THY-1 Receptor Expression Differentiates Cardiosphere-Derived Cells with Divergent Cardiogenic Differentiation Potential

Summary Despite over a decade of intense research, the identity and differentiation potential of human adult cardiac progenitor cells (aCPC) remains controversial. Cardiospheres have been proposed as a means to expand aCPCs in vitro, but the identity of the progenitor cell within these 3D structures is unknown. We show that clones derived from cardiospheres could be subdivided based on expression of thymocyte differentiation antigen 1 (THY-1/CD90) into two distinct populations that exhibit divergent cardiac differentiation potential. One population, which is CD90+, expressed markers consistent with a mesenchymal/myofibroblast cell. The second clone type was CD90− and could form mature, functional myocytes with sarcomeres albeit at a very low rate. These two populations of cardiogenic clones displayed distinct cell surface markers and unique transcriptomes. Our study suggests that a rare aCPC exists in cardiospheres along with a mesenchymal/myofibroblast cell, which demonstrates incomplete cardiac myocyte differentiation.
Highlights • The majority of human adult CS-derived cardiomyocytes do not form sarcomeres • There is little overlap between the C-KIT and NKX2.5 cell populations in human CS • CD90 distinguishes two populations that exhibit divergent cardiogenic potential • CD90neg CS cells can differentiate into mature cardiomyocytes at a very low rate
Cardiospheres (CSs) have been reported to contain an adult cardiac progenitor cell (aCPC) with multilineage differentiation potential. MacLellan and colleagues show that CS-derived cells differentiate robustly into endothelial and smooth muscle cells but predominantly form immature cardiomyocytes. CD90 expression distinguishes CS-derived cells with a mesenchymal cell phenotype with incomplete cardiomyocyte differentiation (CD90+) and a CD90− population that could give rise to mature cardiomyocytes, although infrequently.