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. • G 0 marker (G 0 M) discriminates between dormant (G 0 M^high) and active (G 0 M^low) HSCs • Active (G 0 M^low) HSCs exhibit higher CDK4/6 activity than dormant (G 0 M^high) HSCs • [Ca²⁺] c ^high HSCs have higher bone marrow reconstitution ability than [Ca²⁺] c ^low HSCs • Upregulation of [Ca²⁺] c enhances bone marrow reconstitution ability of HSCs Fukushima et al. show that G 0 marker (G 0 M) discriminates between dormant and active HSCs within the conventional quiescent HSC fraction. Small-molecule screening reveals that high [Ca²⁺] c is linked to dormancy of HSCs. Moreover, upregulation of [Ca²⁺] c by thapsigargin enhances the bone marrow reconstitution ability of HSCs. [ABSTRACT FROM AUTHOR]