biostudies-literatureUnknownMariniello KNIDDK NIH HHSBiotechnology and Biological Sciences Research CouncilDisruption of processes involved in tissue development and homeostatic self-renewal is increasingly implicated in cancer initiation, progression, and recurrence. The adrenal cortex is a dynamic tissue that undergoes life-long turnover. Here, using genetic fate mapping and murine adrenocortical carcinoma (ACC) models, we have identified a population of adrenocortical stem cells that express delta-like non-canonical Notch ligand 1 (DLK1). These cells are active during development, near dormant postnatally but are re-expressed in ACC. In a study of over 200 human ACC samples, we have shown DLK1 expression is ubiquitous and is an independent prognostic marker of recurrence-free survival. Paradoxically, despite its progenitor role, spatial transcriptomic analysis has identified DLK1 expressing bioRxiv : the preprint server for biology2024.08.22.609117https://www.ebi.ac.uk/biostudies/studies/S-EPMC11370565biostudies-literatureDlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.PMC11370565BB/V007246/1R01 DK123694Tamburello MPittaway JFHPalazzo FRonchi CLSigala SKroiss MAbdel-Aziz TEParvanta LLim JARuiz-Babot GDoroszko MFoster JRayner OBreault DTGuasti LAltieri BHadjidemetriou IGaston-Massuet CWierman MGomez-Sanchez CEDi Marco ADrake WMBorges KSChung TTRahman NRibeiro CAbate AKiseljak-Vassiliades KMariniello KHantel CSosabowski JFassnacht MSbiera SCleaver JTaylor DRRognoni EfalseDlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.Disruption of processes involved in tissue development and homeostatic self-renewal is increasingly implicated in cancer initiation, progression, and recurrence. The adrenal cortex is a dynamic tissue that undergoes life-long turnover. Here, using genetic fate mapping and murine adrenocortical carcinoma (ACC) models, we have identified a population of adrenocortical stem cells that express delta-like non-canonical Notch ligand 1 (DLK1). These cells are active during development, near dormant postnatally but are re-expressed in ACC. In a study of over 200 human ACC samples, we have shown DLK1 expression is ubiquitous and is an independent prognostic marker of recurrence-free survival. Paradoxically, despite its progenitor role, spatial transcriptomic analysis has identified DLK1 expressing 2024-01-01T00:00:00Z2024 Aug2025-04-22T20:51:24.296Z2025-04-06T03:20:40.962ZS-EPMC113705653922921710.1101/2024.08.22.609117