A Hormone Cell Atlas maps the human endocrine system at cellular resolution.
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| Title: | A Hormone Cell Atlas maps the human endocrine system at cellular resolution. |
|---|---|
| Authors: | Fei, Lijiang (AUTHOR), Huang-Doran, Isabel (AUTHOR), Lawler, Katherine (AUTHOR), Yu, Yizhou (AUTHOR), Pett, Jan Patrick (AUTHOR), Méndez-Acevedo, Kevin M. (AUTHOR), Shah, Dinesh (AUTHOR), Margalef-Rieres, Jaume (AUTHOR), Pohlman, Joseph S. (AUTHOR), Cakir, Batuhan (AUTHOR), Moy, Madelyn R. (AUTHOR), Legg, Robert G. (AUTHOR), Xu, Chuan (AUTHOR), To, Ken (AUTHOR), Pham, Duy (AUTHOR), Predeus, Alexander V. (AUTHOR), Hanssen, Ruth (AUTHOR), Cacciottolo, Tessa M. (AUTHOR), Kapuge, Rakesh K. (AUTHOR), Polanski, Krzysztof (AUTHOR) |
| Source: | Science. 7/2/2026, Vol. 393 Issue 6806, p1-18. 18p. |
| Subjects: | Endocrine system, Hormone receptors, Tissue analysis, Endocrine diseases, Adipogenesis, Transcriptomes, Hormone regulation |
| Abstract: | Hormones act across tissues and organs to coordinate physiological functions. Drawing inspiration from the Human Cell Atlas, we analyzed the expression of 379 hormone and receptor genes in a transcriptomic dataset comprising 14 million single cells and nuclei across 47 human tissues. Using hormone2cell, we mapped putative hormone-producing and hormone-receiving cell types, defining tissue-specific and cross-tissue endocrine signatures. We predicted nonclassical sites of hormone expression, including secretin in plasmacytoid dendritic cells, inferred convergent hormone action and endocrine feedback loops, and implicated cell populations in monogenic endocrine disorders. In a cross-tissue integration of adipocyte datasets, we uncovered dynamic endocrine programs across depots, within adipocyte subtypes and through adipogenic differentiation. Cumulatively, the Hormone Cell Atlas (hormonecellatlas.org.uk) provides a comprehensive framework for dissecting hormonal impact on health and disease. Editor's summary: The traditional view of hormones is that they are chemical messengers produced by known endocrine glands and then secreted into the blood to reach their target organs. This definition has expanded to accommodate nonclassical hormones secreted by tissues other than specific glands, such as adipose tissue, and new hormones that meet this expanded definition continue to be discovered periodically. A large-scale effort by Fei et al. presents an atlas of known hormones acting throughout the human body, mapping out the cells that produce and respond to them across 47 tissue types at single-cell resolution. —Yevgeniya Nusinovich INTRODUCTION: Hormones are chemical messengers secreted into the blood, which act on distant targets to coordinate fundamental physiological processes, such as growth, reproduction, and metabolism. Human disorders of hormone production and/or action, such as type 1 and 2 diabetes, obesity, and thyroid disease, affect millions of people globally. In recent decades, an increasing number of hormones have been identified, highlighting the complexity and distributed nature of the endocrine system. RATIONALE: To date, most studies of hormone synthesis and action have focused on a particular hormone, receptor, or target organ. Here, we set out to systematically investigate the production and action of more than 162 hormones across multiple human tissues at cellular resolution by constructing a human Hormone Cell Atlas (hormonecellatlas.org.uk). RESULTS: We harmonized single-cell and single-nucleus transcriptomic data from 108 studies of 47 healthy adult tissues, generating a cross-tissue reference atlas spanning 10 biological systems. We also assembled a comprehensive database of 162 hormones and their cognate receptors. Using hormone2cell, an analytical framework that incorporates the enzymes required to synthesize hormones among other features, we predicted hormone-producing and hormone-responsive cell types on the basis of single-cell transcriptomic data, charting a cell type–resolved map of endocrine signaling across the human body. Globally, all 47 tissues contained predicted hormone-producing or hormone-responsive cell populations. Across tissues, hormone expression showed strong cell type specificity, particularly for classical endocrine hormones, such as insulin, whereas receptor expression was