Abstract
MicroRNAs (miRNAs) regulate critical cell processes, such as apoptosis, proliferation, and development. However, the role of miRNAs in embryonic stem cell (ESC) neural differentiation induced by retinoic acid (RA) and factors that govern neural directional differentiation remain poorly understood. In this study, we demonstrated that miR-219 is sufficient in promoting mouse ESCs to undergo neural differentiation. We discovered that Foxj3 and Zbtb18, two target genes of miR-219, are not able to determine the process of RA-induced differentiation, however they prevent ESCs from differentiating into neural cells. We identified four downstream genes, namely, Olig1, Zic5, Erbb2, and Olig2, which are essential to the gene interaction networks for neural differentiation. These data explain the mechanism of RA-induced neural differentiation of mESCs on the basis of miRNAs and support the crucial role of miR-219 in neurodevelopment.
Highlights
MicroRNAs are a class of non-coding, singlestranded, and 22–25-nucleotide RNA molecules that negatively regulate gene expression in plants and animals.[1]
We determined whether or not miRNAs are involved in retinoic acid (RA)-induced neural directional differentiation by performing an array-based miRNA profiling on mouse J1 embryonic stem cells (ESCs) (gene expression omnibus (GEO) accession number: GSE54145; all tested miRNAs sorted by names are listed in Supplementary Data s03)
The results showed that 43 miRNAs were upregulated and 281 miRNAs were downregulated after 48 h of RA treatment in ESCs
Summary
MicroRNAs (miRNAs) are a class of non-coding, singlestranded, and 22–25-nucleotide RNA molecules that negatively regulate gene expression in plants and animals.[1]. All-trans retinoic acid (RA), a metabolic compound derived from Vitamin A, is important in cellular differentiation and neurogenesis.[12,13,14,15,16,17] RA is the most used morphogen for producing neural progenitor cells and neurons from pluripotent stem cells in vitro.[18,19,20,21] The action of RA on differentiation is probably mediated by RA receptors (RARs) in the nucleus This action is done through the binding of the receptors to DNA sequences located in the promoter regions of RA-responsive genes.[17,22,23] the molecular signaling pathways involved in neuronal differentiation are complex. These results provide a theoretical basis for RA application in ESC research and make a contribution to the understanding of neural regulatory networks
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
