Single-cell transcriptomics reveal extracellular vesicles secretion with a cardiomyocyte proteostasis signature during pathological remodeling

2023 | journal article. A publication with affiliation to the University of Göttingen.

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​Single-cell transcriptomics reveal extracellular vesicles secretion with a cardiomyocyte proteostasis signature during pathological remodeling​
Schoger, E.; Bleckwedel, F.; Germena, G.; Rocha, C.; Tucholla, P.; Sobitov, I. & Möbius, W.  et al.​ (2023) 
Communications Biology6(1).​ DOI: 

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Schoger, Eric; Bleckwedel, Federico; Germena, Giulia; Rocha, Cheila; Tucholla, Petra; Sobitov, Izzatullo; Möbius, Wiebke ; Sitte, Maren; Lenz, Christof ; Samak, Mostafa; Zelarayán, Laura C. 
Abstract Aberrant Wnt activation has been reported in failing cardiomyocytes. Here we present single cell transcriptome profiling of hearts with inducible cardiomyocyte-specific Wnt activation (β-cat Δex3 ) 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 β-cat Δex3 mice. A proteomic analysis of in vivo cardiac derived EVs from β-cat Δex3 hearts has identified differentially enriched proteins involving 20 S proteasome constitutes, protein quality control (PQC), chaperones and associated cardiac proteins including α-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 be used for monitoring cellular remodeling in vivo with a possible diagnostic and prognostic role in the future.
Issue Date
Communications Biology 
EXC 2067: Multiscale Bioimaging 
SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz 
SFB 1002 | C07: Kardiomyozyten Wnt/β-catenin Komplex Aktivität im pathologischen Herz-Remodeling - als gewebespezifischer therapeutischer Ansatz 
SFB 1002 | INF: Unterstützung der SFB 1002 Forschungsdatenintegration, -visualisierung und -nachnutzung 
Deutsches Primatenzentrum 
Working Group
RG Möbius 
RG Zelarayán-Behrend (Developmental Pharmacology) 
RG Hinkel 
RG Lenz 
Open-Access-Publikationsfonds 2023



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