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 mouse line that visualizes quiescent cells. The G0 marker identifies a population of active HSCs (G0 markerlow) which are rare and distinct from dormant HSCs (G0 markerhigh) within the conventional quiescent HSC fraction. Single-cell RNA-sequencing 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 levels of basal cytoplasmic calcium (Ca2+) protected the dormancy of HSCs from cell cycle activation induced by calcium influx. These findings indicate that the G0 marker separates dormant and active adult HSCs, which are regulated by Cdk4/6 and Ca2+ levels. This G0 marker mouse line represents a useful new resource for investigating physiologically important stem cell subpopulations.
Fukushima, Tsuyoshi and Tanaka, Yosuke and Hamey, Fiona K. and Chang, Chih-Hsiang and Oki, Toshihiko and Umemoto, Terumasa and Asada, Shuhei and Hayashi, Yasutaka and Fujino, Takeshi and Yonezawa, Taishi and Takeda, Reina and Kawabata, Kimihito Cojin and Mikami, Keiko and Fukuyama, Tomofusa and Goyama, Susumu and Takizawa, Hitoshi and Ishihama, Yasushi and Honda, Hiroaki and Göttgens, Berthold and Kitamura, Toshio, Discrimination of Dormant and Active Hematopoietic Stem Cells by G
0 Markers Reveals Dormancy Regulation by Basal Cytoplasmic Calcium (January 8, 2019). Available at SSRN: https://ssrn.com/abstract=3312121 or http://dx.doi.org/10.2139/ssrn.3312121
This version of the paper has not been formally peer reviewed.
Subscribe to this free journal for more curated articles on this topic
FOLLOWERS
20
PAPERS
9,156
Feedback
Feedback to SSRN
If you need immediate assistance, call 877-SSRNHelp (877 777 6435) in the United States, or +1 212 448 2500 outside of the United States, 8:30AM to 6:00PM U.S. Eastern, Monday - Friday.