Transcriptomic characterization of human Mesenchymal Stromal/Stem Cells

Abstract

The therapeutically applied population of Mesenchymal Stromal/Stem Cells, defined under the minimal criteria of the International Society of Cellular Therapy (ISCT), have still a defectively characterized phenotype difficult to distinguish from similar cell populations. This Doctoral Thesis has been formulated as a characterizing data-driven approach. Thus, the main scope is to improve the characterization of the phenotype of human mesenchymal stem/stromal cells. We have approached such scope through a deep comparative transcriptomic study applying high-throughput genome-wide analytic techniques: producing and integrating RNA sequencing and microarray data assays, with a meta-analysis of a large collection of public expression data. The research falls within the fields of cellular, molecular and systems biology, which entails two complementary approaches: the experimental, and the computational ones. First, we isolated, cultured and validated (following the ISCT criteria of immunophenotype and in-vitro tri-lineage differentiation) human MSCs from three tissue origins: placenta, bone marrow, and adipose tissue. Applying bioinformatics techniques, we then defined a gene expression signature common to all human tissue-MSCs, as well as the specific expression profiles associated to each tissue-MSC type. Based on these achievements, we could come up with novel insights about the MSC phenotype that will lead to the drafting of new hypotheses. Also, we yielded a broad transcriptomic signature resource ready to serve as reference on upcoming identification studies.