Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair.
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 lin(-)Sca1+cKit+CD150+CD48(-)CD34(-) 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.
Wilson
Anne
A
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland.
Laurenti
Elisa
E
Oser
Gabriela
G
van der Wath
Richard C
RC
Blanco-Bose
William
W
Jaworski
Maike
M
Offner
Sandra
S
Dunant
Cyrille F
CF
Eshkind
Leonid
L
Bockamp
Ernesto
E
Lió
Pietro
P
Macdonald
H Robson
HR
Trumpp
Andreas
A
D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001853:Bone Marrow / Q000502:physiology; D001976:Bromouracil / Q000031:analogs & derivatives; D005472:Fluorouracil / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006706:Homeostasis; D051379:Mice; D008822:Mice, Transgenic; D014529:Uridine / Q000031:analogs & derivatives / Q000378:metabolism
D000943:Antigens, Differentiation; D049452:Green Fluorescent Proteins; D001976:Bromouracil; C006824:5-bromouridine; D005472:Fluorouracil; D014529:Uridine