Background

Hormones, which maintain homeostasis and regulate growth in our body, are chemical messengers that circulate throughout the body via the bloodstream. Until now, the medical community has focused on the one-to-one relationship between specific hormones secreted by individual endocrine organs, such as the pituitary gland, thyroid gland, pancreas, and adrenal glands, and their target organs. For example, insulin, secreted from the pancreas, binds to receptors on liver or muscle cells, thereby lowering blood glucose levels.

However, hormone signaling in our body actually operates as a much more complex network. This is because numerous hormones and receptors are distributed on the surface of cells throughout the body, interacting in complex ways. Conventional bulk analysis techniques have the limitation of analyzing a mixture of cells by crushing the entire tissue at once. As a result, it has been difficult to clearly distinguish which cells are receiving and responding to specific hormone signals. The lack of a precise map of the invisible hormone communication network has also hindered research aimed at elucidating the pathogenesis of complex metabolic diseases such as diabetes and obesity.

Key Findings

An international research team has created a cellular atlas of systemic endocrine signaling by integrating single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) technologies. The results of this study have been published in the international academic journal Nature Genetics, attracting attention from the scientific community. The researchers integrated and analyzed data from hundreds of thousands of single cells obtained from major endocrine organs and target tissues in the human body. They analyzed gene expression patterns and mapped the relationship between hormone ligands and receptors expressed by cells using a computer model.

In particular, the researchers made notable use of the CellChat system, a cell-to-cell communication analysis tool. This algorithm calculates the probability of communication between hormone-secreting and receiving cells based on gene expression levels at the single-cell level. In the process of analysis, the researchers examined the microenvironment within the pancreas at the cellular level, revealing previously unrecognized interactions. They discovered that a specific peptide secreted by pancreatic alpha cells not only regulates blood glucose levels but also binds to receptors on nearby immune cells, directly regulating local inflammatory responses. This clearly demonstrates the local endocrine signaling within the microenvironment that was not revealed by conventional analysis methods.

Significance and Prospects

The newly completed endocrine cell atlas is expected to serve as a new compass for understanding the pathogenesis of systemic diseases caused by hormone secretion abnormalities or metabolic disorders. It provides valuable basic data for the development of therapeutic agents for diseases in which multiple organs are simultaneously damaged, such as complex metabolic syndromes and multiple endocrine neoplasia. By visualizing the systemic hormone communication network, it is now possible to track the cascading effects of excessive hormone secretion on other organs throughout the body.

However, there are also clear technical limitations to this atlas. The transcriptome data used in the analysis is essentially a snapshot of the cellular state at a specific point in time. It does not reflect the dynamic factors in the body, such as blood flow rate, heart rate, and the periodic changes in hormone levels throughout the day and night. Since the activity of hormones varies greatly depending on their secretion cycle, further research is needed to address these limitations. Ultimately, the combination with precise biological models that simulate the dynamic environment in vivo is a challenge to be addressed in the future.