Zhou Xin, Lu Yufeng, Zhao Fangqi, Dong Ji, Ma Wenji, Zhong Suijuan, Wang Mengdi, Wang Bosong, Zhao Yuqing, Shi Yingchao, Ma Qiang, Lu Tian, Zhang Jun, Wang Xiaoqun, Wu Qian
State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China.
State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Cell Stem Cell. 2022 Feb 3;29(2):328-343.e5. doi: 10.1016/j.stem.2021.11.009. Epub 2021 Dec 7.
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.
下丘脑由各种核团和神经元亚群组成，它们控制着基本的体内平衡和行为。然而，人类下丘脑发育的时空分子特征在很大程度上尚未得到探索。在此，我们揭示了人类下丘脑发育的时空转录组图谱和细胞类型特征，并阐明了神经祖细胞的分子多样性以及由转录因子组合编程的细胞命运决定。不同的神经元和胶质细胞命运依次产生，并表现出空间发育异步性。此外，人类下丘脑神经胶质生成发生在妊娠早期，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，并通过Wnt、Hippo和整合素信号与神经元细胞相互作用以调节神经元成熟。总体而言，我们的研究提供了人类胚胎早期和中期下丘脑发育的全面分子图景，并为理解其空间和功能复杂性奠定了基础。
