Megakaryocytes are essential for HSC quiescence through the production of thrombopoietin
Megakaryocytes are essential for HSC quiescence through the production of thrombopoietin
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DOI：
10.1016/j.bbrc.2014.10.095
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发表时间：
2014-11-14
影响因子：
3.1
通讯作者：
Suda, Toshio
中科院分区：
文献类型：
--
作者：
Nakamura-Ishizu, Ayako;Takubo, Keiyo;Suda, Toshio
组织稳态需要调节反馈，这表明造血干细胞(HSC)的活性在一定程度上受HSC后代的控制。然而，细胞的外源性HSC调节仅在非造血源的利基细胞中得到了很好的表征。在这里，我们确定了巨核细胞(MKS)通过产生血小板生成素(THPO)对HSC的反馈调节，THPO是一种与HSC维持相关的细胞因子。对小鼠骨髓中静止的HSCs进行诱导消融。消融MKS导致BM内Thpo浓度降低，可能是由于MKS产生Thpo所致。Tpo给予Mk消融小鼠肝星状细胞功能恢复。总体而言，我们的研究确立了MK是HSC生态位的重要细胞成分，并描绘了HSC自身后代对HSC的细胞因子导向调控。(C)2014年提交人。由Elsevier Inc.出版。这是一篇CC BY-NC-ND许可下的开放获取文章。
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. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.