Single-nucleus RNA sequencing of aldosterone-producing adenomas revealed intratumoral heterogeneity and identified 2 distinct cell fates, including one specialized in aldosterone synthesis.
Observational (n=5)
Single-nucleus RNA sequencing reveals significant intratumoral heterogeneity and distinct cellular differentiation pathways in aldosterone-producing adenomas.
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: 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: -mutated APAs provides the postulation that a heterogeneous process of cellular differentiation was implicated in the pathophysiological mechanisms underlying APA tumors.
Murakami et al. (Thu,) conducted a observational in Aldosterone-producing adenoma (n=5). Aldosterone-producing adenoma vs. Nonfunctional adenomas was evaluated on Intratumoral heterogeneity and cell populations. Single-nucleus RNA sequencing of aldosterone-producing adenomas revealed intratumoral heterogeneity and identified 2 distinct cell fates, including one specialized in aldosterone synthesis.
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