Differential microRNA signature of human mesenchymal stem cells from different sources reveals an “environmental-niche memory” for bone marrow stem cells

• Comparison of microRNA expression profiles in human mesenchymal stem cells.
• MicroRNA expression pattern similarity regardless of the source of stem cell isolation.
• Enriched haematopoietic functions for micoRNA gene targets in bone marrow derived stem cells.
• Enriched epithelial functions for microRNA target genes in adipose-derived stem cells.
• Novel possibilities for identification of the most appropriate stem cell source in regenerative medicine.

Human mesenchymal stem cells (MSCs) are multipotent cells offering valuable hopes for the treatment of degenerative diseases. MSCs can be found among differentiated cells in many tissues and organs but, unfortunately, their phenotypic similarity hinders a robust cell characterization and discrimination from diverse tissue harvests. MicroRNAs (miRNAs) are crucial managers of gene expression with intriguing and still poorly known roles in stem cell maintenance and differentiation. To identify miRNAs that can discriminate among MSCs, we performed a whole-genome comparative miRNA expression profiling analysis on adipose (AD), bone marrow (BM) and cord blood (CB) derived MSCs, all three considered among the most promising in the field of regenerative medicine. miRNA expression patterns were very similar, meeting their extensive phenotypic and functional overlaps. An in-depth comparison of the few most differentially expressed miRNAs allowed the identification of a highly restricted molecular signature consisting of 5 BMMSC, 11 ADMSC and 11 CBMSC specific miRNAs. Functional analysis of their validated targets allowed the identification of an “environmental-niche memory” for BMMSC and an “epithelial” commitment for ADMSC, providing new insights into the molecular mechanisms discriminating between these MSCs, a crucial element to identify the most appropriate stem cell source for clinical application.