Browse > Article
http://dx.doi.org/10.14348/molcells.2015.0146

PGC-Enriched miRNAs Control Germ Cell Development  

Bhin, Jinhyuk (Department of Chemical Engineering, Pohang University of Science and Technology)
Jeong, Hoe-Su (Graduate School of Biomedical Science and Engineering, Department of Biomedical Science, Hanyang University)
Kim, Jong Soo (Graduate School of Biomedical Science and Engineering, Department of Biomedical Science, Hanyang University)
Shin, Jeong Oh (Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University, College of Dentistry)
Hong, Ki Sung (Graduate School of Biomedical Science and Engineering, Department of Biomedical Science, Hanyang University)
Jung, Han-Sung (Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University, College of Dentistry)
Kim, Changhoon (Graduate School of Biomedical Science and Engineering, Department of Biomedical Science, Hanyang University)
Hwang, Daehee (Department of Chemical Engineering, Pohang University of Science and Technology)
Kim, Kye-Seong (Graduate School of Biomedical Science and Engineering, Department of Biomedical Science, Hanyang University)
Publication Information
Molecules and Cells / v.38, no.10, 2015 , pp. 895-903 More about this Journal
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.
Keywords
bioinformatic analysis; in situ hybridization; male primordial germ cells; microarray; miRNAs;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Takada, S., Berezikov, E., Choi, Y.L., Yamashita, Y., and Mano, H. (2009). Potential role of miR-29b in modulation of Dnmt3a and Dnmt3b expression in primordial germ cells of female mouse embryos. RNA 15, 1507-1514.   DOI   ScienceOn
2 Tang, F. (2010). Small RNAs in mammalian germline: tiny for immortal. Differentiation 79, 141-146.   DOI   ScienceOn
3 Tong, M.H., Mitchell, D.A., McGowan, S.D., Evanoff, R., and Griswold, M.D. (2012). Two miRNA clusters, Mir-17-92 (Mirc1) and Mir-106b-25 (Mirc3), are involved in the regulation of spermatogonial differentiation in mice. Biol. Reprod. 86, 72.   DOI
4 Tran, D.H., Satou, K., and Ho, T.B. (2008). Finding microRNA regulatory modules in human genome using rule induction. BMC Bioinform. 9 Suppl 12, S5.
5 Wang, X. (2008). miRDB: a microRNA target prediction and functional annotation database with a wiki interface. RNA 14, 1012-1017.   DOI   ScienceOn
6 Watson, C.M., and Tam, P.P. (2001). Cell lineage determination in the mouse. Cell Struct Funct. 26, 123-129.   DOI   ScienceOn
7 Xu, F., Gao, Z., Zhang, J., Rivera, C.A., Yin, J., Weng, J., and Ye, J. (2010). Lack of SIRT1 (Mammalian Sirtuin 1) activity leads to liver steatosis in the $SIRT1^{+/-}$ mice: a role of lipid mobilization and inflammation. Endocrinology 151, 2504-2514.   DOI   ScienceOn
8 Zhang, Y., Hayashi, Y., Cheng, X., Watanabe, T., Wang, X., Taniguchi, N., and Honke, K. (2005). Testis-specific sulfoglycolipid, seminolipid, is essential for germ cell function in spermatogenesis. Glycobiology 15, 649-654.   DOI
9 Zhou, B., Li, C., Qi, W., Zhang, Y., Zhang, F., Wu, J.X., Hu, Y.N., Wu, D.M., Liu, Y., Yan, T.T., et al. (2012). Downregulation of miR- 181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity. Diabetologia 55, 2032-2043.   DOI   ScienceOn
10 Abe, K. (2007). Developmental program for pluripotential cells and primordial germ cells in mice. Tanpakushitsu Kakusan Koso 52, 2046-2053.
11 Banisch, T.U., Goudarzi, M., and Raz, E. (2012). Small RNAs in germ cell development. Curr. Topics Dev. Biol. 99, 79-113.   DOI   ScienceOn
12 Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297.   DOI   ScienceOn
13 Chen, C., Ridzon, D.A., Broomer, A.J., Zhou, Z., Lee, D.H., Nguyen, J.T., Barbisin, M., Xu, N.L., Mahuvakar, V.R., Andersen, M.R., et al. (2005). Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33, e179.   DOI   ScienceOn
14 Bjork, J.K., Sandqvist, A., Elsing, A.N., Kotaja, N., and Sistonen, L. (2010). miR-18, a member of Oncomir-1, targets heat shock transcription factor 2 in spermatogenesis. Development 137, 3177-3184.   DOI   ScienceOn
15 Bolstad, B.M., Irizarry, R.A., Astrand, M., and Speed, T.P. (2003). A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics19, 185-193.   DOI   ScienceOn
16 Chae, S., Ahn, B.Y., Byun, K., Cho, Y.M., Yu, M.H., Lee, B., Hwang, D., and Park, K.S. (2013). A systems approach for decoding mitochondrial retrograde signaling pathways. Sci. Signal. 6, rs4.
