Characterization of Aldosterone-producing Cell Cluster (APCC) at Single-cell Resolution

Norifusa Iwahashi, Hironobu Umakoshi, Tsugio Seki, Celso E. Gomez-Sanchez, Kuniaki Mukai, Makoto Suematsu, Yuta Umezawa, Mototsugu Oya, Takeo Kosaka, Masahide Seki, Yutaka Suzuki, Yutaka Horiuchi, Yoshihiro Ogawa, Koshiro Nishimoto

研究成果: Article査読

抄録

Context: The adrenal cortex consists of zona glomerulosa (ZG), fasciculata (ZF), and reticularis. Aldosterone-producing cell clusters (APCCs) that strongly express aldosterone synthase (CYP11B2) are frequently found in adult adrenals and harbor somatic mutations that are also detected in aldosterone-producing adenomas (APAs). Primary aldosteronism is mainly caused by APAs or idiopathic hyperaldosteronism (IHA). We presume that APCCs are causing IHA and are precursors of APAs. However, the gene expression characteristics and especially the development of APCCs are not well understood. Objective: This study aimed to analyze the transcriptome of APCCs at single-cell resolution and infer the developmental trajectory. Methods: Single-cell RNA sequencing (scRNA-seq) of 2 adult adrenals was performed. Results: Immunohistochemical analyses confirmed the 2 adrenals had APCCs. scRNA-seq data of 2928 adrenal cells were obtained and 1765 adrenocortical cells were identified based on unsupervised clustering and the marker gene expression. The adrenocortical cells were divided into 6 clusters, of which 3 clusters (923 cells) were composed of APCC/ZG cells. By further subclustering, the APCC/ZG cells were divided into 3 clusters (clusters C1, C2, and C3), we finally identified APCC cluster (C3) and ZG cluster (C1). Cluster C2 seemed to be ZG-to-ZF transitional cells. RNA velocity analysis inferred the developmental direction from cluster ZG-cluster-C1 to APCC-cluster-C3. The scRNA-seq additionally revealed that many CYP11B2-positive cells were positive for CYP11B1 and/or CYP17A1, which were essential for cortisol but not for aldosterone production. Conclusions: Our results revealed the gene expression characteristics of APCC at single-cell resolution and show that some ZG cells remodel to APCC.

本文言語English
ページ(範囲)2439-2448
ページ数10
ジャーナルJournal of Clinical Endocrinology and Metabolism
107
9
DOI
出版ステータスPublished - 2022 9月 1

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 内分泌学
  • 臨床生化学
  • 生化学、医学

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