西亚试剂：Hematopoietic Stem Cells Reversibly Switch from Dormancy to

发布时间：2025-09-10

Hematopoietic Stem Cells Reversibly Switch from Dormancy to Self-Renewal during Homeostasis and Repair

Anne Wilson3,Elisa Laurenti1,8,Gabriela Oser1,8,Richard C. van der Wath4,8,William Blanco-Bose1,8,Maike Jaworski1,Sandra Offner1,Cyrille F. Dunant6,Leonid Eshkind5,Ernesto Bockamp5,Pietro Lió4,H. Robson MacDonald3andAndreas Trumpp1,2,7,,

1 Ecole Polytechnique Fédérale de Lausanne (EPFL), Swiss Institute for Experimental Cancer Research (ISREC), School of Life Science, CH-1015 Lausanne, Switzerland
2 Divison of Cell Biology, Deutsches Krebsforschungszentrum (DKFZ), Division of Cell Biology, DKFZ-ZMBH Alliance,Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
3 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
4 Computer Laboratory, University of Cambridge, Cambridge CB3 0FD, UK
5 Institute for Toxicology, Laboratory of Molecular Mouse Genetics, Johannes Gutenberg-University Mainz, 55113 Mainz, Germany
6 LMC-IMX and Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
7 Heidelberg Institute for Stem Cell Technologies and Experimental Medicine (HI-STEM), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
8 These authors contributed equally to this work

Bone marrow hematopoietic stem cells (HSCs) are crucial to maintain lifelong production of all blood cells. Although HSCs divide infrequently, it is thought that the entire HSC pool turns over every few weeks, suggesting that HSCs regularly enter and exit cell cycle. Here, we combine flow cytometry with label-retaining assays (BrdU and histone H2B-GFP) to identify a population of dormant mouse HSCs (d-HSCs) within the linSca1+cKit+CD150+CD48CD34 population. Computational modeling suggests that d-HSCs divide about every 145 days, or five times per lifetime. d-HSCs harbor the vast majority of multilineage long-term self-renewal activity. While they form a silent reservoir of the most potent HSCs during homeostasis, they are efficiently activated to self-renew in response to bone marrow injury or G-CSF stimulation. After re-establishment of homeostasis, activated HSCs return to dormancy, suggesting that HSCs are not stochastically entering the cell cycle but reversibly switch from dormancy to self-renewal under conditions of hematopoietic stress.

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