Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus

Xin Zhou, Suijuan Zhong, Honghai Peng, Jing Liu, Wenyu Ding, Le Sun, Qiang Ma, Zeyuan Liu, Ruiguo Chen, Qian Wu and Xiaoqun Wang ()
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Xin Zhou: Chinese Academy of Sciences
Suijuan Zhong: Beijing Normal University
Honghai Peng: Jinan Central Hospital Affiliated to Shandong University
Jing Liu: Chinese Academy of Sciences
Wenyu Ding: Beijing Normal University
Le Sun: Chinese Academy of Sciences
Qiang Ma: Chinese Academy of Sciences
Zeyuan Liu: Chinese Academy of Sciences
Ruiguo Chen: Chinese Academy of Sciences
Qian Wu: Beijing Normal University
Xiaoqun Wang: Chinese Academy of Sciences

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract The neuroendocrine hypothalamus is the central regulator of vital physiological homeostasis and behavior. However, the cellular and molecular properties of hypothalamic neural progenitors remain unexplored. Here, hypothalamic radial glial (hRG) and hypothalamic mantle zone radial glial (hmRG) cells are found to be neural progenitors in the developing mammalian hypothalamus. The hmRG cells originate from hRG cells and produce neurons. During the early development of hypothalamus, neurogenesis occurs in radial columns and is initiated from hRG cells. The radial glial fibers are oriented toward the locations of hypothalamic subregions which act as a scaffold for neuronal migration. Furthermore, we use single-cell RNA sequencing to reveal progenitor subtypes in human developing hypothalamus and characterize specific progenitor genes, such as TTYH1, HMGA2, and FAM107A. We also demonstrate that HMGA2 is involved in E2F1 pathway, regulating the proliferation of progenitor cells by targeting on the downstream MYBL2. Different neuronal subtypes start to differentiate and express specific genes of hypothalamic nucleus at gestational week 10. Finally, we reveal the developmental conservation of nuclear structures and marker genes in mouse and human hypothalamus. Our identification of cellular and molecular properties of neural progenitors provides a basic understanding of neurogenesis and regional formation of the non-laminated hypothalamus.

Date: 2020
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DOI: 10.1038/s41467-020-17890-2

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