Proteomic analysis of integrin-associated complexes from mesenchymal stem cells.
Proteomic analysis of integrin-associated complexes from mesenchymal stem cells.
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DOI：
10.1002/prca.201500033
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Humphries JD
中科院分区：
文献类型：
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作者：
Ajeian JN;Horton ER;Astudillo P;Byron A;Askari JA;Millon-Frémillon A;Knight D;Kimber SJ;Humphries MJ;Humphries JD
多能间充质干细胞 (MSC) 具有分化脂肪细胞、骨细胞和软骨细胞谱系的能力，因此提供了一系列潜在的治疗应用。细胞周围的细胞外基质（ECM）环境的组成和硬度决定了它们的转录程序，从而影响干细胞谱系决策。细胞通过自身与其微环境之间的联系来感知力，这是通过整合素受体和相关的粘附信号复合物传递的。为了确定 MSC 力传感的调节因子，我们试图对 MSC 整合素相关的粘附复合物成分进行分类。通过 MS 分离并表征由铺在 ECM 配体纤连蛋白上的 MSC 形成的粘附复合物。通过与基于文献的细胞粘附相关成分的参考集进行比较并使用本体论和蛋白质-蛋白质相互作用网络分析来询问已识别的蛋白质。 MSC 中的粘附复合物特异性蛋白主要由细胞粘附相关接头和肌动蛋白细胞骨架调节因子组成。此外，MSC 粘附复合物中含有 LIM 结构域的蛋白质也被强调，它们可能充当力传感组件。这些数据提供了有关间充质干细胞中整合素和粘附信号传导分子连接的宝贵信息资源，因此可能为治疗干预提供新的机会。
Multipotent mesenchymal stem cells (MSCs) have the capability to differentiate down adipocyte, osteocyte and chondrocyte lineages and as such offer a range of potential therapeutic applications. The composition and stiffness of the extracellular matrix (ECM) environment that surrounds cells dictates their transcriptional programme, thereby affecting stem cell lineage decision‐making. Cells sense force via linkages between themselves and their microenvironment, and this is transmitted by integrin receptors and associated adhesion signalling complexes. To identify regulators of MSC force sensing, we sought to catalogue MSC integrin‐associated adhesion complex composition. Adhesion complexes formed by MSCs plated on the ECM ligand fibronectin were isolated and characterised by MS. Identified proteins were interrogated by comparison to a literature‐based reference set of cell adhesion‐related components and using ontological and protein–protein interaction network analyses. Adhesion complex‐specific proteins in MSCs were identified that comprised predominantly cell adhesion‐related adaptors and actin cytoskeleton regulators. Furthermore, LIM domain‐containing proteins in MSC adhesion complexes were highlighted, which may act as force‐sensing components. These data provide a valuable resource of information regarding the molecular connections that link integrins and adhesion signalling in MSCs, and as such may present novel opportunities for therapeutic intervention.