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

January 6 2020

Terunmasa Umemoto, Hitoshi Takizawa

Paper information

Tsuyoshi Fukushima, Yosuke Tanaka, Fiona K. Hamey, Chih-Hsiang Chang, Toshihiko Oki, Shuhei Asada, Yasutaka Hayashi, Takeshi Fujino, Taishi Yonezawa, Reina Takeda, Kimihito Cojin Kawabata,　Tomofusa Fukuyama, Terumasa Umemoto,　Keiyo Takubo, Hitoshi Takizawa, Susumu Goyama, Yasushi Ishihama, Hiroaki Honda, Berthold Gottgens, and Toshio Kitamura

Discrimination of Dormant and Active Hematopoietic Stem Cells by G₀ Marker Reveals Dormancy Regulation by Cytoplasmic Calcium
Cell Rep. 2019  doi: 10.1016/j.celrep.2019.11.061

Highlights

• G₀ marker (G₀M) discriminates between dormant (G₀M^high) and active (G₀M^low) HSCs.
• Active (G0Mlow) HSCs exhibit higher CDK4/6 activity than dormant (G0Mhigh) 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

Abstract

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.