Differential expression of microRNAs at the last stage of hepatic differentiation of mesenchymal stem cells

Background and Aim: MicroRNAs (miRNAs) are small noncoding RNAs that can play essential roles in a wide variety of biological processes from proliferation and differentiation to metabolism and apoptosis. Hepatic differentiation of Mesenchymal Stem Cells (MSCs) is a highly regulated multistep process involving posttranscriptional regulation by microRNAs. In the present study, miRNA expression profiles were determined during hepatocyte-specific differentiation of Adipose Derived Mesenchymal Stem Cells (ADSCs).Methods: In this study, hADSCs were differentiated to hepatocytes by a two-step protocol for ۲۱ days and after characterization of hepatic differentiation of hADSCs by biochemical, morphological and molecular methods, a high throughput array platform (Affymetrix) was used for miRNA profiling at two time points (days ۱۴ and ۲۱).Results: By performing genome-wide miRNA profiling assay, we have identified a signature of ۳۵۴ differentially expressed canonical miRNAs (۱۶۶ upregulated; ۱۸۸ downregulated) during the last stage of hepatic differentiation of ADSCs. Top ۵ ranking miRNAs in volume with significant cut-off, ǀFCǀ≥۲ or ǀFCǀ≤۲, were hsa-miR-۴۴۹۷, hsa-miR-۴۴۵۴, hsa-miR-۲۶a-۵p, hsa-miR-۳۱۷۸, hsa-miR-۲۲۲-۳p.Conclusion: Our findings provide novel molecular insights into the identification of miRNAs regulating hepatic differentiation of ADSCs during the late stages and a roadmap for further understanding MSC biology.