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Characterization of Aldosterone-producing Cell Cluster (APCC) at Single-cell Resolution
Norifusa Iwahashi1, Hironobu Umakoshi1, Tsugio Seki2
1Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
The Journal of Clinical Endocrinology and Metabolism
|July 7, 2022
Summary
Aldosterone-producing cell clusters (APCCs) in the adrenal cortex originate from zona glomerulosa (ZG) cells, as revealed by single-cell RNA sequencing. This finding helps understand the development of APCCs and primary aldosteronism.
Area of Science:
- Endocrinology
- Molecular Biology
- Genomics
Background:
- Aldosterone-producing cell clusters (APCCs) expressing aldosterone synthase (CYP11B2) are found in adult adrenal glands.
- These APCCs harbor somatic mutations also seen in aldosterone-producing adenomas (APAs), the main cause of primary aldosteronism.
- The developmental origins and gene expression of APCCs remain poorly understood.
Purpose of the Study:
- To analyze the transcriptome of APCCs at single-cell resolution.
- To infer the developmental trajectory of APCCs within the adrenal cortex.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was performed on cells from two adult adrenal glands.
- Unsupervised clustering and marker gene expression analysis identified 1765 adrenocortical cells.
- Subclustering and RNA velocity analysis were used to determine cell types and developmental direction.
Main Results:
- scRNA-seq identified distinct APCC and zona glomerulosa (ZG) cell clusters, with some cells showing transitional characteristics between ZG and fasciculata (ZF).
- RNA velocity analysis suggested a developmental trajectory from ZG cells towards APCCs.
- Many CYP11B2-positive cells also expressed CYP11B1 and/or CYP17A1, genes typically associated with cortisol production.
Conclusions:
- This study reveals the gene expression profiles of APCCs at the single-cell level.
- Evidence suggests that some ZG cells can remodel into APCCs, providing insight into their development.
- These findings contribute to understanding the pathogenesis of primary aldosteronism.
