Exploring heterogeneity of tumor immune cells and adrenal cells in aldosterone-producing adenomas using single-cell RNA-seq and investigating differences by sex

Jing, Huang; Qin, Fei; Lai, Xiaomei; Yang, Tingting; Yu, Jie; Wei, Chaoping; Wei, Lixia; Li, Jianling

doi:10.1016/j.heliyon.2023.e14357

Cited by 2 publications

(2 citation statements)

References 37 publications

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“…Moreover, the other study using single-cell RNA sequencing for APA tissues compared pathway analyses in 2 female cases and 1 male case with unknown somatic mutations. 20 In this study, we compared APA cases with the same somatic mutation in 3 female patients to NFA cases, resulting in a more focused analysis that enabled us to dissect a pathogenesis of APA with a typical phenotype and genotype.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12][13][14][15][16][17] Recently, single-cell RNA sequencing technology, which examines the cellular composition and features, and functions of tumor cells, has been increasingly applied to study the occurrence and development of diseases at the cellular level. 18 However, reports on the use of single-cell RNA sequencing or single-nucleus RNA sequencing (snRNA-seq) in studying the adrenal tissue, such as the identification of aldosterone-producing cell clusters at the single-cell level in the examination of normal human adrenal tissue, 19 a thorough investigation of immune cells in the analysis of APA tissue, 20 and the clustering analysis to identify the localization of diseasespecific genes in peritumoral adrenal cortex tissues, 21 are limited. We used snRNA-seq to analyze the APA tissue at the level of nucleus extracted from frozen specimens 22 for the first time.…”

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confidence: 99%

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

Murakami,

Hara,

Ikeda

et al. 2024

Hypertension

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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.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Murakami,

Hara,

Ikeda

et al. 2024

Hypertension

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Identification and Analysis of Sex-Biased MicroRNAs in Human Diseases

Zhong,

Cui,

Cui

2023

Genes

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It is well known that significant differences exist between males and females in both physiology and disease. Thus, it is important to identify and analyze sex-biased miRNAs. However, previous studies investigating sex differences in miRNA expression have predominantly focused on healthy individuals or restricted their analysis to a single disease. Therefore, it is necessary to comprehensively identify and analyze the sex-biased miRNAs in diseases. For this purpose, in this study, we first identified the miRNAs showing sex-biased expression between males and females in diseases based on a number of miRNA expression datasets. Then, we performed a bioinformatics analysis for these sex-biased miRNAs. Notably, our findings revealed that women exhibit a greater number of conserved miRNAs that are highly expressed compared to men, and these miRNAs are implicated in a broader spectrum of diseases. Additionally, we explored the enriched transcription factors, functions, and diseases associated with these sex-biased miRNAs using the miRNA set enrichment analysis tool TAM 2.0. The insights gained from this study could carry implications for endeavors such as precision medicine and possibly pave the way for more targeted and tailored approaches to disease management.

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Exploring heterogeneity of tumor immune cells and adrenal cells in aldosterone-producing adenomas using single-cell RNA-seq and investigating differences by sex

Cited by 2 publications

References 37 publications

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

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

Identification and Analysis of Sex-Biased MicroRNAs in Human Diseases

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