Molecular characterization of heterogeneous mesenchymal stem cells with single-cell transcriptomes.

Molecular characterization of heterogeneous mesenchymal stem cells with single-cell transcriptomes.
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DOI:
10.1016/j.biotechadv.2012.12.003
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发表时间:
2013-03
影响因子:
16
通讯作者:
Zhong, Jiang F.
Zhong, Jiang F.
中科院分区:
工程技术1区
文献类型:
--
作者:
Li, Zhongjun;Zhang, Chao;Weiner, Leslie P.;Zhang, Yiqiang;Zhong, Jiang F.

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间充质干细胞(MSC)是一种异质细胞群,在再生医学领域具有潜在的治疗潜力。骨髓间充质干细胞在不同临床情况下的治疗价值已有报道。克隆分析(MSC从单个细胞扩增)表明,在MSC群体中存在多种具有不同发育潜力的细胞。由于MSC的异质性,在缺乏已知生物标志物的情况下,MSC的分子特征是MSC细胞治疗的一个挑战。在这里,我们回顾了MSC潜在的治疗应用,并讨论了一种利用单细胞转录组分析对不同细胞群体进行分子表征的系统方法。细胞的分化/成熟是通过一系列基因在细胞内的顺序表达来调控的。因此,来自连续发育阶段的单细胞mRNA表达(转录组)图谱比来自不同阶段的更相似。生物信息学分析可以将连续发育阶段的单细胞转录组图谱聚类成基于这些图谱的相似性矩阵的树状图。由于单个细胞在表达谱中是一个最终的“纯”样本,这些树状图可用于在没有已知生物标志物的不同细胞群体中将单个细胞分类为分子亚群。这种方法在研究分子信息和已知生物标记物很少的细胞群体时尤其有效,例如MSC群体。这种分子理解将为利用小分子和其他药物操纵MSC分化提供新的靶点,使MSC能够更安全、更有效地应用于治疗。
Mesenchymal stem cells (MSC) are heterogeneous cell populations with promising therapeutic potentials in regenerative medicine. The therapeutic values of MSC in various clinical situations have been reported. Clonal assays (expansion of MSC from a single cell) demonstrated that multiple types of cells with different developmental potential exist in a MSC population. Due to the heterogeneous nature of MSC, molecular characterization of MSC in the absence of known biomarkers is a challenge for cell therapy with MSC. Here, we review potential therapeutic applications of MSC and discuss a systematic approach for molecular characterization of heterogeneous cell population using single-cell transcriptome analysis. Differentiation/maturation of cells is orchestrated by sequential expression of a series of genes within a cell. Therefore, single-cell mRNA expression (transcriptome) profiles from consecutive developmental stages are more similar than those from disparate stages. Bioinformatic analysis can cluster single-cell transcriptome profiles from consecutive developmental stages into a dendrogram based on the similarity matrix of these profiles. Because a single-cell is an ultimately “pure” sample in expression profiling, these dendrograms can be used to classify individual cells into molecular subpopulations within a heterogeneous cell population without known biomarkers. This approach is especially powerful in studying cell populations with little molecular information and few known biomarkers, for example the MSC populations. The molecular understanding will provide novel targets for manipulating MSC differentiation with small molecules and other drugs to enable safer and more effective therapeutic applications of MSC.
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影响因子: --
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发表时间: 2012-01-26
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