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Several molecular pathways have been implicated in VEGF-induced hyperpermeability, including binding of the VEGF-activated tyrosine kinase receptor VEGFR2 by the T-cell specific adaptor (TSAd) to recruit a SRC family kinase to induce junction opening between vascular endothelial cells (ECs). Inconsistent with a universal role for TSAd in permeability signalling, immunostaining approaches previously reported TSAd only in dermal and kidney vasculature. To address this discrepancy, we have mined publicly available omics data for expression of TSAd and other permeability-relevant signal transducers in multiple organs affected by VEGF-induced vascular permeability. Unexpectedly, TSAd transcripts were largely absent from EC single cell RNAseq data, whereas transcripts for other permeability-relevant signal transducers were detected readily. TSAd transcripts were also lacking from half of the EC bulk RNAseq datasets examined, and in the remaining datasets appeared at low levels concordant with models of leaky transcription. Epigenomic EC data located the TSAd promoter to closed chromatin in ECs, and mass spectrometry-derived EC proteomes typically lacked TSAd. By suggesting that TSAd is not actively expressed in ECs, our findings imply that TSAd is likely not critical for linking VEGFR2 to downstream signal transducers for EC junction opening.<\/jats:p>","DOI":"10.1007\/s10456-025-09971-x","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T13:05:31Z","timestamp":1741871131000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Endothelial transcriptomic, epigenomic and proteomic data challenge the proposed role for TSAd in vascular permeability"],"prefix":"10.1007","volume":"28","author":[{"given":"James T.","family":"Brash","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Diez-Pinel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Rinaldi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael F. 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