Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus
Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus
复制标题
发育中的哺乳动物下丘脑神经祖细胞的细胞和分子特性
DOI：
10.1038/s41467-020-17890-2
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发表时间：
2020
影响因子：
16.6
通讯作者：
Xiaoqun Wang
中科院分区：
文献类型：
--
作者：
Xin Zhou;Suijuan Zhong;Honghai Peng;Jing Liu;Wenyu Ding;Le Sun;Qiang Ma;Zeyuan Liu;Ruiguo Chen;Qian Wu;Xiaoqun Wang
神经内分泌下丘脑是重要的生理稳态和行为的中央调节器。然而，下丘脑神经前体细胞的细胞和分子特性仍然未被探索。在这里，下丘脑放射状胶质细胞（hRG）和下丘脑套区放射状胶质细胞（hmRG）细胞被发现是神经祖细胞在发育中的哺乳动物下丘脑。hmRG细胞起源于hRG细胞并产生神经元。在下丘脑的早期发育过程中，神经发生发生在放射柱中，并从hRG细胞开始。放射状胶质纤维朝向下丘脑亚区的位置，其充当神经元迁移的支架。此外，我们使用单细胞RNA测序来揭示人类发育中下丘脑的祖细胞亚型，并表征特定的祖细胞基因，如TTYH 1，HMGA 2和FAM 107 A。我们还证明HMGA2参与E2F1通路，通过靶向下游MYBL 2来调节祖细胞的增殖。不同的神经元亚型在孕10周开始分化并表达下丘脑核的特异性基因。最后，我们揭示了小鼠和人类下丘脑核结构和标记基因的发育保守性。我们对神经前体细胞的细胞和分子特性的鉴定为非层状下丘脑的神经发生和区域形成提供了基本的了解。
The neuroendocrine hypothalamus is the central regulator of vital physiological homeostasis and behavior. However, the cellular and molecular properties of hypothalamic neural progenitors remain unexplored. Here, hypothalamic radial glial (hRG) and hypothalamic mantle zone radial glial (hmRG) cells are found to be neural progenitors in the developing mammalian hypothalamus. The hmRG cells originate from hRG cells and produce neurons. During the early development of hypothalamus, neurogenesis occurs in radial columns and is initiated from hRG cells. The radial glial fibers are oriented toward the locations of hypothalamic subregions which act as a scaffold for neuronal migration. Furthermore, we use single-cell RNA sequencing to reveal progenitor subtypes in human developing hypothalamus and characterize specific progenitor genes, such asTTYH1,HMGA2, andFAM107A. We also demonstrate that HMGA2 is involved in E2F1 pathway, regulating the proliferation of progenitor cells by targeting on the downstream MYBL2. Different neuronal subtypes start to differentiate and express specific genes of hypothalamic nucleus at gestational week 10. Finally, we reveal the developmental conservation of nuclear structures and marker genes in mouse and human hypothalamus. Our identification of cellular and molecular properties of neural progenitors provides a basic understanding of neurogenesis and regional formation of the non-laminated hypothalamus.