MicroRNAs for fine-tuning of mouse Embryonic Stem Cell fate decision through regulation of TGF-β signaling. Mus musculus

Over the past years, microRNAs (miRNAs) have emerged as crucial factors that regulate self-renewal and differentiation of embryonic stem cells (ESCs). Although much is known about their role in maintaining ESC pluripotency, the mechanisms by which they affect cell fate decisions remain poorly understood. By performing deep sequencing to profile miRNAs expression in mouse ESCs (mESCs) and differentiated embryoid bodies (EBs), we identified four differentially expressed miRNAs. Among them, miR-191 and miR-16-1 are highly expressed in ESCs and repress Smad2, the most essential mediator of Activin-Nodal signaling, resulting in the inhibition of mesendoderm formation. miR-23a, which is also downregulated in the differentiated state, suppresses differentiation towards the endoderm and ectoderm lineages. We further identified miR-421 as a differentiation-associated regulator through the direct repression of core pluripotency transcription factor Oct4 and BMP-signaling components, Smad5 and Id2. Collectively, our findings uncover a regulatory network between the studied miRNAs and both branches of TGF-β/BMP signaling pathways revealing their importance for ESC lineage decisions. Overall design: miRNA profiles of ESCs and differentiated EBs D8 were generated by deep sequencing, in duplicate, using ION TORRENT PGM platform