Abstract 3224: MicroRNA Profiling of Cardiac and Bone Marrow Stromal Cells With Identical Genetic Background Reveals Distinctive Signatures Unmodulated by Differentiation Stimuli
INTRODUCTION: Aim of the present work has been to investigate the role of miRNAs in cardiac (CSC) and bone marrow stromal cells (BMSC) with identical genetic background.
METHODS & RESULTS: MiRNA expression profiling was performed on CSC and BMSC both isolated from the same donors (n=4) and cultured in standard amplifying conditions. The results were obtained by qRT-PCR and analyzed using the comparative Ct method. Has-miR 17–5p was used as normalization reference. A specific CSC miRNA signature was identified consisting of miRNAs 126, 146a and 204 and miRNAs 10a, 10b, 196a, 196b, 221 and 615 which were respectively up- and down-regulated compared to BMSC. Next, we analysed the mirna profile of CSC and BMSC exposed to differentiation stimuli. The following points summarize our results:
vasculogenic stimulation modestly modulated miRNA expression without overlapping clouds between the two populations.
in osteogenic and adipogenic conditions a higher number of miRNAs was regulated in CSC than BMSC. Of note, miRNAs known to be involved in the adipogenic (i.e. mir-143, -107) and in the osteogenic process (i.e. mir-135a, -135b) were up-regulated in CSC, but not in BMSC, although in BMSC the adipogenic/osteogenic phenotype was more intesily expressed than in CSC.
When stimulated with a combination of All-Trans Retinoic Acid and phenylbutyrate aimed at stimulate a cardiac-like differentiation, both CSC and BMSC significantly up-regulated myo-miRNAs like mir-1, -133a, -133b and 27a. However, in this condition BMSC expressed pluripotency-associated miRNAs such as miR-302c, -302d and 200a possibly explaining their reduced cardiogenic output.
a larger number of miRNAs were also modulated in both cell population during differentiation although with unknown functions or related to other differentiation pathways not yet associated to mesenchymal cells.
Further analyses are required to elucidate this important aspect.
CONCLUSIONS: In this work we demonstrated that CSC and BMSC are distinguishable by a miRNA signatures not responsive to differentiation stimuli. A high number other miRNAs with unknown function, however, appeared commonly regulated in both cell populations.