Mesoderm and myogenesis-related lncRNAs as Potential Markers of Myogenic Differentiation of Control and miR145 or miR181 Stimulated Mouse Pluripotent Stem Cells.

Non-coding RNAs play a crucial role in the regulation of gene expression, impacting all processes occurring in a living cell. Among them are microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which interplay with each other modulating the expression of target genes. In the current study, we focused on lncRNAs described as involved in mesoderm specification or proliferation and differentiation of myogenic precursor cells and verified which of them may indeed be useful as candidate markers of mesodermal/myogenic differentiation of pluripotent stem cells (PSCs). As a model, we used two mouse embryonic stem cell (ESC) lines. We compared cells differentiating in the control medium with those induced to undergo myogenic differentiation by retinoic acid, insulin, transferrin, and selenium treatment. We showed that such induced ESC differentiation upregulated expression of few lncRNAs, i.e., yylncT, H19, SRA, and linc-YY1, in both lines. The expression of other analyzed lncRNAs changed in the ESC line specific manner. Next, we studied the impact of miR145 or miR181, which we have previously documented to elevate myogenic gene expression, on lncRNA levels. We found that miR145 overexpression resulted in decrease in H19 in both ESC types. Another common change observed in both cell lines was decrease of H19 in response to miR181. Again, the expression of most lncRNAs known as mesodermal and myogenic regulators and studied by us occurred in ESC line-dependent, and diverse manner. For the first time we verified if and which lncRNAs may serve as a potential indicators of up-and-coming myogenic differentiation. However, it should obviously be tested by extensive studies that include multiple different PSC lines.