Data from: Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling

Background: 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. Results: 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. Conclusions: 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.

背景：按照国际细胞治疗学会（International Society for Cellular Therapy, ISCT）制定的标准分离得到的间充质基质/干细胞（Mesenchymal Stromal/Stem Cells，MSCs），其表型仍未得到充分表征，且难以与同类细胞群区分开来。尽管转录组学和功能基因组学领域在近十年间发展迅猛，但目前尚未在具有生物学意义的细胞背景下，对人类MSCs的表达谱开展深入的比较分析。此外，当前仍亟需明确界定MSCs的基因特征，因为近期多项生物医学研究表明，关键细胞互作过程（如免疫调节、细胞串扰、细胞维持、分化及上皮-间质转化）均依赖于基质微环境中的间充质干细胞。结果：本研究通过对多组转录组表达数据集开展深入比较分析，界定了一套包含489个基因的核心间充质谱系特征，所分析的数据集涵盖：(i) 不同组织来源的MSCs；(ii) 不同分化定向状态的MSCs；(iii) 其他相关非间充质人类细胞类型。本研究整合了多份公共数据集，以及全新构建的微阵列与RNA-Seq数据集。研究结果揭示了脂肪组织、绒毛膜胎盘及骨髓来源MSCs，以及皮肤成纤维细胞的组织特异性特征，进一步明确了成纤维细胞与MSCs之间的关联。最后，本研究还解析了全新的CD标志物模式及细胞因子受体谱，尤其是针对骨髓来源MSCs（BM-MSCs），并发现MCAM（CD146）可作为该亚型MSCs的优势标志物。结论：本研究优化了人类MSCs的生物分子表征，并发布了全基因组表达特征数据集，这一全面的新型资源可为后续功能研究及重新设计的细胞治疗应用提供有力支撑。