| PMC full text: | Nat Rev Mol Cell Biol. Author manuscript; available in PMC 2014 Aug 1. Published in final edited form as: Nat Rev Mol Cell Biol. 2009 Feb; 10(2): 116–125. doi: 10.1038/nrm2621 |
Figure 1
Embryonic stem (ES) cells have the ability to self-renew or differentiate into progenitor cells, which finally give rise to all of the adult tissue stem cells in the body. MicroRNAs (miRNAs) regulate both self-renewal and differentiation pathways of ES cells by regulating various factors that mediate these processes. miRNAs form an integral network with transcription factors in regulating stem cell processes. For example, RE1-silencing transcription factor (REST), a transcriptional repressor, downregulates miR-21, which targets Nanog, SOX2 and OCT4 (also known as OCT3 and POU5F1). These are essential for stem cell self-renewal. Therefore, REST promotes self-renewal26. Self-renewal is also promoted by the miR-290–295 cluster, which targets retinoblastoma like 2 (RBL2) — a repressor of DNA methyl transferases (DNMTs) — which methylate CpG islands and epigenetically silence OCT4 (REFS 29,30). Another mechanism of promoting self-renewal is by the regulation of let-7 miRNA processing by LIN28, which directly binds to a consensus sequence in the pre-let-7 miRNA loop region and inhibits processing by Drosha and Dicer32,33. miR-296 promotes ES cell differentiation and miR-22 inhibits ES cell differentiation. However, their mRNA targets have not been identified. Positive and negative regulations are shown by an arrow and a T line respectively; a dotted T line suggests a possible pathway that needs to be confirmed.
