title: Chronic TLR signaling impairs the long-term repopulating potential of hematopoietic stem cells of wild type but not Id1 deficient mice.
abstract: Hematopoietic stem cells (HSCs) maintain life-long blood supply but are inevitably exposed to various inflammatory stimuli, which have been shown to be harmful for HSC integrity but the mediators of the deleterious effects have not been fully identified. Here, we show that daily injection of mice with 1 µg of LPS for 30 days triggers a storm of inflammatory cytokines. LPS injection also stimulated the transcription of the Id1 gene in HSCs in vivo but not in vitro, suggesting an indirect effect. To determine the effects of LPS treatment on HSC function and to evaluate the significance of Id1 expression, we assess the repopulating potential of wild type and Id1 deficient mice, which were subjected to a 30 day regimen of LPS treatment. We found that LPS caused dramatic reduction in the long-term but not short-term repopulating activity of wild type but not Id1 deficient HSC. This treatment also led to increases in HSC counts, decreases in BrdU-label retention and disturbance of quiescence detected by Ki67 staining in wild type but not Id1 deficient mice. Together, it appears that Id1, at least in part, plays a role in LPS-induced damage of HSC integrity.
authors: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
authors: Ying
authors: Y
authors: Zhao
authors: Flora
authors: F
authors: Ling
authors: Hong-Cheng
authors: HC
authors: Wang
authors: Xiao-Hong
authors: XH
authors: Sun
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D016207:Cytokines / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D051798:Inhibitor of Differentiation Protein 1 / Q000172:deficiency* / Q000235:genetics; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017931:DNA Primers; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
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