Chronic TLR signaling impairs the long-term repopulating potential of hematopoietic stem cells of wild type but not Id1 deficient mice.
Chronic TLR signaling impairs the long-term repopulating potential of hematopoietic stem cells of wild type but not Id1 deficient mice.
复制标题
DOI：
10.1371/journal.pone.0055552
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sun XH
中科院分区：
文献类型：
--
作者：
Zhao Y;Ling F;Wang HC;Sun XH
造血干细胞（HSC）维持终身血液供应，但不可避免地暴露于各种炎症刺激，这已被证明对HSC的完整性有害，但有害影响的介质尚未完全确定。在这里，我们发现每天给小鼠注射1微克LPS 30天会引发炎症细胞因子的风暴。LPS注射在体内也刺激了造血干细胞中Id1基因的转录，但在体外没有，提示间接作用。为了确定LPS处理对HSC功能的影响并评估Id1表达的意义，我们评估了野生型和Id1缺陷小鼠的繁殖潜力，这些小鼠接受30天的LPS处理方案。我们发现LPS导致野生型HSC的长期而非短期的繁殖活性显著降低，而Id1缺陷型HSC则没有。这种处理还导致野生型而非Id1缺陷小鼠的HSC计数增加，brdu标签保留减少和Ki67染色检测到的静止紊乱。综上所述，Id1至少在一定程度上在lps诱导的HSC完整性损伤中起作用。
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.
登录
查看更多内容
E2A蛋白促进淋巴酸化的多能祖细胞的发展。
影响因子：
32.4
作者：
Dias, Sheila;Mansson, Robert;Gurbuxani, Sandeep;Sigvardsson, Mikael;Kee, Barbara L.
通讯作者：
Kee, Barbara L.
DOI：
10.1126/science.1180794
发表时间：
2010-01-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li L;Clevers H
通讯作者：
Clevers H
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
64.5
作者：
BENEZRA, R;DAVIS, RL;WEINTRAUB, H
通讯作者：
WEINTRAUB, H
DOI：
10.1084/jem.194.7.941
发表时间：
2001-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bryder D;Ramsfjell V;Dybedal I;Theilgaard-Mönch K;Högerkorp CM;Adolfsson J;Borge OJ;Jacobsen SE
通讯作者：
Jacobsen SE