ArticleThe Journal of steroid biochemistry and molecular biology2019
DLK1/PREF1 marks a novel cell population in the human adrenal cortex.
Article in The Journal of steroid biochemistry and molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Human and mouse adrenal glands are characterized by species-specific steroidogenic states and tissue turnover.Nature genetics · 2026Article
- DLK1: a novel therapeutic target in cancer.Endocrine-related cancer · 2026Review
- Identification of the Notch ligand DLK1 as an immunotherapeutic target and regulator of tumor cell plasticity and chemoresistance in adrenocortical carcinoma.Nature communications · 2025Article
- Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.Cancer communications (London, England) · 2025Article
- Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.bioRxiv : the preprint server for biology · 2024Article
- Single-nucleus and spatial transcriptome reveal adrenal homeostasis in normal and tumoural adrenal glands.Clinical and translational medicine · 2024Article
- Generation of glucocorticoid-producing cells derived from human pluripotent stem cells.Cell reports methods · 2023Article
- An integrated single-cell analysis of human adrenal cortex development.JCI insight · 2023Article
- The Immunotherapy Landscape in Adrenocortical Cancer.Cancers · 2021Review
- Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?Cancers · 2021Article
- Stem cell function and plasticity in the normal physiology of the adrenal cortex.Molecular and cellular endocrinology · 2021Review
- Stem Cells, Self-Renewal, and Lineage Commitment in the Endocrine System.Frontiers in endocrinology · 2019Review
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
The adrenal cortex governs fundamental metabolic processes though synthesis of glucocorticoid, mineralocorticoids and androgens. Studies in rodents have demonstrated that the cortex undergoes a self-renewal process and that capsular/subcapsular stem/progenitor cell pools differentiate towards functional steroidogenic cells supporting the dynamic centripetal streaming of adrenocortical cells throughout life. We previously demonstrated that the Notch atypical ligand Delta-like homologue 1 (DLK1)/preadipocyte factor 1 (PREF1) is expressed in subcapsular Sf1 and Shh-positive, CYP11B1-negative and CYP11B2-partially positive cortical progenitor cells in rat adrenals, and that secreted DLK1 can modulate GLI1 expression in H295R cells. Here we show that the human adrenal cortex remodels with age to generate clusters of relatively undifferentiated cells expressing DLK1. These clusters (named DLK1-expressing cell clusters or DCCs) increased with age in size and were found to be different entities to aldosterone-producing cell clusters, another well-characterized and age-dependent cluster structure. DLK1 was markedly overexpressed in adrenocortical carcinomas but not in aldosterone-producing adenomas. Thus, this data identifies a novel cell population in the human adrenal cortex and might suggest a yet-to be identified role of DLK1 in the pathogenesis of adrenocortical carcinoma in humans.
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