17 De Felici, M., Farini, D., and Dolci, S. (2009). In or out stemness: comparing growth factor signalling in mouse embryonic stem cells and primordial germ cells. Curr. Stem Cell Res. Ther. 4, 87-97.   DOI
18 Dyce, P.W., Toms, D., and Li, J. (2010). Stem cells and germ cells: microRNA and gene expression signatures. Histol. Histopathol. 25, 505-513.
19 Filipowicz, W., Bhattacharyya, S.N., and Sonenberg, N. (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat. Rev. Genet. 9, 102-114.   DOI
20 Fujimoto, H., Tadano-Aritomi, K., Tokumasu, A., Ito, K., Hikita, T., Suzuki, K., and Ishizuka, I. (2000). Requirement of seminolipid in spermatogenesis revealed by UDP-galactose: Ceramide galactosyltransferase-deficient mice. J. Biol. Chem. 275, 22623-22626.   DOI   ScienceOn
21 Hayashi, K., Chuva de Sousa Lopes, S.M., Kaneda, M., Tang, F., Hajkova, P., Lao, K., O′Carroll, D., Das, P.P., Tarakhovsky, A., Miska, E.A., et al. (2008). MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis. PLoS One 3, e1738.   DOI   ScienceOn
22 Griffiths-Jones, S., Grocock, R.J., van Dongen, S., Bateman, A. and Enright, A.J. (2006). miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 34, D140-144.   DOI   ScienceOn
23 Gupta, S., Read, D.E., Deepti, A., Cawley, K., Gupta, A., Oommen, D., Verfaillie, T., Matus, S., Smith, M.A., Mott, J.L., et al. (2012). Perk-dependent repression of miR-106b-25 cluster is required for ER stress-induced apoptosis. Cell Death Dis. 3, e333.   DOI   ScienceOn
24 Harris, T.A., Yamakuchi, M., Ferlito, M., Mendell, J.T., and Lowenstein, C.J. (2008). MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc. Natl. Acad. Sci. USA 105, 1516-1521.   DOI   ScienceOn
25 Honke, K., Hirahara, Y., Dupree, J., Suzuki, K., Popko, B., Fukushima, K., Fukushima, J., Nagasawa, T., Yoshida, N., Wada, Y., et al. (2002). Paranodal junction formation and spermatogenesis require sulfoglycolipids. Proc. Natl. Acad. Sci. USA 99, 4227-4232.   DOI   ScienceOn
26 Huang, J.C., Babak, T., Corson, T.W., Chua, G., Khan, S., Gallie, B.L., Hughes, T.R., Blencowe, B.J., Frey, B.J., and Morris, Q.D. (2007). Using expression profiling data to identify human microRNA targets. Nat. Methods 4, 1045-1049.   DOI   ScienceOn
27 Huang, P., Gong, Y., Peng, X., Li, S., Yang, Y., and Feng, Y. (2010). Cloning, identification, and expression analysis at the stage of gonadal sex differentiation of chicken miR-363 and 363*. Acta Biochim. Biophys. Sin (Shanghai) 42, 522-529.   DOI   ScienceOn
28 Jessberger, R. (2008). New insights into germ cell tumor formation. Horm. Metab. Res. 40, 342-346.   DOI   ScienceOn
29 Huang da, W., Sherman, B.T., and Lempicki, R.A. (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protocols 4, 44-57.
30 Jaskiewicz, L., and Filipowicz, W. (2008). Role of Dicer in posttranscriptional RNA silencing. Curr. Top Microbiol. Immunol. 320, 77-97.
31 Joung, J.G., Hwang, K.B., Nam, J.W., Kim, S.J., and Zhang, B.T. (2007). Discovery of microRNA-mRNA modules via populationbased probabilistic learning. Bioinformatics 23, 1141-1147.   DOI   ScienceOn
32 Kane, N.M., Thrasher, A.J., Angelini, G.D., and Emanueli, C. (2014). Concise review: MicroRNAs as modulators of stem cells and angiogenesis. Stem Cells 32, 1059-1066.   DOI   ScienceOn
33 Kloosterman, W.P., Wienholds, E., de Bruijn, E., Kauppinen, S., and Plasterk, R.H. (2006). In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes. Nat. Methods 3, 27-29.   DOI   ScienceOn
34 Kondoh, G., Murata, Y., Aozasa, K., Yutsudo, M., and Hakura, A. (1991). Very high incidence of germ cell tumorigenesis (seminomagenesis) in human papillomavirus type 16 transgenic mice. J. Virol. 65, 3335-3339.
