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

• DOI: 10.1007/s00395-022-00913-y
• Publication Date: 2022-03-08T10:02:51Z
• Authors: Palgit-S. Kogan; Felix Wirth; Archana Tomar; Jonatan Darr; Raffaele Teperino; Harald Lahm; Martina Dreßen; Nazan Puluca; Zhong Zhang; Irina Neb; Nicole Beck; Tatjana Luzius; Luis de la Osa de...; Kathrin Gärtner; Corinna Hüls; Reinhard Zeidler; Deepak Ramanujam; Stefan Engelhardt; Catharina Wenk; Lesca M. Holdt; Mimmi Mononen; Makoto Sahara; Julie Cleuziou; Jürgen Hörer; Rüdiger Lange; Markus Krane; Stefanie A. Doppler
• Keywords: Cell type

Abstract Cardiosphere-derived cells (CDCs) generated from human cardiac biopsies have been shown to disease-modifying bioactivity in clinical trials. Paradoxically, CDCs’ cellular origin the heart remains elusive. We studied molecular identity of CDCs using single-cell RNA sequencing (sc-RNAseq) comparison non-myocyte and non-hematopoietic (cardiac fibroblasts/CFs, smooth muscle cells/SMCs endothelial cells/ECs). identified as a distinct mitochondria-rich cell type that shared biological similarities with but not progenitor derived human-induced pluripotent stem cells. CXCL6 emerged new specific marker for CDCs. By analysis sc-RNAseq data right atrial we uncovered transcriptomic between CFs. direct infant adult CDC data, revealed GO-terms associated development. To analyze beneficial effects (pro-angiogenic, anti-fibrotic, anti-apoptotic), performed functional vitro assays CDC-derived extracellular vesicles (EVs). EVs augmented angiogenesis did stimulate scarring. They also reduced expression pro-apoptotic Bax NRCMs. In conclusion, were disclosed unique properties displayed highly proliferative, secretory immunomodulatory properties, characteristics can be found activated or inflammatory types. special culture conditions, earn some bioactivities, including angiogenic potential, which might modify disease certain disorders.