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Related Experiment Video

Updated: Jan 22, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Integrated Transcriptomics Reveals Evolutionary Trajectories and Cell Density-Dependent Mechanisms in

Zhuolun Sun1, Changying Jing2, Martina Tetti1

  • 1Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, 80336, Munich, Germany.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|January 21, 2026
PubMed
Summary
This summary is machine-generated.

Aldosterone-producing adenomas (APAs) and micronodules (APMs) show significant molecular differences. This study reveals distinct tumor evolution paths and cellular states, impacting primary aldosteronism understanding.

Keywords:
Aldosterone‐producing adenomasevolutionary trajectorysingle‐cell/nucleus transcriptomicsspatial transcriptomicstumor microenvironment

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Area of Science:

  • Endocrinology
  • Oncology
  • Genomics

Background:

  • Aldosterone-producing adenomas (APAs) and micronodules (APMs) cause primary aldosteronism, a common secondary hypertension.
  • Understanding the molecular basis of APA and APM development is crucial for effective treatment.

Purpose of the Study:

  • To investigate the heterogeneity and molecular pathogenesis of APAs and APMs.
  • To elucidate the evolutionary trajectories and cellular states within APAs.

Main Methods:

  • Integrated single-cell/nucleus and spatial transcriptomics.
  • Pseudotime analyses to model tumor progression.
  • In vitro studies using human adrenal cells.

Main Results:

  • APAs and APMs exhibit substantial transcriptional heterogeneity and an immunosuppressive tumor microenvironment in APAs.
  • Two distinct evolutionary paths for APAs were identified: direct and stepwise (via APMs).
  • KCNJ5-mutated APAs show progenitor-like and mature cellular states, with shifts in oxidative stress and focal adhesion pathways, including ferroptosis.

Conclusions:

  • The study reveals complex molecular alterations and transcriptional diversity in APAs and APMs.
  • Findings enhance understanding of APA pathogenesis and identify TAZ activation's role in ferroptosis sensitivity.
  • This research provides insights into the molecular mechanisms driving primary aldosteronism.