Multiomics analysis unveils the cellular ecosystem with clinical relevance in aldosterone-producing adenomas with <i>KCNJ5</i> mutations.

ABSTRACT: Aldosterone-producing adenomas (APA), a major endocrine tumor and leading subtype of primary aldosteronism, cause secondary hypertension with high cardiometabolic risks. Despite potentially producing multiple steroid hormones, detailed cellular mechanisms in APA remain insufficiently studied. Our multiomics analysis focusing on APA with KCNJ5 mutations, which represent the most common genetic form, revealed marked cellular heterogeneity. Tumor cell reprogramming initiated from stress-responsive cells to aldosterone-producing or cortisol-producing cells, with the latter progressing to proliferative stromal-like cells. These cell subtypes showed spatial segregation, and APA exhibited genomic intratumor heterogeneity. Among the nonparenchymal cells, lipid-associated macrophages, which

SUBMITTER: Yokomoto-Umakoshi M 

PROVIDER: S-EPMC11892633 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature