Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis.
Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis.
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DOI：
10.1038/ncomms13500
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发表时间：
2016-12-01
影响因子：
16.6
通讯作者：
Verfaillie, Catherine M.
中科院分区：
文献类型：
--
作者：
Khurana, Satish;Schouteden, Sarah;Manesia, Javed K.;Santamaria-Martinez, Albert;Huelsken, Joerg;Lacy-Hulbert, Adam;Verfaillie, Catherine M.
整合素在骨髓生态位造血干细胞（HSC）维持中发挥重要作用。本研究表明，Periostin （Postn）通过与Integrin-αv （Itgav）相互作用调控HSC增殖。Postn的系统性缺失导致外周血（PB）贫血、骨髓单核细胞增多症和淋巴细胞减少症，而骨髓中表型hsc的数量增加。后n - / -小鼠从辐射损伤中恢复得更快，同时伴有原始hsc的丢失。来自post - / -小鼠的hsc显示DNA损伤的积累，通常与衰老的hsc相关。造血系统中的Itgav缺失导致类似的PB表型和hsc固有的再生缺陷。不受Postn影响，Vav-Itgav - / - hsc在体外增殖更快，说明了Postn- itgav相互作用的重要性。最后，Postn-Itgav相互作用抑制hsc中的FAK/PI3K/AKT通路，导致p27Kip1表达增加，从而改善静止hsc的维持。总之，我们证明了itgav介导的外向内信号在调节HSC增殖和干性中的作用。整合素调节造血干细胞（HSC）稳态和移植后植入骨髓（BM）生态位。在这里，作者表明HSC在BM中的静止和功能是由PERIOSTIN和INTEGRIN αv的相互作用以及随后p27Kip1的增加所调节的。
Integrins play an important role in haematopoietic stem cell (HSC) maintenance in the bone marrow niche. Here, we demonstrate that Periostin (Postn) via interaction with Integrin-αv (Itgav) regulates HSC proliferation. Systemic deletion of Postn results in peripheral blood (PB) anaemia, myelomonocytosis and lymphopenia, while the number of phenotypic HSCs increases in the bone marrow. Postn−/− mice recover faster from radiation injury with concomitant loss of primitive HSCs. HSCs from Postn−/− mice show accumulation of DNA damage generally associated with aged HSCs. Itgav deletion in the haematopoietic system leads to a similar PB phenotype and HSC-intrinsic repopulation defects. Unaffected by Postn, Vav-Itgav−/− HSCs proliferate faster in vitro, illustrating the importance of Postn-Itgav interaction. Finally, the Postn-Itgav interaction inhibits the FAK/PI3K/AKT pathway in HSCs, leading to increase in p27Kip1 expression resulting in improved maintenance of quiescent HSCs. Together, we demonstrate a role for Itgav-mediated outside-in signalling in regulation of HSC proliferation and stemness. Integrins regulate haematopoietic stem cell (HSC) homeostasis and engraftment into the bone marrow (BM) niche upon transplantation. Here, the authors show that HSC quiescence and function in the BM is regulated by the interaction of PERIOSTIN and INTEGRIN αv and subsequent increase in p27Kip1.
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DOI：
10.1186/cc9327
发表时间：
2010
期刊：
Critical care (London, England)
影响因子：
--
作者：
Karlsson S;Heikkinen M;Pettilä V;Alila S;Väisänen S;Pulkki K;Kolho E;Ruokonen E;Finnsepsis Study Group
通讯作者：
Finnsepsis Study Group
影响因子：
4.5
作者：
Biteau B;Karpac J;Supoyo S;Degennaro M;Lehmann R;Jasper H
通讯作者：
Jasper H
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
64.8
作者：
Hock, H;Hamblen, MJ;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
56.9
作者：
Cheng, T;Rodrigues, N;Scadden, DT
通讯作者：
Scadden, DT