Interleukin-6 signaling regulates hematopoietic stem cell emergence
Interleukin-6 signaling regulates hematopoietic stem cell emergence
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Interleukin-6 信号传导调节造血干细胞的出现
DOI：
10.1038/s12276-019-0320-5
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发表时间：
2019-10-24
影响因子：
12.8
通讯作者：
Huang, He
中科院分区：
文献类型：
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作者：
Tie, Ruxiu;Li, Honghu;Huang, He
造血干细胞（HSC）在生物体的一生中产生所有成熟血细胞谱系。在脊椎动物中，HSC来源于胚胎背主动脉底部的生血内皮（HE）的过渡。近年来，一系列促炎因子如肿瘤坏死因子-α、干扰素-γ和Toll样受体4等被证实在HSC的特化过程中发挥关键作用。然而，到目前为止，必要的信号输入的完整补充仍然未知。在这里，我们表明，白细胞介素-6R（IL 6 R）通过IL 6是必需的，足够的HSC生成。我们发现Notch通过调节IL 6 R在HE和HSC中的表达来激活IL 6 R。IL 6的分泌主要来源于HSC非依赖性髓样细胞，而不是来自HSC及其邻近的血管内皮细胞。此外，阻断IL 6信号传导不影响血管发育或原始红细胞的产生。综上所述，我们的研究结果揭示了IL 6信号传导和HSC产生之间先前模糊的关系，并为体外使用促炎因子进行HSC再生提供了新的见解。
Hematopoietic stem cells (HSCs) produce all lineages of mature blood cells for the lifetime of an organism. In vertebrates, HSCs derive from the transition of the hemogenic endothelium (HE) in the floor of the embryonic dorsal aorta. Most recently, a series of proinflammatory factors, such as tumor necrosis factor-α, interferon-γ, and Toll-like receptor 4, have been confirmed to play a key role in HSC specification. However, the full complement of necessary signaling inputs remains unknown to date. Here, we show that interleukin-6R (IL6R) via IL6 is required and sufficient for HSC generation. We found that Notch activates IL6R by regulating its expression in the HE and in HSCs. The secretion of IL6 mainly originates from HSC-independent myeloid cells, but not from HSCs and their adjacent vascular endothelial cells. In addition, blocking IL6 signaling does not affect vascular development or the production of primitive erythrocytes. Taken together, our results uncover a previously obscure relationship between IL6 signaling and HSC production and provide new insights into HSC regeneration using proinflammatory factors in vitro.