Nakamura-Ishizu Ayako, Takubo Keiyo, Fujioka Masato, Suda Toshio
Biochem Biophys Res Commun. 2014 Nov 14;454(2):353-7. doi: 10.1016/j.bbrc.2014.10.095. Epub 2014 Oct 24.
Tissue homeostasis demands regulatory feedback, suggesting that hematopoietic stem cell (HSC) activity is controlled in part by HSC progeny. Yet, cell extrinsic HSC regulation has been well characterized only in niche cells of non-hematopoietic origin. Here we identify feedback regulation of HSCs by megakaryocytes (Mks), which are mature hematopoietic cells, through production of thrombopoietin (Thpo), a cytokine pertinent for HSC maintenance. Induced ablation of Mk cell population in mice perturbed quiescent HSCs in bone marrow (BM). The ablation of Mks resulted in decreased intra-BM Thpo concentration presumably due to Thpo production by Mks. Thpo administration Mk ablated mice restored HSC functions. Overall, our study establishes Mk as an essential cellular component of the HSC niche and delineates cytokine-oriented regulation of HSCs by their own progeny.
组织稳态需要调节反馈，这表明造血干细胞（HSC）的活性部分受HSC子代细胞的控制。然而，细胞外源性HSC调节仅在非造血来源的微环境细胞中得到了充分表征。在这里，我们发现巨核细胞（Mk）作为成熟的造血细胞，通过产生血小板生成素（Thpo，一种对HSC维持至关重要的细胞因子）对HSCs进行反馈调节。在小鼠中诱导性消融Mk细胞群会扰乱骨髓（BM）中静止的HSCs。Mks的消融导致BM内Thpo浓度降低，这可能是由于Mks产生Thpo所致。给Mk消融的小鼠注射Thpo可恢复HSC功能。总体而言，我们的研究确立了Mk作为HSC微环境的重要细胞组成部分，并阐明了HSCs子代细胞通过细胞因子对其进行的调节。
