Authors
Maria E Kastriti, Denis Maksimov, Julia Krupinova, Marina Utkina, Dmitry Beltsevich, Anna Roslyakova, Olga Glazova, Samira Kaziakhmedova, Alina Ryabova, Anna Kuznetsova, Anastasia Shcherbakova, Ekaterina Bondarenko, Zoia Antysheva, Eugene Albert, Lilia Urusova, Anastasia Lapshina, Anastassia Chevais, Ekaterina Avsievich, Valentin Trofimov, Galina Melnichenko, Natalya Mokrysheva, Ivan Dedov, Lukas Englmaier, Julian Petersen, Oleg Gusev, Andreas Heinzel, Rainer Oberbauer, Pavel Volchkov, Peter V Kharchenko, Igor Adameyko
Published in
Nature genetics. Volume 58. Issue 9. Pages 2270-2283. Epub Sep 08, 2026.
Abstract
The adult adrenal cortex undergoes constant renewal, yet underlying human-specific mechanisms remain poorly understood. Here we generated single-cell and spatial transcriptomic atlases of adult human and mouse adrenal glands, leveraging single-cell-resolution spatial data and a rare clonal mosaic case for lineage inference. In humans, we identified age-associated zona glomerulosa (ZG) cell states with direct cortisol synthesis capacity and sex-specific differences in inferred cholesterol balance. Cross-species comparison revealed conserved aldosterone-producing ZG but notable divergence in zona fasciculata markers, absence of zona reticularis homologs in mice and differential SHH-WNT4 signaling in proliferating cells. We uncovered human WT1- capsule-to-ZG transition and vascular smooth muscle cell-to-steroidogenic transitions supported by mosaic lineage evidence. We revealed dispersed proliferating cortical SF1+EZH2+ cells throughout the human cortex in contrast with ZG restriction in mice. Taken together, our data expand the centripetal renewal model and establish a comparative framework for human adrenocortical biology.
PMID:
42711427
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.
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