35 Kucia, M., Machalinski, B., and Ratajczak, M.Z. (2006). The developmental deposition of epiblast/germ cell-line derived cells in various organs as a hypothetical explanation of stem cell plasticity? Acta Neurobiol. Exp. (Wars) 66, 331-341.
36 Lagos-Quintana, M., Rauhur, R., Lendeckel, W., and Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs. Science 294, 853-858.   DOI   ScienceOn
37 Liu, Z., Yang, D., Xie, P., Ren, G., Sun, G., Zeng, X., and Sun, X. (2012). MiR-106b and MiR-15b modulate apoptosis and angiogenesis in myocardial infarction. Cell. Physiol. Biochem. 29, 851-862.   DOI   ScienceOn
38 Lee, H.J., Suk, J.E., Patrick, C., Bae, E.J., Cho, J.H., Rho, S., Hwang, D., Masliah, E., and Lee, S.J. (2010). Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J. Biol. Chem. 285, 9262-9272.   DOI   ScienceOn
39 Lee, S.I., Lee, B.R., Hwang, Y.S., Lee, H.C., Rengaraj, D., Song, G., Park, T.S., and Han, J.Y. (2011). 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.   DOI   ScienceOn
40 Lewis, B.P., Burge, C.B., and Bartel, D.P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20.   DOI   ScienceOn
41 Livak, K.J., and Schmittgen, T.D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402-408.   DOI   ScienceOn
42 McLaren, A. (1992). Development of primordial germ cells in the mouse. Andrologia 24, 243-247.
43 McLaren, A. (2000). Germ and somatic cell lineages in the developing gonad. Mol. Cell. Endocrinol. 163, 3-9.   DOI   ScienceOn
44 McLaren, A. (2003). Primordial germ cells in the mouse. Dev. Biol. 262, 1-15.   DOI   ScienceOn
45 Peng, X., Li, Y., Walters, K.A., Rosenzweig, E.R., Lederer, S.L., Aicher, L.D., Proll, S., and Katze, M.G. (2009). Computational identification of hepatitis C virus associated microRNA-mRNA regulatory modules in human livers. BMC Genomics10, 373.   DOI   ScienceOn
46 Medeiros, L.A., Dennis, L.M., Gill, M.E., Houbaviy, H., Markoulaki, S., Fu, D., White, A.C., Kirak, O., Sharp, P.A., Page, D.C., et al. (2011). Mir-290-295 deficiency in mice results in partially penetrant embryonic lethality and germ cell defects. Proc. Natl. Acad. Sci. USA 108, 14163-14168.   DOI   ScienceOn
47 Olive, V., Jiang, I., and He, L. (2010). mir-17-92, a cluster of miRNAs in the midst of the cancer network. Int. J. Biochem. Cell Biol. 42, 1348-1354.   DOI   ScienceOn
48 Pal, R., Totey, S., Mamidi, M.K., and Bhat, V.S. (2009). Propensity of human embryonic stem cell lines during early stage of lineage specification controls their terminal differentiation into mature cell types. Exp. Biol. Med. 234, 1230-1243.   DOI   ScienceOn
49 Saunders, L.R., Sharma, A.D., Tawney, J., Nakagawa, M., Okita, K., Yamanaka, S., Willenbring, H., and Verdin, E. (2010). miRNAs regulate SIRT1 expression during mouse embryonic stem cell differentiation and in adult mouse tissues. Aging 2, 415-431.   DOI
50 Schmid, R., Grellscheid, S.N., Ehrmann, I., Dalgliesh, C., Danilenko, M., Paronetto, M.P., Pedrotti, S., Grellscheid, D., Dixon, R.J., Sette, C., et al. (2013). The splicing landscape is globally reprogrammed during male meiosis. Nucleic Acids Res. 41, 10170-10184.   DOI   ScienceOn
51 Sirotkin, A.V., Ovcharenko, D., Grossmann, R., Laukova, M., and Mlyncek, M. (2009). Identification of microRNAs controlling human ovarian cell steroidogenesis via a genome-scale screen. J. Cell. Physiol. 219, 415-420.   DOI   ScienceOn