Discrimination of Dormant and Active Hematopoietic Stem Cells by G0 Marker Reveals Dormancy Regulation by Cytoplasmic Calcium

Quiescent hematopoietic stem cells (HSCs) are typically dormant, and only a few quiescent HSCs are active. The relationship between dormant and active HSCs remains unresolved. Here we generate a G(0) marker (G(0)M) mouse line that visualizes quiescent cells and identify a small population of active HSCs (G(0)M(low)), which are distinct from dormant HSCs (G(0)M(high)), within the conventional quiescent HSC fraction. Single-cell RNA-seq analyses show that the gene expression profiles of these populations are nearly identical but differ in their Cdk4/6 activity. Furthermore, high-throughput small-molecule screening reveals that high concentrations of cytoplasmic calcium ([Ca2+](c)) are linked to dormancy of HSCs. These findings indicate that G(0)M separates dormant and active adult HSCs, which are regulated by Cdk4/6 and [Ca2+](c). This G(0)M mouse line represents a useful resource for investigating physiologically important stem cell subpopulations.