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Kogan, P.S.* ; Wirth, F.* ; Tomar, A. ; Darr, J. ; Teperino, R. ; Lahm, H.* ; Dreßen, M.* ; Puluca, N.* ; Zhang, Z.* ; Neb, I.* ; Beck, N.* ; Luzius, T.* ; de la Osa de la Rosa, L.* ; Gärtner, K. ; Hüls, C. ; Zeidler, R. ; Ramanujam, D.* ; Engelhardt, S.* ; Wenk, C.* ; Holdt, L.M.* ; Mononen, M.* ; Sahara, M.* ; Cleuziou, J.* ; Hörer, J.* ; Lange, R.* ; Krane, M.* ; Doppler, S.A.*

Uncovering the molecular identity of cardiosphere-derived cells (CDCs) by single-cell RNA sequencing.

Basic Res. Cardiol. 117:11 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Cardiosphere-derived cells (CDCs) generated from human cardiac biopsies have been shown to have disease-modifying bioactivity in clinical trials. Paradoxically, CDCs' cellular origin in the heart remains elusive. We studied the molecular identity of CDCs using single-cell RNA sequencing (sc-RNAseq) in comparison to cardiac non-myocyte and non-hematopoietic cells (cardiac fibroblasts/CFs, smooth muscle cells/SMCs and endothelial cells/ECs). We identified CDCs as a distinct and mitochondria-rich cell type that shared biological similarities with non-myocyte cells but not with cardiac progenitor cells derived from human-induced pluripotent stem cells. CXCL6 emerged as a new specific marker for CDCs. By analysis of sc-RNAseq data from human right atrial biopsies in comparison with CDCs we uncovered transcriptomic similarities between CDCs and CFs. By direct comparison of infant and adult CDC sc-RNAseq data, infant CDCs revealed GO-terms associated with cardiac development. To analyze the beneficial effects of CDCs (pro-angiogenic, anti-fibrotic, anti-apoptotic), we performed functional in vitro assays with CDC-derived extracellular vesicles (EVs). CDC EVs augmented in vitro angiogenesis and did not stimulate scarring. They also reduced the expression of pro-apoptotic Bax in NRCMs. In conclusion, CDCs were disclosed as mitochondria-rich cells with unique properties but also with similarities to right atrial CFs. CDCs displayed highly proliferative, secretory and immunomodulatory properties, characteristics that can also be found in activated or inflammatory cell types. By special culture conditions, CDCs earn some bioactivities, including angiogenic potential, which might modify disease in certain disorders.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cardiac Fibroblasts ; Cardiac Non-myocyte Cells ; Cardiosphere-derived Cells (cdcs) ; Extracellular Vesicles ; Right Atrial Biopsy ; Single-cell Rna Sequencing; Cardiac Progenitor Cells; Growth-factor; Extracellular Vesicles; Heart-failure; Stem-cells; Expression; Exosomes; Proliferation; Fibroblasts; Apoptosis
ISSN (print) / ISBN 0300-8428
e-ISSN 1435-1803
Zeitschrift Basic Research in Cardiology
Quellenangaben Band: 117, Heft: 1, Seiten: , Artikelnummer: 11 Supplement: ,
Verlag Springer
Verlagsort Tiergartenstrasse 17, D-69121 Heidelberg, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Research Unit Gene Vector (AGV)
Förderungen Deutsche Forschungsgemeinschaft