Differential expression of circRNA in adult and fetal mesenchymal stem cells and fibroblasts

Stem cell identity is typically controlled by master regulatory genes and by complex circuits of a growing family of noncoding RNA (ncRNA) molecules, which impact cell phenotype maintenance and plasticity. Yet, these self-reinforcing regulatory networks are still poorly defined for human primary mesenchymal stem cells (MSCs), in particular with respect to ncRNA. Circular RNAs (circRNAs) are a new class of RNAs commonly generated from protein-coding genes by back-splicing events, resulting in a highly stable RNA structure, devoid of free 5’ and 3’ ends. Even though circRNAs are expressed across eukaryotes and may regulate gene expression, their precise mechanisms of action in stem cell biology have remained unexplored until now. In this study, for the first time, we determined that a circRNA has a role in the control of MSC fate and undifferentiated identity. Our starting point was high-throughput expression profiling of MSCs from different sources, which revealed a large number of differentially expressed circRNAs. n=3 donors for each cell population. A preliminary analysis was performed on n=1 donor for each cell population (BMMSC_1, CBMSC_1, HSF_1). A second separate expression profile was obtained on n=2 donors for each cell population (remaining samples). A ComBat correction was applied to take into account batch effect (see raw and normalized data).