IDENTIFICATION OF ISOMIRS DURING CARDIAC DIFFERENTIATION: A POTENTIALLY SIGNIFICANT AMPLIFICATION SIGNAL OF THE MIRNOMA

XIMENA GARATE; ALEJANDRO LA GRECA; GABRIEL NEIMAN; LUCIA MORO; CARLOS LUZZANI; GUSTAVO SEVLEVER; LEONARDO ROMORINI; SANTIAGO MIRIUKA

Buenos Aires

Congreso; SAIC 2017; 2017

SAIC

MicroRNAs work by fine tuning the expression of key developmental genes. Deeper analyses of microRNA expression revealed that many of them are expressed with small changes in their sequences, termed isomiRs, what possibly have a huge repercussion on the pool of mRNA targets. MicroRNAs belong to different families and clusters, when they share the seed sequence and when they are proximate in the genome, respectively. In this work, we study microRNAs and isomiRs expression changes during cardiac differentiation from pluripotent stem cells by high throughput RNA sequencing and analyze the families and clusters to establish the miRnome identity based on them.We studied pluripotent stem cells (PSC), an early mesoderm progenitor (MPC) and isolated cardiomyocytes (CM), both derived from PSC. Approximately 700 microRNAs are expressed in the three groups. Unsupervised soft clustering revealed five general patterns of microRNA differential expression. Interestingly, the isomiR analysis showed a widely disperse expression of the isoforms on the 3? extreme (iso3) (60±4.2% for PSC, 68.4±1.5% for MPC, and 61.3±5.6% for CM), but the percentage of 5? extreme (iso5) decreases significantly in the cardiac stage (7.2±0.8% for PSC, 7.8±0.7% for MPC, and 2.9±1% for CM). Moreover, we identified several iso5 significantly expressed corresponding to pluripotent-related microRNAs (i.e. mir-302 family) broadening their specificity for target mRNAs. Finally, further analysis of the microRNAs families and clusters expression profiles revealed that both groups are quite similar. PCA and SD analysis showed a slight improvement in the discrimination between populations when analyzing expression profiles of clusters.In conclusion, a wider analysis of microRNAs expression exposes an extended network of them and their respective isomiRs and analyzing families and cluster expression profiles allows to identify new insights into the miRnome identity during cardiac differentiation.