Abstract 14715: Syngeneic Cardiac and Bone Marrow Stromal Cells Display Tissue-Specific microRNA Signatures and microRNA Subsets Restricted to Diverse Differentiation Processes
BACKGROUND: Our previous findings showed that stromal cells of different origin, i.e. cardiac (CStC) and bone marrow (BMStC), have a small set of differentially expressed microRNAs (miRs). The aim of the present work was to identify (1) cell-type-specific miR signatures and (2) miR subsets exclusively modified by differentiation stimuli.
METHODS: CStC and BMStC were isolated from the same donor (n=3), cultured in standard amplification medium, and then in vitro exposed to adipogenic, osteogenic, endothelial and cardiomyogenic media. Expression profiles were assessed by RT-qPCR. Data were analyzed by 2-way ANOVA (P<0.01), followed by post-hoc pairwise comparisons (P<0.05).
RESULTS: Analysis revealed a cell-specific signature independent of culturing media and consisting of 10 miRs, 4 of which (miR-660, 501, 146a, and 532) were overexpressed, 4 (miR-10a, 196b, 199a, and 203) decreased, and 2 (miR-196a and 615) virtually absent in CStC vs. BMStC. The latter six are known to control cell cycle, proliferation and development: miR-196a and 10a are encoded in genes embedded in HOX clusters, whereas miR-199a may have a role in transcriptional regulation by targeting the SWI/SNF complex. MiR-146a and 532 are implicated in proliferation and survival; miR-146a is known to be involved in regulation of IFN and NF-κB pathways. Further, we identified miRs modulated only by differentiation stimuli independently from tissue origin. MiR-155 and 18a were down-, while miR-517c and 22 were upregulated by all differentiation stimuli. MiR-155, 18a, and 22 are known to be involved in cell cycle, and/or proliferation, survival and differentiation; miR-517 is involved in transcriptional regulation by modulating chromatin and histone modifications. In line with their known role in osteogenesis, miR-100 was down-, and miR-374 and 342 were upregulated by osteogenic medium in both cell types.
CONCLUSION: Our results demonstrated the existence of a tissue-specific miR signature, which survived to any differentiation stimuli, suggesting a role in determining cell identity related to tissue origin. Moreover, we identified miR subsets modulated by different culture conditions irrespective of tissue origin, pointing out their importance during differentiation processes.
- © 2013 by American Heart Association, Inc.