A Survey for Human Tissue-Level Determinants of CAV1 Regulation and Function

Area of Science:

• Genetics and Molecular Biology
• Human Physiology
• Systems Biology

Background:

• Caveolin-1 (CAV1) is a protein-coding gene implicated in cancer, lipodystrophy, and cardiovascular diseases.
• While CAV1's response to mechanical and metabolic stimuli is known, its human physiological regulation remains unclear.

Purpose of the Study:

• To comprehensively explore the sources of variability in CAV1 transcriptional levels within human tissues.
• To establish a human-centric resource for understanding CAV1 regulation, avoiding inter-species comparisons.

Main Methods:

• Utilized extensive bulk and single-nuclei RNA-sequencing data from the Genotype-Tissue Expression (GTEx) consortium.
• Systematically analyzed human post-mortem tissue data to identify determinants of CAV1 expression.

Main Results:

• Cell type proportion emerged as a major determinant of CAV1 transcription across tissues.
• Donor physiological conditions (disease, end-of-life) showed tissue-specific influences on CAV1 levels.
• Chromatin modifiers (SMARCA2, PRC2), mechanobiology (TEAD4), immunity (RELA, STAT3), and metabolism (MYC, NRF1) regulators were identified.
• A strong correlation between CAV1 and immune cell infiltration was observed across tissues.

Conclusions:

• CAV1 regulation is complex, influenced by cellular composition and donor-specific factors in humans.
• CAV1 may serve as a marker and driver of tissue immune cell infiltration, highlighting its role in immunity.