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.
['Roson-Burgo|Beatriz|B|', 'Sanchez-Guijo|Fermin|F|', 'Del Cañizo|Consuelo|C|', 'De Las Rivas|Javier|J|']
D000273:Adipose Tissue D015415:Biomarkers D001854:Bone Marrow Cells D002454:Cell Differentiation D019070:Cell Lineage D016000:Cluster Analysis D019295:Computational Biology D005260:Female D020869:Gene Expression Profiling D018507:Gene Expression Regulation, Developmental D053263:Gene Regulatory Networks D006801:Humans D059630:Mesenchymal Stem Cells D009928:Organ Specificity D010920:Placenta D011247:Pregnancy D059467:Transcriptome
Mesenchymal stem cells Adipose tissue Placenta Bone marrow CD marker Bioinformatic meta-analysis Cytokines Human gene expression Stromal cells