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

Summary: 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 G0 marker (G0M) mouse line that visualizes quiescent cells and identify a small population of active HSCs (G0Mlow), which are distinct from dormant HSCs (G0Mhigh), 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 G0M separates dormant and active adult HSCs, which are regulated by Cdk4/6 and [Ca2+]c. This G0M mouse line represents a useful resource for investigating physiologically important stem cell subpopulations.: Fukushima et al. show that G0 marker (G0M) 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. Keywords: hematopoietic stem cell, HSC, cell cycle, G0 phase, p27, dormancy, CDK, calcium

Abstract licence: CC BY-NC

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