Discrimination of Dormant and Active Hematopoietic Stem Cells by G<sub>0</sub> Marker Reveals Dormancy Regulation by Cytoplasmic Calcium.
Kawabata, Kimihito Cojin
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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 G<sub>0</sub> Marker Reveals Dormancy Regulation by Cytoplasmic Calcium.. Cell reports, 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 generated a G0 marker (G0M) mouse line that visualizes quiescent cells. G0M identifies 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 showed that the gene expression profiles of these populations were nearly identical, yet differed in their Cdk4/6 activity. Furthermore high-throughput small molecule screening revealed that high concentrations of cytoplasmic calcium ([Ca2+]c) were 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)
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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
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