Discrimination of Dormant and Active Hematopoietic Stem Cells by G0 Marker Reveals Dormancy Regulation by Cytoplasmic Calcium.
Hamey, Fiona K
Kawabata, Kimihito Cojin
MetadataShow full item record
Fukushima, T., Tanaka, Y., Hamey, F. K., Chang, C., Oki, T., Asada, S., Hayashi, Y., et al. (2019). Discrimination of Dormant and Active Hematopoietic Stem Cells by G0 Marker Reveals Dormancy Regulation by Cytoplasmic Calcium.. Cell Rep, 29 (12), 4144-4158.e7. https://doi.org/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.
Hematopoietic Stem Cells, Cytoplasm, Animals, Mice, Inbred C57BL, Mice, Calcium, Gene Expression Profiling, Cell Proliferation, Gene Expression Regulation, Female, Male, Gene Regulatory Networks, Single-Cell Analysis, Biomarkers, Cell Self Renewal, Resting Phase, Cell Cycle
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (079895/Z/06/Z)
Medical Research Council (MC_PC_12009)
External DOI: https://doi.org/10.1016/j.celrep.2019.11.061
This record's URL: https://www.repository.cam.ac.uk/handle/1810/299982
All rights reserved