Abstract：
The hypothalamus comprises various nuclei and neuronal subpopulations that control fundamental homeostasis and behaviors. However, spatiotemporal molecular characterization of hypothalamus development in humans is largely unexplored. Here, we revealed spatiotemporal transcriptome profiles and cell-type characteristics of human hypothalamus development and illustrated the molecular diversity of neural progenitors and the cell-fate decision, which is programmed by a combination of transcription factors. Different neuronal and glial fates are sequentially produced and showed spatial developmental asynchrony. Moreover, human hypothalamic gliogenesis occurs at an earlier stage of gestation and displays distinctive transcription profiles compared with those in mouse. Notably, early oligodendrocyte cells in humans exhibit different gene patterns and interact with neuronal cells to regulate neuronal maturation by Wnt, Hippo, and integrin signals. Overall, our study provides a comprehensive molecular landscape of human hypothalamus development at early- and mid-embryonic stages and a foundation for understanding its spatial and functional complexity.
摘要：
下丘脑包括控制基本稳态和行为的各种细胞核和神经元亚群。然而,人类下丘脑发育的时空分子特征在很大程度上尚未探索。这里,我们揭示了人类下丘脑发育的时空转录组特征和细胞类型特征，并说明了神经祖细胞的分子多样性和细胞命运决定，由转录因子的组合编程。依次产生不同的神经元和神经胶质命运，并显示出空间发育不同步。此外，人类下丘脑胶质细胞生成发生在妊娠的早期，与小鼠相比，显示出独特的转录谱。值得注意的是,人类早期少突胶质细胞表现出不同的基因模式，并与神经元细胞相互作用，通过Wnt调节神经元成熟，河马,和整合素信号。总的来说,我们的研究提供了人类下丘脑发育早期和中期胚胎阶段的全面分子景观，并为理解其空间和功能复杂性奠定了基础。
