Study reveals spatiotemporal dynamics of human hypothalamic development

The hypothalamus is composed of a variety of neuronal subtypes with different shapes and functions.

In a study published in "Nature Communications" in 2020, Wu Qian's research group from Beijing Normal University and Wang Xiaoqun's research group from the Institute of Biophysics of the Chinese Academy of Sciences collaborated to discover the existence of a new type of neural stem cells in the mammalian hypothalamus-- hmRG cells, a group of cells similar to the lateral radioglial cells in the cortex (oRG cells, precursor cells for neurogenesis in the cerebral cortex), play an important role in hypothalamic development

On December 7, 2021, Wu Qian's research group, Wang Xiaoqun's research group and Zhang Jun's research group of Anzhen Hospital Affiliated to Capital Medical University, in a study published in the journal Cell Stem Cell, systematically revealed the human hypothalamus in embryonic development.

Based on the accumulation of previous work, the researchers used single-cell sequencing technology to more systematically characterize the cellular and molecular spatial dynamic landscape of human hypothalamus development, and identified cell subsets and gene expression characteristics

▲The research system describes the cell lineage and gene regulation characteristics of human hypothalamus development (Image source: Reference [1])

In this study, the research team revealed the important regulators of differentiation to maintain the level of cell fate, and constructed gene regulatory networks during the differentiation of different neural stem cell subtypes into different terminal cells (including a variety of neurons and glial cells), indicating that Fate characterization of different cell types occurs early in development and is regulated by a combination of a diverse set of key transcription factors

▲Gene regulatory network of different neural stem cell subtypes (Image source: Reference [1])

Further studies by the researchers revealed the temporal signature of human hypothalamic neural stem cells in neurogenesis and gliogenesis, revealing the emergence of neuronal subtypes with distinct molecular signatures and spatial localizations that follow in spatial distribution from previous Anterior-posterior and outside-inside developmental patterns

In addition, the team identified the subtypes and molecular expression characteristics of different types of oligodendrocytes in the human hypothalamus, characterized the differentiation of oligodendrocyte lineages with two developmental trajectories, early and late, and oligodendrocytes at different developmental stages.

▲ Timing characteristics of hypothalamic neuron and glial cell subtype development (Image source: Reference [1])

Finally, through cross-species comparative analysis, the researchers found that human hypothalamic gliogenesis occurs in the early stages of gestation and displays a unique transcriptional profile expression signature compared to mice

This study provides a cellular map and gene expression signature of human hypothalamic development during early and mid-embryonic development, laying an important foundation for an in-depth understanding of its spatial and functional complexity, and the disease mechanisms caused by dysplasia

Note: The original text has been deleted

References:

[1] Xin Zhou et al.