Expression of Coxsackievirus and Adenovirus Receptor Separates Hematopoietic and Cardiac Progenitor Cells in Fetal Liver Kinase 1-Expressing Mesoderm

摘要

In developing embryos or in vitro differentiation cultures using pluripotent stem cells (PSCs), such as embryonic stem cells and induced pluripotent stem cells, fetal liver kinase 1 (Flk1)-expressing mesodermal cells are thought to be a heterogeneous population that includes hematopoietic progenitors, endothelial progenitors, and cardiac progenitors. However, information on cell surface markers for separating these progenitors in Flk1(+) cells is currently limited. In the present study, we show that distinct types of progenitor cells in Flk1(+) cells could be separated according to the expression of coxsackievirus and adenovirus receptor (CAR, also known as CXADR), a tight junction component molecule. We found that mouse and human PSC- and mouse embryo-derived Flk1(+) cells could be subdivided into Flk1(+)CAR(+) cells and Flk1(+)CAR(-) cells. The progenitor cells with cardiac potential were almost entirely restricted to Flkl(+)CAR(+) cells, and Flk1(+)CAR(-) cells efficiently differentiated into hematopoietic cells. Endothelial differentiation potential was observed in both populations. Furthermore, from the expression of CAR, Flk1, and platelet-derived growth factor receptor-alpha (PDGFR alpha), Flk1(+) cells could be separated into three populations (Flk1(+)PDGFR alpha(-)CAR(-) cells, Flk1(+)PDGFR alpha(-)CAR(+) cells, and Flk1(+)PDGFR alpha(+)CAR(+) cells). Flk1(+)PDGFR alpha(+) cells and Flk1(+)PDGFR alpha(-) cells have been reported as cardiac and hematopoietic progenitor cells, respectively. We identified a novel population (Flk1(+)PDGFR alpha(-)CAR(+) cells) with the potential to differentiate into not only hematopoietic cells and endothelial cells but also cardiomyocytes. Our findings indicate that CAR would be a novel and prominent marker for separating PSC- and embryo-derived Flk1(+) mesodermal cells with distinct differentiation potentials.