肾上腺皮质
同源盒
内分泌学
醛固酮
内科学
生物
肾上腺
肾上腺疾病
转录因子
医学
葡萄糖稳态
基因
遗传学
胰岛素抵抗
胰岛素
作者
Ignacio del Valle,Matthew D. Young,Gerda Kildisiute,Olumide Ogunbiyi,Federica Buonocore,Ian C Simcock,Eleonora Khabirova,Berta Crespo,Nadjeda Moreno,Tony Brooks,Paola Niola,Katherine Swarbrick,Jenifer P Suntharalingham,Sinead McGlacken-Byrne,Owen J. Arthurs,Sam Behjati,John C. Achermann
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2023-07-24
卷期号:8 (14)
被引量:1
标识
DOI:10.1172/jci.insight.168177
摘要
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.
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