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

TL;DR

This survey explores how CAV1 gene expression is regulated in human tissues, identifying factors like cell type proportions and immune infiltration.

Contribution

The study provides a human-specific analysis of CAV1 regulation using post-mortem tissue data, avoiding inter-species comparisons.

Findings

Cell type proportion is a major determinant of CAV1 transcription levels across tissues.

Donor physiological conditions and end-of-life circumstances influence CAV1 levels in a tissue-specific manner.

CAV1 correlates with immune cell infiltration, suggesting a role in tissue immunity.

Abstract

CAV1 is a protein-coding gene linked to several disorders, including cancer, lipodystrophy, and cardiovascular diseases. While its ability to respond to various mechanical and metabolic stimuli has been documented, a comprehensive understanding of its physiological regulation in humans is lacking. We leveraged the comprehensiveness of human post-mortem tissue data from the Genotype-Tissue Expression (GTEx) consortium, systematically exploring the sources of variability in CAV1 transcriptional levels using extensive bulk and single-nuclei RNA-seq datasets. This human-centric approach, avoiding inter-species comparisons, constitutes a unique resource to explore CAV1 regulation within the complexity of human tissues. Notably, cell type proportion was identified as a major determinant of CAV1 transcription levels across tissues. Donor physiological conditions, including disease states and end-of-life circumstances, also exhibited a tissue-specific influence. Among primary upstream regulators associated with CAV1, chromatin modifiers stood out, especially SMARCA2, which showed a positive correlation across tissues, and PRC2 complexes, which exhibited tissue-specific correlation. Upstream regulatory networks determining CAV1 levels are also enriched for annotations such as mechanobiology (e.g., TEAD4), immunity (e.g., RELA and STAT3), and metabolism (e.g., MYC and NRF1). A remarkable observation was a strong correlation between CAV1 and the relative infiltration of immune cells across tissues, supporting a potential role for CAV1 as a marker and driver of tissue immune infiltration.

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