Discrimination of Dormant and Active Hematopoietic Stem Cells by G0 Marker Reveals Dormancy Regulation by Cytoplasmic Calcium.
Authors
Fukushima, Tsuyoshi
Tanaka, Yosuke
Hamey, Fiona K
Chang, Chih-Hsiang
Oki, Toshihiko
Asada, Shuhei
Hayashi, Yasutaka
Fujino, Takeshi
Yonezawa, Taishi
Takeda, Reina
Kawabata, Kimihito Cojin
Fukuyama, Tomofusa
Umemoto, Terumasa
Takubo, Keiyo
Takizawa, Hitoshi
Goyama, Susumu
Ishihama, Yasushi
Honda, Hiroaki
Kitamura, Toshio
Publication Date
2019-12-17Journal Title
Cell Rep
ISSN
2211-1247
Publisher
Elsevier BV
Volume
29
Issue
12
Pages
4144-4158.e7
Language
eng
Type
Article
This Version
AM
Physical Medium
Print
Metadata
Show full item recordCitation
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
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.
Keywords
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
Sponsorship
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (079895/Z/06/Z)
Medical Research Council (MC_PC_12009)
Identifiers
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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http://www.rioxx.net/licenses/all-rights-reserved
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