Del Valle, Ignacio;
Young, Matthew D;
Kildisiute, Gerda;
Ogunbiyi, Olumide K;
Buonocore, Federica;
Simcock, Ian C;
Khabirova, Eleonora;
... Achermann, John C; + view all
(2023)
An integrated single-cell analysis of human adrenal cortex development.
JCI Insight
, 8
(14)
, Article e168177. 10.1172/jci.insight.168177.
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Abstract
The adrenal glands synthesize and release essential steroid hormones such as cortisol and aldosterone, but many aspects of human adrenal gland development are not well understood. Here, we combined single-cell and bulk RNA sequencing, spatial transcriptomics, IHC, and micro-focus computed tomography to investigate key aspects of adrenal development in the first 20 weeks of gestation. We demonstrate rapid adrenal growth and vascularization, with more cell division in the outer definitive zone (DZ). Steroidogenic pathways favored androgen synthesis in the central fetal zone, but DZ capacity to synthesize cortisol and aldosterone developed with time. Core transcriptional regulators were identified, with localized expression of HOPX (also known as Hop homeobox/homeobox-only protein) in the DZ. Potential ligand-receptor interactions between mesenchyme and adrenal cortex were seen (e.g., RSPO3/LGR4). Growth-promoting imprinted genes were enriched in the developing cortex (e.g., IGF2, PEG3). These findings reveal aspects of human adrenal development and have clinical implications for understanding primary adrenal insufficiency and related postnatal adrenal disorders, such as adrenal tumor development, steroid disorders, and neonatal stress.
| Type: | Article |
|---|---|
| Title: | An integrated single-cell analysis of human adrenal cortex development |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/jci.insight.168177 |
| Publisher version: | https://doi.org/10.1172/jci.insight.168177 |
| Language: | English |
| Additional information: | © 2023, del Valle et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10173674 |
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