Lineage-specific exosomes could override extracellular matrix mediated human mesenchymal stem cell differentiation.
Lineage-specific exosomes could override extracellular matrix mediated human mesenchymal stem cell differentiation.
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DOI：
10.1016/j.biomaterials.2018.08.027
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发表时间：
2018-11
期刊：
影响因子：
14
通讯作者：
Rajendran VM
中科院分区：
文献类型：
--
作者：
Narayanan K;Kumar S;Padmanabhan P;Gulyas B;Wan ACA;Rajendran VM
谱系特化是干细胞命运、组织稳态和发育的重要过程。微环境信号提供直接和选择性的外在信号来调节干细胞的谱系特化。微环境由两种基本成分组成，一种是作为基质的细胞外基质（ECM），另一种是细胞分泌的外泌体和生长因子。分化细胞的ECM调节干细胞的表型表达，而它们的外泌体含有控制干细胞分化的表型特异性指导因子（miRNA、RNA和蛋白质）。这项研究表明，成骨细胞来源的（Os-Exo）和脂肪细胞来源的（Ad-Exo）外泌体含有指导性因子，调节人间充质干细胞（hMSCs）的谱系特化。外泌体分析显示，成骨细胞（RUNX 2和OSX）和脂肪细胞（C/EBPα和PPARγ）存在RNA和蛋白质形式的转录因子。此外，在这些外来体中还鉴定了几种据报道具有成骨和成脂分化潜能的miRNA。动力学和分化分析表明，成骨细胞和脂肪细胞外泌体都增强ECM介导的hMSC分化为各自的谱系。与单独施用的相应ECM或外来体相比，成骨细胞/脂肪细胞ECM和外来体的组合在更早的分化时间点开启谱系特异性基因表达。有趣的是，在具有成脂外泌体的成骨细胞ECM上分化的hMSC显示成脂谱系基因的表达，而在具有成骨外泌体的脂肪细胞ECM上分化的hMSC显示成骨谱系基因。基于这些观察结果，我们得出结论，外泌体可能会覆盖ECM介导的指导信号在hMSC的谱系特化。
Lineage specification is an essential process in stem cell fate, tissue homeostasis and development. Microenvironmental cues provide direct and selective extrinsic signals to regulate lineage specification of stem cells. Microenvironmental milieu consists of two essential components, one being extracellular matrix (ECM) as the substratum, while the other being cell secreted exosomes and growth factors. ECM of differentiated cells modulates phenotypic expression of stem cells, while their exosomes contain phenotype specific instructive factors (miRNA, RNA and proteins) that control stem cell differentiation. This study demonstrates that osteoblasts-derived (Os-Exo) and adipocytes-derived (Ad-Exo) exosomes contain instructive factors that regulate the lineage specification of human mesenchymal stem cells (hMSCs). Analyses of exosomes revealed the presence of transcription factors in the form of RNA and protein for osteoblasts (RUNX2 and OSX) and adipocytes (C/EBPα and PPARγ). In addition, several miRNAs reported to have osteogenic and adipogenic differentiation potentials are also identified in these exosomes. Kinetic and differentiation analyses indicate that both osteoblast and adipocyte exosomes augment ECM-mediated differentiation of hMSCs into the respective lineage. The combination of osteoblast/adipocyte ECM and exosomes turned-on the lineage specific gene expressions at earlier time points of differentiation compared to the respective ECM or exosomes administered individually. Interestingly, the hMSCs differentiated on osteoblast ECM with adipogenic exosomes showed expression of adipogenic lineage genes, while hMSCs differentiated on adipocyte ECM with osteoblast exosomes showed osteogenic lineage genes. Based on these observations, we conclude that exosomes might override the ECM mediated instructive signals during lineage specification of hMSC.
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DOI：
10.1038/nrm3112
发表时间：
2011-05
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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影响因子：
4.1
作者：
Huleihel, Luai;Bartolacci, Joseph G.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
4
作者：
Huang, Shan;Wang, Shihua;Zhao, Robert Chunhua
通讯作者：
Zhao, Robert Chunhua
影响因子：
16.6
作者：
Lai, Charles P.;Kim, Edward Y.;Badr, Christian E.;Weissleder, Ralph;Mempel, Thorsten R.;Tannous, Bakhos A.;Breakefield, Xandra O.
通讯作者：
Breakefield, Xandra O.
DOI：
10.1126/science.1176009
发表时间：
2009-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hynes RO
通讯作者：
Hynes RO