Uncovering the molecular identity of cardiosphere-derived cells (CDCs) by single-cell RNA sequencing.
Cardiac fibroblasts
Cardiac non-myocyte cells
Cardiosphere-derived cells (CDCs)
Extracellular vesicles
Right atrial biopsy
Single-cell RNA sequencing
Journal
Basic research in cardiology
ISSN: 1435-1803
Titre abrégé: Basic Res Cardiol
Pays: Germany
ID NLM: 0360342
Informations de publication
Date de publication:
08 03 2022
08 03 2022
Historique:
received:
25
09
2020
accepted:
11
01
2022
revised:
11
01
2022
entrez:
8
3
2022
pubmed:
9
3
2022
medline:
6
5
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35258704
doi: 10.1007/s00395-022-00913-y
pii: 10.1007/s00395-022-00913-y
pmc: PMC8902493
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11Informations de copyright
© 2022. The Author(s).
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