ESPEYB25 14. The Year in Science and Medicine Other Topics (4 abstracts)
14.19. A comprehensive spatio-cellular map of the human hypothalamus
Tadross JA , Steuernagel L , Dowsett GKC , Kentistou KA , Lundh S , Porniece M , Klemm P , Rainbow K , Hvid H , Kania K , Polex-Wolf J , Knudsen LB , Pyke C , Perry JRB , Lam BYH , Brüning JC & Yeo GSH
Nature. 2025 Mar;639(8055):708-716. doi: 10.1038/s41586-024-08504-8
Brief Summary: This human cell and molecular atlas study used data from post-mortem tissue from 8 brain donors of normal body mass index (BMI). It combined single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics on 433,369 human hypothalamic cells to create a comprehensive transcriptional map of the hypothalamus ("HYPOMAP"). The study is comparative (human vs. mouse), cross-sectional, and includes genomic association analysis with BMI.
While most prior knowledge in hypothalamic research stems from mouse models, HYPOMAP bridges this gap by offering detailed molecular and spatial characterization of human hypothalamic cell types, including previously overlooked non-neuronal populations such as astrocytes, oligodendrocytes, and ependymal cells. By precisely localizing key hypothalamic neurons and non-neuronal cell types involved in appetite regulation and metabolic control, this work bridges molecular endocrinology and neuroanatomy. Notably, the identification of distinct incretin receptor-expressing neuronal populations and the refined mapping of leptin–melanocortin circuits illuminate potential pathways through which steroid hormones might influence energy homeostasis and body weight regulation. This integration of cellular resolution data with systemic hormone profiles promises to enhance understanding of the hypothalamic role for sex- and age-related differences in metabolism and offers a robust platform for developing targeted interventions in metabolic disorders.
While the study is limited by a modest number of donors and an underrepresentation of sex, younger ages and disease diversity, the presented dataset provides a robust baseline for future research into hypothalamic dysfunction in obesity, metabolic disorders and beyond. To encourage further studies, the dataset is openly available.
Volume 22
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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