Hormone Cell Atlas Helps Explain Cardiac Effects of GLP-1 Drugs

Utilizing data from the Human Cell Atlas, researchers have constructed a comprehensive map of cells that produce hormones and receive hormonal signals. The resulting Hormone Cell Atlas provides a resource for exploring hormone action and could help identify targets for hormone-based therapies.

In a study published in the journal Science, the atlas has already been used to uncover new insights into hormone signaling. The atlas revealed that hormone signaling extends far beyond endocrine glands (such as the thyroid, adrenal, and pituitary glands) and identified unexpected roles for immune cells.

“There are many more unexpected findings in the Hormone Cell Atlas, and exploring them will require effort from the whole community,” Professor Sarah Teichmann, chair in stem cell medicine at the University of Cambridge, told Technology Networks. “We hope this resource can help push forward our basic understanding of endocrine biology and provide new guidance for understanding and treating a wider range of diseases.”

Mapping the production and action of hormones

Hormones are chemical messengers transported in the bloodstream to specific targets, where they engage receptors to orchestrate essential processes such as metabolism, growth, and reproduction. Disorders that impact hormone production or action, for example, type 1 and type 2 diabetes, affect millions of people globally and often lack a cure.

“In the past, people mostly focused on classical endocrine glands. Now we know hormone production and hormone response are not limited to these organs. Fat, gut, immune cells, and vascular cells may also play important roles in hormonal signaling,” Teichmann said.

Integrating single-cell RNA sequencing datasets from over 100 published studies of 47 healthy adult tissues, the researchers assembled an atlas of over 14 million cells and nuclei across the human body. Using an analysis pipeline named hormone2cell and a custom-built database of over 150 hormones and their receptors, they predicted sites of hormone production and reception throughout the body.

“Public single-cell datasets often come from different studies, platforms, and tissues, so they are not easy to compare directly. But now we have better methods to integrate these datasets, annotate cell types, and look at possible hormone–receptor interactions,” explained Teichmann.

These advances made it possible to capture cells that both produce and respond to hormones and map long-range hormone axes and feedback loops across tissues, lineages, and cell types.

One of the most surprising findings from the study was an unexpected role for immune cells in hormone function. The researchers found that the gene encoding the gut hormone secretin, which is linked to digestive functions, is expressed in plasmacytoid dendritic cells (pDCs) across multiple tissues.

“We found that the secretin gene was upregulated following viral infection, including COVID-19, and then showed the same phenomenon in pDCs cultured and stimulated in vitro. However, whether pDCs secrete biologically active secretin in vivo, and what role this may play in antiviral immunity, will require further study,” Teichmann said.

Implications for hormone-based obesity treatments

Beyond improving understanding of hormone function, the Hormone Cell Atlas could also help identify potential target tissues and unexpected sites of action of hormone-based drugs.

Researchers used the atlas to investigate hormone receptors expressed across different cell types. This revealed co-expression of glucagon-like peptide-1 receptor and gastric inhibitory polypeptide receptor in cardiomyocytes and pacemaker cells of the heart. This provides a potential explanation for the cardiac effects of popular weight-loss drugs such as Ozempic™ (semaglutide), which act via these receptors.

“The atlas can support future drug development and safety studies by helping researchers predict possible tissue-specific effects, prioritize follow-up functional experiments, and design clinical studies that monitor the most relevant safety signals,” — Professor Sarah Teichmann.

Using the Hormone Cell Atlas, the researchers also profiled the hormone functions of adipocytes (fat cells), integrating nine human adipocyte datasets to generate an Adipocyte Cell Atlas. This provided insights into the different stages of fat development and revealed differences in endocrine functions across fat tissue depots and in people with obesity. “We think our data will help us understand how fat normally responds to hormones, and how this goes wrong in obesity,” Teichmann said.

Future applications of the Hormone Cell Atlas

The first version of the Hormone Cell Atlas is designed to be extensible, with Teichmann and colleagues planning to continue improving the atlas’ accuracy.

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This year marks the 10^th anniversary of the Human Cell Atlas, and more integrated single-cell atlases are in development. This additional data could help researchers perform more refined cell-type-level mapping of hormone production and hormone response. “As single-cell datasets and hormone–receptor annotations continue to grow, the Hormone Cell Atlas can also keep evolving and stay up to date,” explained Teichmann.

One future application of the Hormone Cell Atlas is in rare disease research. Using the atlas, Teichmann and colleagues were able to predict sites of gene expression whose disruption causes rare monogenic endocrine or metabolic disorders, including in tissues not currently linked to those disorders. “Many of these disorders are poorly understood and have limited treatment options. This resource therefore provides an invaluable opportunity to advance understanding of rare disease,” Teichmann said.

As an open resource, the researchers hope the Hormone Cell Atlas will inspire new studies into human endocrine disease and inform the rational drug discovery of hormone-based therapies.

Reference: Fei L, Huang-Doran I, Lawler K, et al. A Hormone Cell Atlas maps the human endocrine system at cellular resolution. Science. 2026. doi: 10.1126/science.aeb2672

About the interviewee:

Credit: Wellcome Sanger Institute.

Professor Sarah Teichmann completed her PhD at the MRC Laboratory of Molecular Biology in Cambridge, UK, and was a Beit Memorial Fellow at University College London. She established her research group at the MRC Laboratory of Molecular Biology in 2001, where her main discoveries included the finding that protein assembly pathways are stereotypical and conserved. In 2013, she transitioned to the Wellcome Genome Campus, where she became the first and, to date, the only faculty member appointed across both the EMBL-European Bioinformatics Institute and the Wellcome Sanger Institute. In 2016, she was appointed as the head of the cellular genetics program at the Wellcome Sanger Institute and co-founded the Human Cell Atlas initiative. From April 2024, she was appointed chair in stem cell medicine at the University of Cambridge, within the Department of Medicine and the Cambridge Stem Cell Institute. Additionally, Teichmann dedicates part of her time to GlaxoSmithKline, is a non-executive director of 10x Genomics, and has co-founded two startup companies. The Teichmann lab focuses on developing and applying cell atlas technologies to understand human tissue architecture, particularly examining how cellular diversity is generated in the immune system and during development.