SFEBES2022 Oral Poster Presentations Adrenal and Cardiovascular (4 abstracts)
Delta-like non-canonical notch ligand 1 (DLK1)-expressing adrenocortical progenitor cells: role in adrenal turnover, remodeling and tumorigenesis in mice
Katia Mariniello 1 , James Pittaway 1 , Irene Hadjidemetriou 1 , Kleiton Borges 2 , Milena Doroszko 3 , Mabrouka Doghman 4 , Enzo Lalli 4 , Nafis Rahman 3 , David Breault 2 , Emanuel Rognoni 1 & Leonardo Guasti 1
1Centre for Endocrinology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; 2Division of Endocrinology, Boston Children’s Hospital, Boston, MA 02115, United state of America; Department of Pediatrics, Harvard Medical School, Boston, United state of America; 3Institute of Biomedicine, Faculty of Medicine, University of Turku, Turku, Finland; 4Institut de Pharmacologie Moléculaire et Cellulaire CNRS, Valbonne, France; Associated International Laboratory (LIA) NEOGENEX CNRS, Valbonne, France; University of Nice-Sophia-Antipolis, Valbonne, France, Valbonne, France
The adrenal cortex is a dynamic organ that undergoes self-renewal. In the mouse it is divided into two concentric layers, the outer zona glomerulosa (ZG) and the inner zona fasciculata (ZF), that secrete aldosterone and corticosterone, respectively. Capsular and subcapsular stem/progenitor cells differentiate and migrate in a centripetal fashion to repopulate the gland until they reach the juxtamedullary region where they undergo senescence and apoptosis. Our lab has previously shown that Delta like non-canonical Notch ligand 1 (Dlk1) is expressed in partially undifferentiated cells of the subcapsular region in rat and human adrenals. Dlk1 is expressed in Steroidogenic Factor-1 (Sf1)-negative capsular cells throughout life, but, differently from Gli-1 capsular cells, its expression decreases significantly both postnatally and with aging. Genetic lineage tracing analyses using a tamoxifen inducible Dlk1CreERT2 mouse model carrying the R26tdTom reporter showed that capsular Dlk1 cells are indeed steroidogenic progenitors; these cells are particularly active during the embryonic life, whilst being near dormant postnatally, especially in males. However, in postnatal life, Dlk1 cells can be re-activated to regenerate the ZF after dexamethasone treatment, demonstrating their plasticity during adrenal remodelling treatment mimicking pharmacological interventions in humans. Finally, we present preliminary data on the potential role of Dlk1 cells in the pathogenesis of adrenocortical tumorigenesis and carcinogenesis using appropriate transgenic mouse models.
Volume 86
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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