An initiative to map hormones in the human body has revealed the breadth and complexity of the endocrine system and could deliver transformative insights into disease for the creation of new therapeutics.
The Hormone Cell Atlas provides a comprehensive framework to explore the impact of these chemical messengers in health and disease, combining a system-level overview with detail at a cellular level.
Its creation incorporates transcriptome-level data from dozens of tissue types and involves the expression of hundreds of hormone and receptor genes in millions of cells and nuclei.
The research, in Science, reveal the distributed and interconnected nature of hormonal regulation, involving a wide repertoire of cell types derived from multiple cell lineages.
These cells show the potential to both synthesize or modulate hormones, with most expressing receptor genes that may integrate signals from multiple hormones.
“These findings have implications not only for understanding physiology and its perturbation in disease, but also for understanding the pleiotropic effects of hormone-based therapies,” reported Lijiang Fei, PhD, from the University of Cambridge, and co-workers.
“For example, expression of GLP1R and GIPR in cardiomyocytes and cardiac pacemaker cells raises the possibility that any cardiovascular benefits or risks of these drugs may arise from direct receptor engagement, not solely from weight loss or improvements in glycemic control.”
Hormones are secreted by endocrine glands and act across tissues and organs to coordinate physiological functions, orchestrating metabolism, growth, reproduction, and other essential physiological processes using tightly regulated synthesis and release.
Inspired by the creation of the Human Cell Atlas, which aims to map all the cells in the human body, Fei and co-workers set out to improve understanding of the synthesis and action of hormones.
Using information from that initiative, the team analyzed the expression of 379 hormone and receptor genes in a transcriptomic dataset comprising 14 million single cells and nuclei across 47 human tissues.
The team mapped the cellular architecture of hormone production and action across diverse tissues and lineages, charted long-range endocrine feedback loops, and localized the expression of genes associated with monogenic endocrine and metabolic disease at cell type resolution across a variety of tissues.
Through this, they created a comprehensive, high-resolution, browsable map that predicted hormone production at cellular resolution.
“The atlas not only recovers classical endocrine axes but also illuminates underappreciated sites of hormone production and action,” the authors pointed out.
“We highlight important principles in endocrine biology, including local modulation of steroidogenic signals in peripheral tissues, specialized vascular-endocrine niches, and the role of adipocytes as dynamic hormone-producing and -sensing cell types.”
They conclude: “This accessible, adaptable resource establishes a dynamic framework for dissecting endocrine physiology and paves the way for mechanistic and physiological studies, which together may deliver transformative insights into human endocrine disease and inform rational drug discovery.”
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