Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling.
Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling.
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DOI：
10.1186/s12864-016-3230-0
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发表时间：
2016-11-21
期刊：
影响因子：
4.4
通讯作者：
De Las Rivas J
中科院分区：
文献类型：
--
作者：
Roson-Burgo B;Sanchez-Guijo F;Del Cañizo C;De Las Rivas J
在ISCT建立的标准下分离的间充质基质/干细胞（MSCs）仍然具有较差的表型特征，难以与相似的细胞群区分。尽管转录组学和功能基因组学领域在过去十年中迅速发展，但在有意义的细胞背景下对人类间充质干细胞表达谱的深入比较分析尚未进行。由于最近的许多生物医学研究表明，关键的细胞相互作用过程（如免疫调节、细胞串扰、细胞维持、分化、上皮-间充质转化）依赖于基质生态位内的间充质干细胞，因此还需要找到一个明确的间充质干细胞基因特征。在这项工作中，我们根据多个转录组表达数据系列的深入比较分析，定义了489个基因的核心间充质谱系特征，包括：(i)不同组织来源的间充质干细胞；（ii）处于不同承诺状态的msc；（iii）其他相关的非间充质人细胞类型。这项工作整合了几个公共数据集，以及de-novo生产的微阵列和RNA-Seq数据集。结果显示脂肪组织、绒毛膜胎盘、骨髓间充质干细胞以及真皮成纤维细胞的组织特异性特征；为成纤维细胞和间充质干细胞之间的关系提供了更好的定义。最后，揭示了新的CD标记模式和细胞因子受体谱，特别是针对BM-MSCs；MCAM （CD146）是该亚型间充质干细胞中普遍存在的标记物。改进的人间充质干细胞的生物分子特征和释放的全基因组表达特征为进一步的功能研究和重新设计细胞治疗应用提供了全面的新资源。本文的在线版本（doi:10.1186/s12864-016-3230-0）包含补充材料，授权用户可以使用。
Mesenchymal Stromal/Stem Cells (MSCs), isolated under the criteria established by the ISCT, still have a poorly characterized phenotype that is difficult to distinguish from similar cell populations. Although the field of transcriptomics and functional genomics has quickly grown in the last decade, a deep comparative analysis of human MSCs expression profiles in a meaningful cellular context has not been yet performed. There is also a need to find a well-defined MSCs gene-signature because many recent biomedical studies show that key cellular interaction processes (i.e. inmuno-modulation, cellular cross-talk, cellular maintenance, differentiation, epithelial-mesenchymal transition) are dependent on the mesenchymal stem cells within the stromal niche. In this work we define a core mesenchymal lineage signature of 489 genes based on a deep comparative analysis of multiple transcriptomic expression data series that comprise: (i) MSCs of different tissue origins; (ii) MSCs in different states of commitment; (iii) other related non-mesenchymal human cell types. The work integrates several public datasets, as well as de-novo produced microarray and RNA-Seq datasets. The results present tissue-specific signatures for adipose tissue, chorionic placenta, and bone marrow MSCs, as well as for dermal fibroblasts; providing a better definition of the relationship between fibroblasts and MSCs. Finally, novel CD marker patterns and cytokine-receptor profiles are unravelled, especially for BM-MSCs; with MCAM (CD146) revealed as a prevalent marker in this subtype of MSCs. The improved biomolecular characterization and the released genome-wide expression signatures of human MSCs provide a comprehensive new resource that can drive further functional studies and redesigned cell therapy applications. The online version of this article (doi:10.1186/s12864-016-3230-0) contains supplementary material, which is available to authorized users.
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