Cell atlas of the human hypothalamus published

A detailed map of the human brain region known as the hypothalamus has been created using advanced genetic techniques.

The hypothalamus controls fundamental biological functions such as appetite, body temperature, sleep, the stress response, and social behaviours. It has been linked to a range of medical conditions, including obesity and sleep and stress disorders. The map developed, known as a cell atlas, shows a huge variety of cells in the region and highlights key differences between the hypothalamus in mice and humans.

First author, Dr John Tadross, and senior-author, Professor Giles Yeo, from the University of Cambridge told Nature: 'This achievement marks a major milestone on our journey to understanding the neurocircuitry that regulates energy balance and its responses to conditions of energy imbalance, such as obesity and the weight-loss disease cachexia.'

Publishing their findings in Nature, researchers from the University of Cambridge and the Max Planck Institute for Metabolism Research in Germany, used two advanced genetic techniques to study over 400,000 brain cells from donated human tissue of the hypothalamus.

One method, known as single-nuclei RNA-sequencing, identified and characterised different cell types based on their genes. A second method, known as spatial transcriptomics, mapped the cells' locations within the brain.

Over 450 types of brain cells in the hypothalamus were identified during the study, including specific brain cells that release appetite-regulating proteins that could potentially be targeted therapeutically to help control appetite. Gene variants associated with body mass index (BMI), an estimate of body fat, were also identified, including of one gene, CORO1A, that had not been linked previously to BMI.

Furthermore, by comparing the human hypothalamus cell atlas with the mouse hypothalamus cell atlas they had previously published, the researchers identified key differences between the hypothalamus of humans and mice. Mice are commonly used as models for human research, as such, understanding these differences is crucial for translational studies.

While this research is an important step toward understanding how the hypothalamus controls body functions, the study included the brains of only 18 people, mostly men, thus future research on a more diverse group of samples will be needed.

'In terms of sheer scale, the authors have... far surpassed previous work to generate the most definitive molecular census of hypothalamic cellular diversity in healthy humans to date,' an anonymous expert who reviewed the study told Nature. 'This resource will be critical for future research on human hypothalamic cells, circuits, diseases and potential therapeutics.'

The human hypothalamus cell atlas has been made publicly available as a resource called HYPOMAP. The authors hope that this detailed brain map paves the way for a deeper understanding of conditions such as obesity, stress disorders, and sleep disturbances, enabling more targeted treatments based on human brain function.