title: Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation.
abstract: Hematopoietic stem cells (HSCs) maintain blood production. How often mouse HSCs divide and whether each HSC contributes simultaneously, sequentially, or repetitively to hematopoiesis remains to be determined. We track division of 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled HSC in vivo. We found that, in steady-state mice, bone marrow cells capable of reconstituting lifelong hematopoiesis are found within both fast-cycling (undergoing five or more divisions in 7 wk) and quiescent (undergoing zero divisions in 12-14 wk) lineage marker-negative c-Kit(+) Sca-1(+) populations. The contribution of each population to hematopoiesis can fluctuate with time, and cells with extensive proliferative history are prone to return to quiescence. Furthermore, injection of the bacterial component lipopolysaccharide increased the proliferation and self-renewal capacity of HSCs. These findings suggest a model in which all HSCs undergo dynamic and demand-adapted entry into and exit out of the cell cycle over time. This may facilitate a similar degree of turnover of the entire HSC pool at the end of life.
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Switzerland.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takizawa
authors.forename: Roland R
authors.initials: RR
authors.lastname: Regoes
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Boddupalli
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bonhoeffer
authors.forename: Markus G
authors.initials: MG
authors.lastname: Manz
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D005434:Flow Cytometry; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D013388:Succinimides
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D013388:Succinimides; D001973:Bromodeoxyuridine