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 ([Ca 2+ ] 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 [Ca 2+ ] c .This G 0 M mouse line represents a useful resource for investigating physiologically important stem cell subpopulations.