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不同来源的人骨髓间充质干细胞的差异 microRNA 特征揭示了骨髓干细胞的“环境-生态位记忆”。

Differential microRNA signature of human mesenchymal stem cells from different sources reveals an "environmental-niche memory" for bone marrow stem cells.

机构信息

Cell Factory Franco Calori, Center of Transfusion Medicine, Cellular Therapy and Cryobiology, Department of Regenerative Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy.

出版信息

Exp Cell Res. 2013 Jun 10;319(10):1562-74. doi: 10.1016/j.yexcr.2013.04.002. Epub 2013 Apr 8.

Abstract

Human mesenchymal stem cells (MSCs) are multipotent cells offering valuable hopes for the treatment of degenerative diseases. MSCs can be found among differentiated cells in many tissues and organs but, unfortunately, their phenotypic similarity hinders a robust cell characterization and discrimination from diverse tissue harvests. MicroRNAs (miRNAs) are crucial managers of gene expression with intriguing and still poorly known roles in stem cell maintenance and differentiation. To identify miRNAs that can discriminate among MSCs, we performed a whole-genome comparative miRNA expression profiling analysis on adipose (AD), bone marrow (BM) and cord blood (CB) derived MSCs, all three considered among the most promising in the field of regenerative medicine. miRNA expression patterns were very similar, meeting their extensive phenotypic and functional overlaps. An in-depth comparison of the few most differentially expressed miRNAs allowed the identification of a highly restricted molecular signature consisting of 5 BMMSC, 11 ADMSC and 11 CBMSC specific miRNAs. Functional analysis of their validated targets allowed the identification of an "environmental-niche memory" for BMMSC and an "epithelial" commitment for ADMSC, providing new insights into the molecular mechanisms discriminating between these MSCs, a crucial element to identify the most appropriate stem cell source for clinical application.

摘要

人类间充质干细胞(MSCs)是多能细胞,为退行性疾病的治疗提供了有价值的希望。MSCs 可在许多组织和器官的分化细胞中找到,但不幸的是,其表型相似性阻碍了对其进行稳健的细胞特征分析,并使其难以从不同组织中分离。microRNAs(miRNAs)是基因表达的重要调控因子,在干细胞维持和分化中具有令人着迷且知之甚少的作用。为了鉴定能够区分 MSCs 的 miRNAs,我们对来自脂肪(AD)、骨髓(BM)和脐血(CB)的 MSCs 进行了全基因组比较 miRNA 表达谱分析,所有这三种细胞都被认为是再生医学领域最有前途的细胞之一。miRNA 表达模式非常相似,符合其广泛的表型和功能重叠。对少数差异表达最多的 miRNAs 进行深入比较,确定了一个高度受限的分子特征,包括 5 个 BMMSC、11 个 ADMSC 和 11 个 CBMSC 特异性 miRNAs。对其验证靶标的功能分析允许鉴定出 BMMSC 的“环境生态位记忆”和 ADMSC 的“上皮”决定,为区分这些 MSC 的分子机制提供了新的见解,这是确定最适合临床应用的干细胞来源的关键要素。

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