Single-cell transcriptomic analysis reveals metabolic reprogramming and tumor microenvironment remodeling in...

Area of Science:

• Endocrinology
• Oncology
• Genomics

Background:

• Aldosterone-producing adenoma (APA) is a primary cause of primary aldosteronism.
• The cellular heterogeneity and underlying molecular mechanisms of APA remain largely uncharacterized.

Purpose of the Study:

• To comprehensively analyze the cellular landscape of APA using single-cell RNA sequencing.
• To identify key cellular pathways, biomarkers, and potential therapeutic targets in APA development.

Main Methods:

• Single-cell RNA sequencing was performed on adrenal tissues from three APA patients and three healthy controls.
• Bioinformatic analyses, including pseudotime analysis, were used to investigate cellular differentiation and pathway activation.

Main Results:

• Identification of CAPS+ zona glomerulosa (ZG)-like cells with metabolic reprogramming (lipogenesis, oxidative phosphorylation, mTOR signaling).
• Discovery of disrupted differentiation and aberrant gene expression (CYP11B1, CYP11B2, SULT2A1) in APA cells.
• Uncovering oncogenic pathway activation (Myc, Wnt), immune infiltration, angiogenic activity, and fibroblast-driven stromal remodeling (Hedgehog signaling).

Conclusions:

• This study provides a detailed single-cell atlas of APA, revealing critical tumorigenic mechanisms.
• Identified potential biomarkers (CAPS, VWF, UPK3B) and therapeutic targets (mTOR, Hedgehog/Wnt pathways) for precision medicine in adrenal tumors.