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Director of the National Institutes of Health","award":["CEX2020-001041-S"],"award-info":[{"award-number":["CEX2020-001041-S"]}]},{"name":"Common Fund of the Office of the Director of the National Institutes of Health","award":["MICIN\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["MICIN\/AEI\/10.13039\/501100011033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms26083789","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T04:16:21Z","timestamp":1744863381000},"page":"3789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Survey for Human Tissue-Level Determinants of CAV1 Regulation and Function"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6698-7328","authenticated-orcid":false,"given":"V\u00edctor","family":"Jim\u00e9nez-Jim\u00e9nez","sequence":"first","affiliation":[{"name":"Mechanoadaptation & Caveolae Biology Lab, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain"},{"name":"Bioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain"},{"name":"Department of Quantitative Methods, CUNEF Universidad, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-1664","authenticated-orcid":false,"given":"F\u00e1tima","family":"S\u00e1nchez-Cabo","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2071-1243","authenticated-orcid":false,"given":"Martin A.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT 06510, USA"},{"name":"Department of Cell Biology, Yale University, New Haven, CT 06510, USA"},{"name":"Department of Biomedical Engineering, Yale University, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5287-1420","authenticated-orcid":false,"given":"Miguel","family":"S\u00e1nchez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Mechanoadaptation & Caveolae Biology Lab, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain"},{"name":"Cell Compartmentalization, Homeostasis and Inflammation Lab, Department of Metabolic and Immunity Diseases, Instituto de Investigaciones Biom\u00e9dicas Sols-Morreale, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9077-391X","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"del Pozo","sequence":"additional","affiliation":[{"name":"Mechanoadaptation & Caveolae Biology Lab, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/nrm3512","article-title":"Caveolae as plasma membrane sensors, protectors and organizers","volume":"14","author":"Parton","year":"2013","journal-title":"Nat. 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