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

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Abstract/Contents

Abstract
Hormones mediate long-range 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 84 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 molecular cell type identities, despite their comprising less than 1% of the transcriptome. Cells of similar cell types further display stage, subtype or organ-dependent specification of hormonal signaling, reflecting the precise control of global hormonal regulation. By linking ligand-expressing cells to the cells expressing the corresponding receptor, we constructed an organism-wide map of the hormonal cell communication network. This network was remarkably densely and robustly connected and included a myriad of feedback circuits. Although it includes classical hierarchical circuits (e.g. pituitary → peripheral endocrine gland → diverse cell types), the hormonal network is overall highly distributed without obvious network hubs or axes. Cross-species comparisons among humans, lemurs, and mice suggest that the mouse lemur better models human hormonal signaling, than does the mouse. Hormonal genes show a higher evolutionary conservation between human and lemur vs. human and mouse at both the genomic level (orthology-mapping and sequence identity) and the transcriptional level (cell type expression patterns). 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.

Description

Type of resource software, multimedia, text, Dataset
Date created October 10, 2023
Date modified October 12, 2023
Publication date August 29, 2022

Creators/Contributors

Author Liu, Shixuan
Author Ezran, Camille
Author Wang, Michael F. Z.
Author Li, Zhengda
Author Awayan, Kyle
Author Long, Jonathon Z.
Author De Vlaminck, Iwijn
Author Wang, Sheng
Author Kuo, Christin
Author Epelbaum, Jacques
Author Terrien, Jeremy
Author Krasnow, Mark A.
Author Ferrell, James E.

Subjects

Subject Hormone signaling
Subject Endocrinology
Subject Mouse lemurs
Subject Single cell RNA sequencing
Subject Network
Genre Software/code
Genre Code
Genre Documentation
Genre Data
Genre Computer program
Genre Data sets
Genre Dataset

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DOI https://doi.org/10.25740/yp860tc1411
Location https://purl.stanford.edu/yp860tc1411

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User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
License
This work is licensed under an MIT License.

Preferred citation

Preferred citation
Liu, S., Ezran, C., Wang, M., Li, Z., Awayan, K., Long, J., De Vlaminck, I., Wang, S., Kuo, C., Epelbaum, J., Terrien, J., Krasnow, M., and Ferrell, J. (2023). An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome . Stanford Digital Repository. Available at https://purl.stanford.edu/yp860tc1411. https://doi.org/10.25740/yp860tc1411.

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