Lee, SI, Lee, BR, Hwang, YS, Lee, HC, Rengaraj, D, Song, G et al.. MicroRNA-mediated posttranscriptional regulation is required for maintaining undifferentiated properties of blastoderm and primordial germ cells in chickens. Proc Natl Acad Sci USA 108: 10426-10431

World Class University Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Korea.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 06/2011; 108(26):10426-31. DOI: 10.1073/pnas.1106141108
Source: PubMed


MicroRNAs (miRNAs) play a critical role in determining the differentiation fate of pluripotent stem cells and germ cells in mammals. However, the mechanism(s) of miRNA-mediated posttranscriptional regulation with regard to lineage specification and differentiation in chick development require further investigation. Therefore, we conducted miRNA expression profiling to explore specific miRNA signatures in undifferentiated blastoderm and primordial germ cells (PGCs). We identified seven miRNAs that are highly expressed in blastoderm and 10 that are highly expressed in PGCs. In this study, miR-302a and miR-456 for blastoderm and miR-181a* for PGCs were analyzed further for their target transcripts and regulatory pathways. Both miR-302a and miR-456 bound directly to the sex-determining region Y box 11 transcript and could act as posttranscriptional coregulators to maintain the undifferentiated state of the chicken blastoderm through the suppression of somatic gene expression and differentiation. Moreover, miR-181a* showed a bifunctional role in PGCs by binding to two different transcripts. miR-181a* inhibited the somatic differentiation of PGCs by silencing homeobox A1 expression. Additionally, miR-181a* prevented PGCs from entering meiosis through the repression of the nuclear receptor subfamily 6, group A, member 1 transcript. Collectively, our data demonstrate that in chickens miRNAs intrinsically regulate the differentiation fate of blastoderms and PGCs and that the specific timing of germ cell meiosis is controlled through miRNA expression.

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    • "Cells HOXA1 and PGC meiosis by targeting NR6A1 (Lee et al., 2011). Although such studies demonstrate that miRNAs play an essential role in the regulation of gene expression during PGC development, the function of miRNAs and the regulatory network of their target mRNAs remain unclear. "
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    ABSTRACT: Non-coding microRNAs (miRNAs) regulate the translation of target messenger RNAs (mRNAs) involved in the growth and development of a variety of cells, including primordial germ cells (PGCs) which play an essential role in germ cell development. However, the target mRNAs and the regulatory networks influenced by miRNAs in PGCs remain unclear. Here, we demonstrate a novel miRNAs control PGC development through targeting mRNAs involved in various cellular pathways. We reveal the PGC-enriched expression patterns of nine miRNAs, including miR-10b, -18a, -93, -106b, -126-3p, -127, -181a, -181b, and -301, using miRNA expression analysis along with mRNA microarray analysis in PGCs, embryonic gonads, and postnatal testes. These miRNAs are highly expressed in PGCs, as demonstrated by Northern blotting, miRNA in situ hybridization assay, and miRNA qPCR analysis. This integrative study utilizing mRNA microarray analysis and miRNA target prediction demonstrates the regulatory networks through which these miRNAs regulate their potential target genes during PGC development. The elucidated networks of miRNAs disclose a coordinated molecular mechanism by which these miRNAs regulate distinct cellular pathways in PGCs that determine germ cell development.1.
    Full-text · Article · Oct 2015 · Moleculer Cells
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    • "Establishment of a long-term culture system for chicken PGCs using basic FGF-containing medium (Choi et al., 2010; Macdonald et al., 2010) was followed by production of transgenic chickens via transplantation of cultured PGCs (Macdonald et al., 2012; Park and Han, 2012; Park et al., 2015). Furthermore, several studies based on long-term PGC culture systems have aimed to identify specific genetic and epigenetic mechanisms in PGCs, which is difficult in other species (Lee et al., 2011; Rengaraj et al., 2011; 2014). "
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    ABSTRACT: Production of genome-edited animals using germlinecompetent cells and genetic modification tools has provided opportunities for investigation of biological mechanisms in various organisms. The recently reported programmed genome editing technology that can induce gene modification at a target locus in an efficient and precise manner facilitates establishment of animal models. In this regard, the demand for genome-edited avian species, which are some of the most suitable model animals due to their unique embryonic development, has also increased. Furthermore, germline chimera production through longterm culture of chicken primordial germ cells (PGCs) has facilitated research on production of genome-edited chickens. Thus, use of avian germline modification is promising for development of novel avian models for research of disease control and various biological mechanisms. Here, we discuss recent progress in genome modification technology in avian species and its applications and future strategies.
    Full-text · Article · Sep 2015 · Moleculer Cells
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    • "In our results, the dre-miR-430a family (including dre-miR-430a, dre-miR-430b, dre-miR-430c and dre-miR-430i) is highly expressed from 512-cell to 6-somite stage, and may be functional in MZT (Figure 5C). Also, our results of dre-miR-456 and dre-miR-22a families are also consistent with the studies in the early development of chicken [36] and mouse [37], respectively. Moreover, we identified a number of known miRNAs reported to be involved in other processes may also play a potential role in embryonic development. "
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    ABSTRACT: During early vertebrate development, various small non-coding RNAs (sRNAs) such as MicroRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) are dynamically expressed for orchestrating the maternal-to-zygotic transition (MZT). Systematic analysis of expression profiles of zebrafish small RNAome will be greatly helpful for understanding the sRNA regulation during embryonic development. We first determined the expression profiles of sRNAs during eight distinct stages of early zebrafish development by sRNA-seq technology. Integrative analyses with a new computational platform of CSZ (characterization of small RNAome for zebrafish) demonstrated an sRNA class transition from piRNAs to miRNAs as development proceeds. We observed that both the abundance and diversity of miRNAs are gradually increased, while the abundance is enhanced more dramatically than the diversity during development. However, although both the abundance and diversity of piRNAs are gradually decreased, the diversity was firstly increased then rapidly decreased. To evaluate the computational accuracy, the expression levels of four known miRNAs were experimentally validated. We also predicted 25 potentially novel miRNAs, whereas two candidates were verified by Northern blots. Taken together, our analyses revealed the piRNA to miRNA transition as a conserved mechanism in zebrafish, although two different types of sRNAs exhibit distinct expression dynamics in abundance and diversity, respectively. Our study not only generated a better understanding for sRNA regulations in early zebrafish development, but also provided a useful platform for analyzing sRNA-seq data. The CSZ was implemented in Perl and freely downloadable at:
    Full-text · Article · Feb 2014 · BMC Genomics
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