Abstract
Early embryonic development in mammals, from fertilization to implantation, can be viewed as a process in which stem cells alternate between self-renewal and differentiation. During this process, the fates of stem cells in embryos are gradually specified, from the totipotent state, through the segregation of embryonic and extraembryonic lineages, to the molecular and cellular defined progenitors. Most of those stem cells with different potencies in vivo can be propagated in vitro and recapitulate their differentiation abilities. Complex and coordinated regulations, such as epigenetic reprogramming, maternal RNA clearance, transcriptional and translational landscape changes, as well as the signal transduction, are required for the proper development of early embryos. Accumulated studies suggest that Dicer-dependent noncoding RNAs, including microRNAs (miRNAs) and endogenous small-interfering RNAs (endo-siRNAs), are involved in those regulations and therefore modulate biological properties of stem cells in vitro and in vivo. Elucidating roles of these noncoding RNAs will give us a more comprehensive picture of mammalian embryonic development and enable us to modulate stem cell potencies. In this review, we will discuss roles of miRNAs in regulating the maintenance and cell fate potential of stem cells in/from mouse and human early embryos.
Highlights
In mammals, early embryonic development can be divided into two stages, the pre-implantation stage and the post-implantation stage
Mammalian pri-miRNAs are methylated by methyltransferase-like 3 (Mettl3) [11] and processed into 60–70 nt precursor miRNAs by microprocessor complexes, which consist of an RNase III enzyme, Drosha, and an RNA-binding protein, DiGeorge syndrome critical region gene 8 (Dgcr8) [12]
MESCs and Human ESCs (hESCs) share similar embryonic origins, there are fundamental differences between Mouse ESCs (mESCs) and hESCs: (1) the morphology of hESC colonies is flattened, while mESC colonies are in a dome shape; (2) different pluripotency markers, such as SSEA-3 and SSEA-4, are expressed in hESCs, while SSEA-1 is expressed in mESCs; (3) the self-renewal of hESCs is dependent on FGF/TGFβ signaling pathways, while mESCs use leukemia inhibitory factor (LIF)/BMP4 signaling pathways for their self-renewal [58,64,65,68,69,70]
Summary
Early embryonic development can be divided into two stages, the pre-implantation stage and the post-implantation stage. Different stem cells from both pre-implantation and post-implantation embryos can be cultured in vitro and still maintain their differentiation potential in vivo. Both animal and cell culture models greatly facilitate our understanding of key events during this earliest stage of life. Substantial evidence demonstrates that miRNAs and endo-siRNAs participate in early embryogenesis in mice. Both in vitro and in vivo models suggest that miRNAs exert biological effects through regulating the self-renewal and differentiation of stem cells in/from early embryos. Since functions of miRNAs in pluripotent stem cells are well-covered elsewhere [8], in this review, we will focus on comparing in vivo and in vitro roles of miRNAs in regulating the potential of stem cells during early embryogenesis in mice and humans
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