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Here we present single cell transcriptome profiling of hearts with inducible cardiomyocyte-specific Wnt activation (\u03b2-cat<jats:sup>\u0394ex3<\/jats:sup>) as well as with compensatory and failing hypertrophic remodeling. We show that functional enrichment analysis points to an involvement of extracellular vesicles (EVs) related processes in hearts of \u03b2-cat<jats:sup>\u0394ex3<\/jats:sup> mice. A proteomic analysis of in vivo cardiac derived EVs from \u03b2-cat<jats:sup>\u0394ex3<\/jats:sup> hearts has identified differentially enriched proteins involving 20\u2009S proteasome constitutes, protein quality control (PQC), chaperones and associated cardiac proteins including \u03b1-Crystallin B (CRYAB) and sarcomeric components. The hypertrophic model confirms that cardiomyocytes reacted with an acute early transcriptional upregulation of exosome biogenesis processes and chaperones transcripts including CRYAB, which is ameliorated in advanced remodeling. Finally, human induced pluripotent stem cells (iPSC)-derived cardiomyocytes subjected to pharmacological Wnt activation recapitulated the increased expression of exosomal markers, CRYAB accumulation and increased PQC signaling. These findings reveal that secretion of EVs with a proteostasis signature contributes to early patho-physiological adaptation of cardiomyocytes, which may serve as a read-out of disease progression and can\u00a0be used for monitoring cellular remodeling in vivo with a possible diagnostic and prognostic role in the future.<\/jats:p>","DOI":"10.1038\/s42003-022-04402-9","type":"journal-article","created":{"date-parts":[[2023,1,21]],"date-time":"2023-01-21T08:02:53Z","timestamp":1674288173000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Single-cell transcriptomics reveal extracellular vesicles secretion with a cardiomyocyte proteostasis signature during pathological remodeling"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-9828","authenticated-orcid":false,"given":"Eric","family":"Schoger","sequence":"first","affiliation":[]},{"given":"Federico","family":"Bleckwedel","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7005-4272","authenticated-orcid":false,"given":"Giulia","family":"Germena","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-9405","authenticated-orcid":false,"given":"Cheila","family":"Rocha","sequence":"additional","affiliation":[]},{"given":"Petra","family":"Tucholla","sequence":"additional","affiliation":[]},{"given":"Izzatullo","family":"Sobitov","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2902-7165","authenticated-orcid":false,"given":"Wiebke","family":"M\u00f6bius","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-2604","authenticated-orcid":false,"given":"Maren","family":"Sitte","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0946-8166","authenticated-orcid":false,"given":"Christof","family":"Lenz","sequence":"additional","affiliation":[]},{"given":"Mostafa","family":"Samak","sequence":"additional","affiliation":[]},{"given":"Rabea","family":"Hinkel","sequence":"additional","affiliation":[]},{"given":"Zolt\u00e1n V.","family":"Varga","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2036-8665","authenticated-orcid":false,"given":"Zolt\u00e1n","family":"Giricz","sequence":"additional","affiliation":[]},{"given":"Gabriela","family":"Salinas","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8939-5664","authenticated-orcid":false,"given":"Julia C.","family":"Gross","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9001-0346","authenticated-orcid":false,"given":"Laura C.","family":"Zelaray\u00e1n","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,1,21]]},"reference":[{"key":"4402_CR1","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1161\/HYPERTENSIONAHA.118.10845","volume":"72","author":"S Kumar","year":"2018","unstructured":"Kumar, S. et al. 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