TAK1 (MAP3K7) signaling regulates hematopoietic stem cells through TNF-dependent and -independent mechanisms.
TAK1 (MAP3K7) signaling regulates hematopoietic stem cells through TNF-dependent and -independent mechanisms.
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TAK1 (MAP3K7) 信号通过 TNF 依赖性和非依赖性机制调节造血干细胞。
DOI：
10.1371/journal.pone.0051073
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ninomiya-Tsuji J
中科院分区：
文献类型：
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作者：
Takaesu G;Inagaki M;Takubo K;Mishina Y;Hess PR;Dean GA;Yoshimura A;Matsumoto K;Suda T;Ninomiya-Tsuji J
已知细胞因子/应激信号传导激酶Tak 1（Map 3 k7）缺陷会损害造血祖细胞。然而，TAK 1信号传导在造血系统干细胞功能中的作用尚未明确。在这里，我们的特点是造血干细胞（HSC）窝藏删除Tak 1及其激活剂，Tak 1结合蛋白1和2（Tab 1和Tab 2）在小鼠模型中使用竞争性移植试验。Tak 1单缺失或Tab 1/Tab 2双缺失可完全消除HSC的重建活性，而Tab 1或Tab 2单缺失未引起任何异常。Tak 1单或Tab 1/Tab 2双缺陷谱系阴性、Sca-1+、c-Kit+（LSK）细胞不增殖并经历细胞死亡。我们发现，Tnfr 1缺陷恢复Tak 1缺陷骨髓细胞的重建活性6-18周。然而，Tak 1和Tnfr 1双缺陷骨髓细胞的重建活性在长期内下降，表型鉴定的长期造血干细胞的数量减少。我们的研究结果表明，TAB 1或TAB 2依赖性激活TAK 1是通过两种机制维持造血系统所必需的：一种是预防TNF依赖性细胞死亡，另一种是长期HSC的TNF非依赖性维持。
A cytokine/stress signaling kinase Tak1 (Map3k7) deficiency is known to impair hematopoietic progenitor cells. However, the role of TAK1 signaling in the stem cell function of the hematopoietic system is not yet well defined. Here we characterized hematopoietic stem cells (HSCs) harboring deletion of Tak1 and its activators, Tak1 binding proteins 1 and 2 (Tab1 and Tab2) using a competitive transplantation assay in a mouse model. Tak1 single or Tab1/Tab2 double deletions completely eliminated the reconstitution activity of HSCs, whereas Tab1 or Tab2 single deletion did not cause any abnormality. Tak1 single or Tab1/Tab2 double deficient lineage-negative, Sca-1+, c-Kit+ (LSK) cells did not proliferate and underwent cell death. We found that Tnfr1 deficiency restored the reconstitution activity of Tak1 deficient bone marrow cells for 6–18 weeks. However, the reconstitution activity of Tak1- and Tnfr1-double deficient bone marrow cells declined over the long term, and the number of phenotypically identified long-term hematopoietic stem cells were diminished. Our results indicate that TAB1- or TAB2-dependent activation of TAK1 is required for maintenance of the hematopoietic system through two mechanisms: one is prevention of TNF-dependent cell death and the other is TNF-independent maintenance of long-term HSC.
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DOI：
10.4049/jimmunol.0903587
发表时间：
2010-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kajino-Sakamoto R;Omori E;Nighot PK;Blikslager AT;Matsumoto K;Ninomiya-Tsuji J
通讯作者：
Ninomiya-Tsuji J
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
30.5
作者：
Sato, S;Sanjo, H;Akira, S
通讯作者：
Akira, S
影响因子：
64.8
作者：
通讯作者：
--
肠细胞衍生的 TAK1 信号传导可防止上皮细胞凋亡以及回肠炎和结肠炎的发展。
DOI：
10.4049/jimmunol.181.2.1143
发表时间：
2008-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kajino-Sakamoto R;Inagaki M;Lippert E;Akira S;Robine S;Matsumoto K;Jobin C;Ninomiya-Tsuji J
通讯作者：
Ninomiya-Tsuji J