L-Proline remodels non-coding RNA gene expression profiles in Embryonic Stem Cells

Naturally occurring amino acids are emerging as key players in the regulation of the phenotypic plasticity of stem cells. We have recently shown that a rapid increase in the extracellular availability of the nonessential amino acid L-Proline (L-Pro) forces Embryonic Stem Cells (ESCs) towards a phenotypic transition named embryonic stem cell-to-mesenchymal-like transition (esMT) that converts compact-adherent ESCs into mesenchymal-like spindle-shaped, highly motile, invasive and metastatic stem cells named L-Pro-induced cells (PiCs). Despite the relevance of such phenomenon, however, the molecular mechanisms underlying L-Pro control of ESC behavior/identity remain largely unknown. To get clues on the molecular mechanisms driving L-Pro-induced esMT, we searched for L-Pro-responsive mRNAs, miRNAs and lncRNAs by performing genome-wide expression analysis. In particular, we identified a number of miRNAs and Ultra Conserved Regions (UCRs) that are specifically and differentially expressed in PiCs with respect to ESCs. Our results reveal a unique time-dependent signature of non-coding RNAs during L-Pro-induced transition of ESCs.