Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair.
Details
Serval ID
serval:BIB_CCF66F1175CB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair.
Journal
Cell
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
135
Number
6
Pages
1118-1129
Language
english
Abstract
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.
Keywords
Adult Stem Cells/cytology, Adult Stem Cells/physiology, Animals, Antigens, Differentiation/metabolism, Bone Marrow/physiology, Fluorouracil/metabolism, Green Fluorescent Proteins, Hematopoietic Stem Cells/cytology, Hematopoietic Stem Cells/physiology, Homeostasis, Mice, Mice, Transgenic, Uridine/analogs & derivatives, Uridine/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2009 23:14
Last modification date
20/08/2019 16:47