SFEBES2025 Oral Communications Metabolism, Obesity and Diabetes (6 abstracts)
Development of the hormone cell atlas
Isabel Huang-Doran 1 , Lijiang Fei 2 , Ken To 3 , Jaume Margalef-Rieres 1 , Jan Patrick Pett 3 , Kevin Mendez Acevedo 1 , Dinesh Shah 1 , Tessa Cacciottolo 1 , Chuan Xu 2 , Duy Pham 2 , Alexander Predeus 3 , Ling Yang 3 , Sarah Teichmann 2,3,4 & I Sadaf Farooqi 1
1Institute of Metabolic Science-Metabolic Research Laboratories, Cambridge, United Kingdom; 2Cambridge Stem Cell Institute, Cambridge, United Kingdom; 3Wellcome Sanger Institute, Cambridge, United Kingdom; 4Department of Medicine, University of Cambridge, Cambridge, United Kingdom
Hormones are secreted by diverse cell types across endocrine and non-endocrine tissues, acting via cognate receptors to coordinate cellular responses. A systematic understanding of hormone production and action across human tissues, at cell type resolution, is lacking. We have developed the Hormone Cell Atlas, a unique single cell transcriptomic resource integrating 46 tissues from over 1000 donors, from which we map the expression of over 500 genes encoding hormones and their receptors. We profile cross-tissue, sex-specific expression of genes involved in peptide, steroid and amine-derived hormone production, defining classical endocrine and non-professional hormone-producing cell types. We survey the expression and specificity of G protein coupled receptors, nuclear hormone receptors and enzyme-linked receptors in central and peripheral tissues, including those representing major drug targets, and uncover previously uncharacterised sites of hormone action. We next leverage the Hormone Cell Atlas to assemble cell type specific intracellular hormone regulatory networks. Focusing on adipose tissue, we identify regulatory networks in adipocytes centred on the glucocorticoid receptor (NR3C1) and thyroid hormone receptor beta (THRB), and validate downstream targets in primary human adipocytes cultured in vitro. Investigating depot and BMI-dependent patterns of hormone production and receptivity, we highlight the androgen receptor (AR) as a prominent and BMI-associated transcript in subcutaneous adipocytes, explore associated transcriptional signatures, and offer new insights into hormonal regulation of adipose tissue function. Finally, using our directory of hormone-receptor interactions, we assemble a system-wide, hormone-mediated cellular interaction network, including feedback and crosstalk within and across classical endocrine axes. The Hormone Cell Atlas, accessible via a searchable web-based portal, will provide a valuable resource for understanding hormone regulation and action in health and disease.
Volume 109
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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