Unfolding the non-coding RNA landscape in pluripotency and differentiation

Human Pluripotent Stem Cells (PSCs) are characterized by their self-renewal capacity and their ability to differentiate into every cell type in the body. Deciphering the molecular factors that are involved in stem cell fate decision is crucial to understanding human development. Transcription Factors (TFs) are known to play key roles in maintaining the stem cell state and in differentiation to each of the three germ line layers. In recent years, long intergenic non-coding RNAs (lincRNAs) have emerged as regulators of pluripotency and differentiation. To study the role of lincRNAs in stem cell fate, we generated RNA-seq data from eleven time points during directed differentiation to cardiomyocytes. We clustered the lincRNAs with known markers of pluripotency and differentiation which revealed over 500 differentially expressed non-coding RNAs, putatively involved in different steps of cardiac differentiation. Furthermore, we explored the expression of alternatively spliced isoforms of TFs and lincRNAs throughout the experiment. We discovered dozens of TFs and lincRNA genes, which their alternative transcript shows a distinct pattern of expression during pluripotency and differentiation, suggesting an important role for alternative RNA processing of coding and non-coding RNAs in early human development.