An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome

Abstract

AbstractHormones coordinate long-range cell-cell communication in multicellular organisms and play vital roles in normal physiology, metabolism, and health. Using the newly-completed organism-wide single cell transcriptional atlas of a non-human primate, the mouse lemur (Microcebus murinus), we have systematically identified hormone-producing and -target cells for 87 classes of hormones, and have created a browsable atlas for hormone signaling that reveals previously unreported sites of hormone regulation and species-specific rewiring. Hormone ligands and receptors exhibited cell-type-dependent, stereotypical expression patterns, and their transcriptional profiles faithfully classified the discrete cell types defined by the full transcriptome, despite their comprising less than 1% of the transcriptome. Although individual cell types generally exhibited the same characteristic patterns of hormonal gene expression, a number of examples of similar or seemingly-identical cell types (e.g., endothelial cells of the lung versus of other organs) displayed different hormonal gene expression patterns. By linking ligand-expressing cells to the cells expressing the corresponding receptor, we constructed an organism-wide map of the hormonal cell-cell communication network. The hormonal cell-cell network was remarkably densely and robustly connected, and included classical hierarchical circuits (e.g. pituitary → peripheral endocrine gland → diverse cell types) as well as examples of highly distributed control. The network also included both well-known examples of feedback loops and a long list of potential novel feedback circuits. This primate hormone atlas provides a powerful resource to facilitate discovery of regulation on an organism-wide scale and at single-cell resolution, complementing the single-site-focused strategy of classical endocrine studies. The network nature of hormone regulation and the principles discovered here further emphasize the importance of a systems approach to understanding hormone regulation.