dc.contributor.author
Altieri, Barbara
dc.contributor.author
Secener, A. Kerim
dc.contributor.author
Sai, Somesh
dc.contributor.author
Fischer, Cornelius
dc.contributor.author
Sbiera, Silviu
dc.contributor.author
Arampatzi, Panagiota
dc.contributor.author
Kircher, Stefan
dc.contributor.author
Herterich, Sabine
dc.contributor.author
Landwehr, Laura-Sophie
dc.contributor.author
Vitcetz, Sarah N.
dc.date.accessioned
2024-09-11T08:31:48Z
dc.date.available
2024-09-11T08:31:48Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/44899
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-44609
dc.description.abstract
The human adrenal gland is a complex endocrine tissue. Studies on adrenal renewal have been limited to animal models or human foetuses. Enhancing our understanding of adult human adrenal homeostasis is crucial for gaining insights into the pathogenesis of adrenal diseases, such as adrenocortical tumours.
Here, we present a comprehensive cellular genomics analysis of the adult human normal adrenal gland, combining single-nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland homeostasis. As expected, we identified primary cells of the various zones of the adrenal cortex and medulla, but we also uncovered additional cell types. They constitute the adrenal microenvironment, including immune cells, mostly composed of a large population of M2 macrophages, and new cell populations, including different subpopulations of vascular-endothelial cells and cortical-neuroendocrine cells. Utilizing spatial transcriptome and pseudotime trajectory analysis, we support evidence of the centripetal dynamics of adrenocortical cell maintenance and the essential role played by Wnt/β-catenin, sonic hedgehog, and fibroblast growth factor pathways in the adult adrenocortical homeostasis. Furthermore, we compared single-nuclei transcriptional profiles obtained from six healthy adrenal glands and twelve adrenocortical adenomas. This analysis unveiled a notable heterogeneity in cell populations within the adenoma samples. In addition, we identified six distinct adenoma-specific clusters, each with varying distributions based on steroid profiles and tumour mutational status.
Overall, our results provide novel insights into adrenal homeostasis and molecular mechanisms potentially underlying early adrenocortical tumorigenesis and/or autonomous steroid secretion. Our cell atlas represents a powerful resource to investigate other adrenal-related pathologies.
en
dc.format.extent
25 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
adrenal homeostasis
en
dc.subject
adrenocortical tumour
en
dc.subject
cortisol secretion
en
dc.subject
heterogeneity
en
dc.subject
microenvironment
en
dc.subject
spatial transcriptome
en
dc.subject
tumorigenesis
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften
dc.title
Single-nucleus and spatial transcriptome reveal adrenal homeostasis in normal and tumoural adrenal glands
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
e1798
dcterms.bibliographicCitation.doi
10.1002/ctm2.1798
dcterms.bibliographicCitation.journaltitle
Clinical and Translational Medicine
dcterms.bibliographicCitation.number
8
dcterms.bibliographicCitation.volume
14
dcterms.bibliographicCitation.url
https://doi.org/10.1002/ctm2.1798
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Chemie und Biochemie
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refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
2001-1326
refubium.resourceType.provider
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