Deciphering the spatial-temporal transcriptional landscape of human hypothalamus development

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.

Automated summary

This study reveals the cell-type and spatiotemporal characteristics of human hypothalamus development and finds that different cell fates are produced sequentially with spatial developmental asynchrony. Human hypothalamic gliogenesis occurs at an earlier stage compared to mice and shows different transcription profiles. Early oligodendrocyte cells in humans interact with neuronal cells through Wnt, Hippo, and integrin signals to regulate neuronal maturation.