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

在单细胞分辨率下表征醛固酮生成细胞簇 (APCC)

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作者: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

Conclusions

Our results revealed the gene expression characteristics of APCC at single-cell resolution and show that some ZG cells remodel to APCC.

Methods

Single-cell RNA sequencing (scRNA-seq) of 2 adult adrenals was performed.

Objective

This study aimed to analyze the transcriptome of APCCs at single-cell resolution and infer the developmental trajectory.

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.

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