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

Cell Rep. 2019 Dec 17;29(12):4144-4158.e7. doi: 10.1016/j.celrep.2019.11.061.


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.

Keywords: CDK; G(0) phase; HSC; calcium; cell cycle; dormancy; hematopoietic stem cell; p27.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism*
  • Calcium / metabolism*
  • Cell Proliferation
  • Cell Self Renewal*
  • Cytoplasm / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Resting Phase, Cell Cycle*
  • Single-Cell Analysis


  • Biomarkers
  • Calcium