DLK1/PREF1 marks a novel cell population in the human adrenal cortex.
Adrenal cortex
Adrenocortical carcinoma
DLK1
Remodeling
Steroidogenesis
Journal
The Journal of steroid biochemistry and molecular biology
ISSN: 1879-1220
Titre abrégé: J Steroid Biochem Mol Biol
Pays: England
ID NLM: 9015483
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
26
09
2018
revised:
10
05
2019
accepted:
28
06
2019
pubmed:
3
7
2019
medline:
16
1
2020
entrez:
3
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31265901
pii: S0960-0760(18)30596-X
doi: 10.1016/j.jsbmb.2019.105422
pmc: PMC6736711
mid: NIHMS1041642
pii:
doi:
Substances chimiques
Calcium-Binding Proteins
0
DLK1 protein, human
0
Membrane Proteins
0
Aldosterone
4964P6T9RB
Cytochrome P-450 Enzyme System
9035-51-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105422Subventions
Organisme : BLRD VA
ID : I01 BX004665
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL027255
Pays : United States
Organisme : Medical Research Council
ID : MR/S022155/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : K08 CA222620
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM115428
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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