Long-term adaptation to hypoxia preserves hematopoietic stem cell function.
Molecular oxygen sustains aerobic life, but it also serves as the substrate for oxidative stress, which has been associated with the pathogenesis of disease and with aging. Compared with mice housed in normoxia (21% O2), reducing ambient oxygen to 10% O2 (hypoxia) resulted in increased hematopoietic stem cell (HSC) function as measured by bone marrow (BM) cell engraftment onto lethally irradiated recipients. The number of BM c-Kit(+)Sca-1(+)Lin(-) (KSL) cells as well as the number of cells with other hematopoietic stem and progenitor cell markers were increased in hypoxia mice, whereas the BM cells' colony-forming capacity remained unchanged. KSL cells from hypoxia mice showed a decreased level of oxidative stress and increased expression of transcription factor Gata1 and cytokine receptor c-Mpl, consistent with the observations of increased erythropoiesis and enhanced HSC engraftment. These observations demonstrate the benefit of a hypoxic HSC niche and suggest that hypoxic conditions can be further optimized to preserve stem cell integrity in vivo.
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: chenji@nhlbi.nih.gov.
Jichun
J
Chen
Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Ju-Gyeong
JG
Kang
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Keyvan
K
Keyvanfar
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Neal S
NS
Young
Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: hwangp@mail.nih.gov.
Paul M
PM
Hwang
D000220:Adaptation, Biological / Q000235:genetics; D000818:Animals; D003114:Colony-Forming Units Assay; D020869:Gene Expression Profiling; D006085:Graft Survival; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D018384:Oxidative Stress; D013997:Time Factors