microRNAs Regulating Human and Mouse Naïve Pluripotency

Abstract

microRNAs are ~22bp nucleotide non-coding RNAs that play important roles in the post-transcriptional regulation of gene expression. Many studies have established that microRNAs are important for cell fate choices, including the naïve to primed pluripotency state transitions, and their intermediate state, the developmentally suspended diapause state in early development. However, the full extent of microRNAs associated with these stage transitions in human and mouse remain under-explored. By meta-analysis of microRNA-seq, RNA-seq, and metabolomics datasets from human and mouse, we found a set of microRNAs, and importantly, their experimentally validated target genes that show consistent changes in naïve to primed transitions (microRNA up, target genes down, or vice versa). The targets of these microRNAs regulate developmental pathways (e.g., the Hedgehog-pathway), primary cilium, and remodeling of metabolic processes (oxidative phosphorylation, fatty acid metabolism, and amino acid transport) during the transition. Importantly, we identified 115 microRNAs that significantly change in the same direction in naïve to primed transitions in both human and mouse, many of which are novel candidate regulators of pluripotency. Furthermore, we identified 38 microRNAs and 274 target genes that may be involved in diapause, where embryonic development is temporarily suspended prior to implantation to uterus. The upregulated target genes suggest that microRNAs activate stress response in the diapause stage. In conclusion, we provide a comprehensive resource of microRNAs and their target genes involved in naïve to primed transition and in the paused intermediate, the embryonic diapause stage.

New directions to understand and learn from embryonic diapause in mammals

“…Specifically, microRNA target genes showed more enrichment in stress response, hypoxia, and hormone response pathways, which is consistent with the diapause phenotype. Inversely, target genes down-regulated in diapause (their microRNAs being up-regulated in diapause) showed enrichment in cellular morphogenesis, differentiation, and development, which is consistent with diapause as a suspended developmental stage [3].…”

“…More micro-RNA explorations Micro-RNAs regulate gene expression in different physiological systems. While micro-RNAs of the Let-7 family have been previously shown to be potentially regulating diapause, additional microRNA regulators of diapause and their target genes still remain to be explored [3]. Interestingly, consistent connections between 38 microRNA and 274 target genes were identified for up or down regulations in the mouse model.…”

The Key Role of MicroRNAs in Self-Renewal and Differentiation of Embryonic Stem Cells

“…MicroRNAs can be expressed in cell- and developmental-specific manners [ 110 ]. A recent meta-analysis evaluating data obtained from microRNA-seq, RNA-seq and metabolomics datasets from mouse and human ESCs revealed that 115 miRNAs show a differential expression profile during the naïve-to-primed transition [ 111 ]. These miRNAs act by repressing the developmental SONIC HEDGEHOG (SHH) pathway in the naïve state and regulating metabolic pathways such as oxidative phosphorylation, fatty acid metabolism and amino acid transport during the transition.…”

Clinical Significance of MicroRNA-155 Regulated Autophagy and Apoptosis by targeting gene Rictor/Fos in Gastric Cancer Progression

“…MicroRNAs, a class of single-stranded non-coding RNA, are widespread in various organisms, regulate gene expression at post-transcriptional level [1][2][3][4] , and also play important roles in inflammation, tumorigenesis and progression [5][6][7] . MicroRNA-155 is located on chromosome 21q21 and aberrantly expressed in a variety of solid tumors.…”