The effect of bleeding on hematopoietic stem cell cycling and self-renewal.
Hematopoietic stem cells (HSCs) divide and give rise to more committed progenitors, which ultimately produce all lineages of blood cells. HSCs can be induced to enter the cell cycle in vitro and in vivo by stimulatory cytokines and in vivo by ablation of bone marrow (BM) cells with irradiation or chemotherapeutic agents. Although it has been postulated that rates of HSC proliferation increase with normal hematopoietic stresses, such as infection or hemorrhage, this hypothesis has never been directly tested. The ability to analyze HSCs prospectively by cell-surface phenotype c-kit(+), Thy1.1(lo), Sca-1(+), Linage(neg/lo) has allowed us to perform a detailed examination of the effects of bleeding on the cell cycle kinetics of HSCs. Our results demonstrate for the first time that HSCs in both the BM and the spleen proliferate and self-renew in response to tail-vein bleeding in mice. This response was suppressed when red blood cells, but not when white blood cells, were transferred after bleeding. Thus, regulators of HSC proliferation can sense and respond to red blood cell levels.
Cheshier
Samuel H
SH
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Prohaska
Susan S
SS
Weissman
Irving L
IL
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001789:Blood Group Antigens / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D015415:Biomarkers; D001789:Blood Group Antigens; D016177:Macrophage-1 Antigen; C489122:TER-119 antigen, mouse; D004921:Erythropoietin; D004247:DNA