Comprehensive transcriptomic and proteomic characterization of human mesenchymal stem cells reveals source specific cellular markers.

Comprehensive transcriptomic and proteomic characterization of human mesenchymal stem cells reveals source specific cellular markers.
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DOI:
10.1038/srep21507
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发表时间:
2016-02-09
期刊:
影响因子:
4.6
通讯作者:
Graumann J
Graumann J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Billing AM;Ben Hamidane H;Dib SS;Cotton RJ;Bhagwat AM;Kumar P;Hayat S;Yousri NA;Goswami N;Suhre K;Rafii A;Graumann J

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间充质干细胞(MSC)是一种多能细胞,在治疗方面具有巨大潜力,在NIH注册的500多项基于MSC的临床试验反映了这一点。MSC来源于多种组织,但需要侵入性收获,并意味着供体间的变异性。胚胎干细胞衍生的MSC(ESC-MSC)可能提供一种替代方案,但它们与离体MSC的相似程度尚不清楚。在这里,我们对人ESC-MSC进行了深入表征,通过转录组学(RNA-seq)和定量蛋白质组学(使用SILAC的nanoLC-MS/MS)将其与人骨髓来源的MSC(BM-MSC)以及人胚胎干细胞(hESC)进行了比较。数据整合强调并验证了囊泡介导的转运和外泌体在MSC生物学中的核心作用,并通过富集分析证明了它们的多功能性和广泛的应用潜力。特别强调的是比较ESC-MSC和BM-MSC之间的配置文件,并评估其等效性。这里提供的数据表明,ESC-MSC和BM-MSC之间的差异与不同来源的MSC报道的差异相似,因此前者可能代表治疗应用的替代来源。最后,我们报告了一个前所未有的覆盖范围MSC CD标记,以及膜相关蛋白,这可能有利于免疫荧光为基础的应用程序,并有助于MSC的精细分子描述。
Mesenchymal stem cells (MSC) are multipotent cells with great potential in therapy, reflected by more than 500 MSC-based clinical trials registered with the NIH. MSC are derived from multiple tissues but require invasive harvesting and imply donor-to-donor variability. Embryonic stem cell-derived MSC (ESC-MSC) may provide an alternative, but how similar they are to ex vivo MSC is unknown. Here we performed an in depth characterization of human ESC-MSC, comparing them to human bone marrow-derived MSC (BM-MSC) as well as human embryonic stem cells (hESC) by transcriptomics (RNA-seq) and quantitative proteomics (nanoLC-MS/MS using SILAC). Data integration highlighted and validated a central role of vesicle-mediated transport and exosomes in MSC biology and also demonstrated, through enrichment analysis, their versatility and broad application potential. Particular emphasis was placed on comparing profiles between ESC-MSC and BM-MSC and assessing their equivalency. Data presented here shows that differences between ESC-MSC and BM-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications. Finally, we report an unprecedented coverage of MSC CD markers, as well as membrane associated proteins which may benefit immunofluorescence-based applications and contribute to a refined molecular description of MSC.