ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2020) 17 1.7 | DOI: 10.1530/ey.17.1.7

ESPEYB17 1. Pituitary and Neuroendocrinology Hypopituitarism: Disease Modeling and New Discoveries (3 abstracts)

1.7. Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators

Huisman C , Cho H , Brock O , Lim SJ , Youn SM , Park Y , Kim S , Lee SK , Delogu A & Lee JW



To read the full abstract: Nat Commun. 2019 Aug 16;10(1):3696. doi: 10.1038/s41467-019-11667-y. PMID: 31420539.

The hypothalamic arcuate nucleus (ARC) controls crucial physiological processes, such as growth, reproduction and energy homeostasis. However, it is unknown how ARC neurons gain their unique cellular identities and what are their developmental relationships. Here, the authors investigated ARC development by analyzing mouse embryonic ARCs with single cell RNA sequencing. When compared with a previous dataset on adult ARC neuronal types, they found that one cluster of embryonic ARC cells represented a pool of multiple types of developing ARC neurons. On closer analysis, the authors provided new markers required for systematically defining the developmental trajectories of ARC neurons, as well as key transcriptional regulators for fate determination and differentiation of ARC neurons. Furthermore, to validate two newly identified transcription factors implicated in specific cell types in the developing ARC, the authors knocked them out in mice; deletion of Foxp2 (enriched in developing Ghrh neurons) and Sox14 (enriched in developing kisspeptin neurons) led to reduced number of Ghrh neurons and complete infertility, respectively. Overall, this report greatly advances our understanding on how ARC neurons develop during embryogenesis and offers important clues to human diseases.