broadly distributed, suggesting extensive interorgan cross-talk mediated by endocrine signaling networks. Among our findings, hormone expression in immune cells was more widespread than previously appreciated. The hormone secretin was detected at the transcript level in circulating and tissue-resident plasmacytoid dendritic cells (pDCs) and, at the protein level, in human pDCs. Secretin transcripts were up-regulated after in vitro stimulation of blood pDCs, suggesting a role for this gut-derived hormone in human immune regulation. We uncovered classical hormone feedback loops within the Hormone Cell Atlas, predicting cross-talk between endocrine axes traditionally viewed as independent. We used the atlas to explore the effects of hormone-based therapies. For example, we found that GLP1R, encoding glucagon-like peptide–1 receptor, and GIPR, encoding gastric inhibitory polypeptide receptor (both targets of obesity medications), were coexpressed in cardiomyocytes and cardiac pacemaker cells, suggesting a potential mechanistic basis for the effects of these drugs, which requires further exploration. Given the critical role of adipose tissue dysfunction in the pathophysiology of obesity and its complications, we performed a cross-tissue integration of nine human adipocyte datasets. This revealed dynamic endocrine programs during adipocyte differentiation, across adipose tissue depots, and characteristic patterns in people with obesity. Finally, we mapped the expression of more than 400 genes whose disruption causes human monogenic endocrine and metabolic disorders, predicting sites of gene expression. CONCLUSION: As an open and extensible resource, the Hormone Cell Atlas provides a framework for dissecting human endocrine physiology, serves as a reference for mechanistic studies of endocrine disease, and informs a rational approach to the identification and validation of therapeutic targets. Construction and applications of the human Hormone Cell Atlas.: Single-cell and single-nucleus transcriptomic data from 47 human tissues were integrated to construct a cross-tissue reference atlas. This was combined with a curated database of human hormones and cognate receptors. Using a framework called hormone2cell, we predicted hormone production and action at cellular resolution, enabling cross-tissue endocrine analysis and interrogation of disease-associated gene expression. GPCRs, G protein–coupled receptors; NHRs, nuclear hormone receptors. [Figure created with BioRender.com] [ABSTRACT FROM AUTHOR] |
| Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 195069945 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: A Hormone Cell Atlas maps the human endocrine system at cellular resolution. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Fei%2C+Lijiang%22">Fei, Lijiang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Huang-Doran%2C+Isabel%22">Huang-Doran, Isabel</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lawler%2C+Katherine%22">Lawler, Katherine</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yu%2C+Yizhou%22">Yu, Yizhou</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pett%2C+Jan+Patrick%22">Pett, Jan Patrick</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Méndez-Acevedo%2C+Kevin+M%2E%22">Méndez-Acevedo, Kevin M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shah%2C+Dinesh%22">Shah, Dinesh</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Margalef-Rieres%2C+Jaume%22">Margalef-Rieres, Jaume</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pohlman%2C+Joseph+S%2E%22">Pohlman, Joseph S.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cakir%2C+Batuhan%22">Cakir, Batuhan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Moy%2C+Madelyn+R%2E%22">Moy, Madelyn R.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Legg%2C+Robert+G%2E%22">Legg, Robert G.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xu%2C+Chuan%22">Xu, Chuan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22To%2C+Ken%22">To, Ken</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pham%2C+Duy%22">Pham, Duy</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Predeus%2C+Alexander+V%2E%22">Predeus, Alexander V.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hanssen%2C+Ruth%22">Hanssen, Ruth</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cacciottolo%2C+Tessa+M%2E%22">Cacciottolo, Tessa M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kapuge%2C+Rakesh+K%2E%22">Kapuge, Rakesh K.