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)
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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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
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
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Language
english
Publication Year
2022
Prepublished in Year
HGF-reported in Year
2022
ISSN (print) / ISBN
0300-8428
e-ISSN
1435-1803
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Volume: 117,
Issue: 1,
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Article Number: 11
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Springer
Publishing Place
Tiergartenstrasse 17, D-69121 Heidelberg, Germany
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Reviewing status
Peer reviewed
POF-Topic(s)
90000 - German Center for Diabetes Research
30203 - Molecular Targets and Therapies
Research field(s)
Genetics and Epidemiology
Immune Response and Infection
PSP Element(s)
G-501900-069
G-501501-001
G-501500-001
Grants
Deutsche Forschungsgemeinschaft
Copyright
Erfassungsdatum
2022-05-02