Single-Nucleus Analysis Reveals Tumor Heterogeneity of Aldosterone-Producing Adenoma

被引：4

作者：

Murakami, Masanori ^{[1
]}

Hara, Kazunari ^{[1
]}

Ikeda, Kenji ^{[1
]}

Horino, Masato ^{[1
]}

Okazaki, Rei ^{[1
]}

Niitsu, Yoshihiro ^{[1
]}

Takeuchi, Akira ^{[1
]}

Aoki, Jun ^{[1
]}

Shiba, Kumiko ^{[1
,2
]}

Tsujimoto, Kazutaka ^{[1
]}

Komiya, Chikara ^{[1
]}

Nakamura, Yuki ^{[3
]}

Kurata, Morito ^{[4
]}

Akashi, Takumi ^{[5
,6
]}

Fujii, Yasuhisa ^{[3
]}

Yamada, Tetsuya ^{[1
]}

机构：

[1] Tokyo Med & Dent Univ, Dept Mol Endocrinol & Metab, Grad Sch Med & Dent Sci, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138510, Japan

[2] Tokyo Med & Dent Univ, Ctr Personalized Med Hlth Aging, Tokyo, Japan

[3] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Urol, Tokyo, Japan

[4] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Comprehens Pathol, Tokyo, Japan

[5] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Diagnost Pathol, Tokyo, Japan

[6] Tokyo Med & Dent Univ Hosp, Div Surg Pathol, Tokyo, Japan

来源：

HYPERTENSION | 2024年 / 81卷 / 02期

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

adrenocortical adenoma; aldosterone; hyperaldosteronism; sequence analysis; RNA; transcriptome; SOMATIC MUTATIONS; PREVALENCE; EXPRESSION; DIAGNOSIS; SOCIETY; ATP1A1;

D O I：

10.1161/HYPERTENSIONAHA.123.21446

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

BACKGROUND:Recent advances in omics techniques have allowed detailed genetic characterization of aldosterone-producing adenoma (APA). The pathogenesis of APA is characterized by tumorigenesis-associated aldosterone synthesis. The pathophysiological intricacies of APAs have not yet been elucidated at the level of individual cells. Therefore, a single-cell level analysis is speculated to be valuable in studying the differentiation process of APA.METHODS:We conducted single-nucleus RNA sequencing of APAs with KCNJ5 mutation and nonfunctional adenomas obtained from 3 and 2 patients, respectively.RESULTS:The single-nucleus RNA sequencing revealed the intratumoral heterogeneity of APA and identified cell populations consisting of a shared cluster of nonfunctional adenoma and APA. In addition, we extracted 2 cell fates in APA and obtained a cell population specialized in aldosterone synthesis. Genes related to ribosomes and neurodegenerative diseases were upregulated in 1 of these fates, whereas those related to the regulation of glycolysis were upregulated in the other fate. Furthermore, the total RNA reads in the nucleus were higher in hormonally activated clusters, indicating a marked activation of transcription per cell.CONCLUSIONS:The single-nucleus RNA sequencing revealed intratumoral heterogeneity of APA with KCNJ5 mutation. The observation of 2 cell fates in KCNJ5-mutated APAs provides the postulation that a heterogeneous process of cellular differentiation was implicated in the pathophysiological mechanisms underlying APA tumors.

引用

页码：361 / 371

页数：11

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