Deciphering the spatial-temporal transcriptional landscape of human hypothalamus development

• Published in: Cell stem cell Vol. 29; no. 2; pp. 328 - 343.e5
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.02.2022
• Subjects: Animals; glial-neuron interaction; gliogenesis; human hypothalamus; Humans; Hypothalamus; Mice; neural progenitor; neuroepithelium; neurogenesis; Neurogenesis - genetics; Neuroglia; Neurons - physiology; Oligodendroglia; scRNA-seq; spatiotemporal regulon; gliogenesis; neuroepithelium; scRNA-seq; human hypothalamus; spatiotemporal regulon; neurogenesis; neural progenitor; glial-neuron interaction
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2021.11.009

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. [Display omitted] •NP fates are hierarchically determined by a combination of transcription factors•Neuron subtypes of different nuclei emerge temporally with distinct gene expression•Glial cells of human hypothalamus are developed with spatial asynchrony•Hypothalamic glial cell development shows species differences in timing and genes Zhou et al. illustrate spatiotemporal transcriptional characteristics of cell types and their differentiation lineage in developing human hypothalamus. They reveal neural progenitor heterogeneity, spatiotemporal asynchrony of cell-type emergence, the transcriptional programs in regulating cell-fate decision, and species difference of gliogenesis in human hypothalamus development.