破坏了顶端PARD3局部化和NSC形形成.
结论:
- 哈尔在NSC生物学和人类皮质发育中发挥着相互关联的作用.
- 特定的HAR与参与人类大脑皮层扩张的过程有关.
- 哈斯调节NSC基极性,这是产生人类扩大的祖先种群的关键过程.
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