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Polanski%2C+Krzysztof%22">Polanski, Krzysztof</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Science%22">Science</searchLink>. 7/2/2026, Vol. 393 Issue 6806, p1-18. 18p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Endocrine+system%22">Endocrine system</searchLink><br /><searchLink fieldCode="DE" term="%22Hormone+receptors%22">Hormone receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Tissue+analysis%22">Tissue analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Endocrine+diseases%22">Endocrine diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Adipogenesis%22">Adipogenesis</searchLink><br /><searchLink fieldCode="DE" term="%22Transcriptomes%22">Transcriptomes</searchLink><br /><searchLink fieldCode="DE" term="%22Hormone+regulation%22">Hormone regulation</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Hormones act across tissues and organs to coordinate physiological functions. Drawing inspiration from the Human Cell Atlas, we analyzed the expression of 379 hormone and receptor genes in a transcriptomic dataset comprising 14 million single cells and nuclei across 47 human tissues. Using hormone2cell, we mapped putative hormone-producing and hormone-receiving cell types, defining tissue-specific and cross-tissue endocrine signatures. We predicted nonclassical sites of hormone expression, including secretin in plasmacytoid dendritic cells, inferred convergent hormone action and endocrine feedback loops, and implicated cell populations in monogenic endocrine disorders. In a cross-tissue integration of adipocyte datasets, we uncovered dynamic endocrine programs across depots, within adipocyte subtypes and through adipogenic differentiation. Cumulatively, the Hormone Cell Atlas (hormonecellatlas.org.uk) provides a comprehensive framework for dissecting hormonal impact on health and disease. Editor's summary: The traditional view of hormones is that they are chemical messengers produced by known endocrine glands and then secreted into the blood to reach their target organs. This definition has expanded to accommodate nonclassical hormones secreted by tissues other than specific glands, such as adipose tissue, and new hormones that meet this expanded definition continue to be discovered periodically. A large-scale effort by Fei et al. presents an atlas of known hormones acting throughout the human body, mapping out the cells that produce and respond to them across 47 tissue types at single-cell resolution. —Yevgeniya Nusinovich INTRODUCTION: Hormones are chemical messengers secreted into the blood, which act on distant targets to coordinate fundamental physiological processes, such as growth, reproduction, and metabolism. Human disorders of hormone production and/or action, such as type 1 and 2 diabetes, obesity, and thyroid disease, affect millions of people globally. In recent decades, an increasing number of hormones have been identified, highlighting the complexity and distributed nature of the endocrine system. RATIONALE: To date, most studies of hormone synthesis and action have focused on a particular hormone, receptor, or target organ. Here, we set out to systematically investigate the production and action of more than 162 hormones across multiple human tissues at cellular resolution by constructing a human Hormone Cell Atlas (hormonecellatlas.org.uk). RESULTS: We harmonized single-cell and single-nucleus transcriptomic data from 108 studies of 47 healthy adult tissues, generating a cross-tissue reference atlas spanning 10 biological systems. We also assembled a comprehensive database of 162 hormones and their cognate receptors. Using hormone2cell, an analytical framework that incorporates the enzymes required to synthesize hormones among other features, we predicted hormone-producing and hormone-responsive cell types on the basis of single-cell transcriptomic data, charting a cell type–resolved map of endocrine signaling across the human body. Globally, all 47 tissues contained predicted hormone-producing or hormone-responsive cell populations. Across tissues, hormone expression showed strong cell type specificity, particularly for classical endocrine hormones, such as insulin, whereas receptor expression was broadly distributed, suggesting extensive interorgan cross-talk mediated by endocrine signaling networks. Among our findings, hormone expression in immune cells was more widespread than previously appreciated. The hormone secretin was detected at the transcript level in circulating and tissue-resident plasmacytoid dendritic cells (pDCs) and, at the protein level, in human pDCs. Secretin transcripts were up-regulated after in vitro stimulation of blood pDCs, suggesting a role for this gut-derived hormone in human immune regulation. We uncovered classical hormone feedback loops within the Hormone Cell Atlas, predicting cross-talk between endocrine axes traditionally viewed as independent. We used the atlas to explore the effects of hormone-based therapies. For example, we found that GLP1R, encoding glucagon-like peptide–1 receptor, and GIPR, encoding gastric inhibitory polypeptide receptor (both targets of obesity medications), were coexpressed in cardiomyocytes and cardiac pacemaker cells, suggesting a potential mechanistic basis for the effects of these drugs, which requires further exploration. Given the critical role of adipose tissue dysfunction in the pathophysiology of obesity and its complications, we performed a cross-tissue integration of nine human adipocyte datasets. This revealed dynamic endocrine programs during adipocyte differentiation, across adipose tissue depots, and characteristic patterns in people with obesity. Finally, we mapped the expression of more than 400 genes whose disruption causes human monogenic endocrine and metabolic disorders, predicting sites of gene expression. CONCLUSION: As an open and extensible resource, the Hormone Cell Atlas provides a framework for dissecting human endocrine physiology, serves as a reference for mechanistic studies of endocrine disease, and informs a rational approach to the identification and validation of therapeutic targets. Construction and applications of the human Hormone Cell Atlas.: Single-cell and single-nucleus transcriptomic data from 47 human tissues were integrated to construct a cross-tissue reference atlas. This was combined with a curated database of human hormones and cognate receptors. Using a framework called hormone2cell, we predicted hormone production and action at cellular resolution, enabling cross-tissue endocrine analysis and interrogation of disease-associated gene expression. GPCRs, G protein–coupled receptors; NHRs, nuclear hormone receptors. [Figure created with BioRender.com] [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1126/science.aeb2672 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 18 StartPage: 1 Subjects: – SubjectFull: Endocrine system Type: general – SubjectFull: Hormone receptors Type: general – SubjectFull: Tissue analysis Type: general – SubjectFull: Endocrine diseases Type: general – SubjectFull: Adipogenesis Type: general – SubjectFull: Transcriptomes Type: general – SubjectFull: Hormone regulation Type: general Titles: – TitleFull: A Hormone Cell Atlas maps the human endocrine system at cellular resolution. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Fei, Lijiang – PersonEntity: Name: NameFull: Huang-Doran, Isabel – PersonEntity: Name: NameFull: Lawler, Katherine – PersonEntity: Name: NameFull: Yu, Yizhou – PersonEntity: Name: NameFull: Pett, Jan Patrick – PersonEntity: Name: NameFull: Méndez-Acevedo, Kevin M. – PersonEntity: Name: NameFull: Shah, Dinesh – PersonEntity: Name: NameFull: Margalef-Rieres, Jaume – PersonEntity: Name: NameFull: Pohlman, Joseph S. – PersonEntity: Name: NameFull: Cakir, Batuhan – PersonEntity: Name: NameFull: Moy, Madelyn R. – PersonEntity: Name: NameFull: Legg, Robert G. – PersonEntity: Name: NameFull: Xu, Chuan – PersonEntity: Name: NameFull: To, Ken – PersonEntity: Name: NameFull: Pham, Duy – PersonEntity: Name: NameFull: Predeus, Alexander V. – PersonEntity: Name: NameFull: Hanssen, Ruth – PersonEntity: Name: NameFull: Cacciottolo, Tessa M. – PersonEntity: Name: NameFull: Kapuge, Rakesh K. – PersonEntity: Name: NameFull: Polanski, Krzysztof IsPartOfRelationships: – BibEntity: Dates: – D: 02 M: 07 Text: 7/2/2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 00368075 Numbering: – Type: volume Value: 393 – Type: issue Value: 6806 Titles: – TitleFull: Science Type: main |
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