Significant differences of function and expression of microRNAs between ground state and serum-cultured pluripotent stem cells

Ying Yan^{a, #},
Xi Yang^{a, #},
Ting-Ting Li^b,
Kai-Li Gu^a,
Jing Hao^a,
Qiang Zhang^a,
Yangming Wang^{a
, ,}

a.
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing 100871, China
b.
Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100871, China

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Corresponding author: E-mail address: yangming.wang@pku.edu.cn (Yangming Wang)

These authors contributed equally to this work.

摘要

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Abstract: Serum- and 2i-cultured embryonic stem cells (ESCs) show different epigenetic landscapes and transcriptomic profiles. The difference in the function and expression of microRNAs (miRNAs) between these two states remains unclear. Here, we showed that 2i- and serum-cultured ESCs exhibited distinctive miRNA expression profiles with >100 miRNAs differentially expressed, and the expression changes were largely due to transcriptional regulation. We further characterized the function of miRNAs differentially expressed under two conditions and found that ESCs exhibited higher degree of dependency on miRNAs for rapid proliferation; since or but not wild-type ESCs showed slower growth rate and more accumulation in the G1 phase under 2i than serum condition. More interestingly, introduction of various self-renewal-silencing miRNAs in wild-type or ESCs failed to silence the self-renewal in 2i medium, but regained the ability to silence the self-renewal upon the addition of serum. Our findings reveal significant differences in the expression and function of miRNAs between serum- and 2i-cultured ESCs.
- Embryonic stem cells /
- microRNAs /
- Ground pluripotency state /
- Self-renewal
These authors contributed equally to this work.
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参考文献(73)

[1]	Ambros, V. MicroRNAs and developmental timing Curr. Opin. Genet. Dev., 21 (2011),pp. 511-517
[2]	Babiarz, J.E., Ruby, J.G., Wang, Y. et al. Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs Genes Dev., 22 (2008),pp. 2773-2785
[3]	Bartel, D.P. MicroRNAs: target recognition and regulatory functions Cell, 136 (2009),pp. 215-233
[4]	Baskerville, S., Bartel, D.P. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes RNA, 11 (2005),pp. 241-247
[5]	Benetti, R., Gonzalo, S., Jaco, I. et al. Nat. Struct. Mol. Biol., 15 (2008),p. 998
[6]	Blair, K., Wray, J., Smith, A. The liberation of embryonic stem cells PLoS Genet., 7 (2011),p. e1002019
[7]	Buehr, M., Meek, S., Blair, K. et al. Capture of authentic embryonic stem cells from rat blastocysts Cell, 135 (2008),pp. 1287-1298
[8]	Burdon, T., Stracey, C., Chambers, I. et al. Suppression of SHP-2 and ERK signalling promotes self-renewal of mouse embryonic stem cells Dev. Biol., 210 (1999),pp. 30-43
[9]	Calabrese, J.M., Seila, A.C., Yeo, G.W. et al. RNA sequence analysis defines Dicer's role in mouse embryonic stem cells Proc. Natl. Acad. Sci. U. S. A., 104 (2007),pp. 18097-18102
[10]	Cao, Y., Guo, W.T., Tian, S. et al. miR-290/371-Mbd2-Myc circuit regulates glycolytic metabolism to promote pluripotency EMBO J., 34 (2015),pp. 609-623
[11]	Chan, Y.S., Goke, J., Ng, J.H. et al. Induction of a human pluripotent state with distinct regulatory circuitry that resembles preimplantation epiblast Cell Stem Cell, 13 (2013),pp. 663-675
[12]	Chen, J., Liu, H., Liu, J. et al. H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs Nat. Genet., 45 (2013),pp. 34-42
[13]	Davis, B.N., Hilyard, A.C., Lagna, G. et al. SMAD proteins control DROSHA-mediated microRNA maturation Nature, 454 (2008),pp. 56-61
[14]	Di Leva, G., Garofalo, M., Croce, C.M. MicroRNAs in cancer Annu. Rev. Pathol., 9 (2014),pp. 287-314
[15]	Dodsworth, B.T., Flynn, R., Cowley, S.A. The current state of naive human pluripotency Stem Cells, 33 (2015),pp. 3181-3186
[16]	Ebert, M.S., Sharp, P.A. Roles for microRNAs in conferring robustness to biological processes Cell, 149 (2012),pp. 515-524
[17]	Eisen, M.B., Spellman, P.T., Brown, P.O. et al. Cluster analysis and display of genome-wide expression patterns Proc. Natl. Acad. Sci. U. S. A., 95 (1998),pp. 14863-14868
[18]	Ficz, G., Hore, T.A., Santos, F. et al. FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency Cell Stem Cell, 13 (2013),pp. 351-359
[19]	Gafni, O., Weinberger, L., Mansour, A.A. et al. Derivation of novel human ground state naive pluripotent stem cells Nature, 504 (2013),pp. 282-286
[20]	Grabole, N., Tischler, J., Hackett, J.A. et al. Prdm14 promotes germline fate and naive pluripotency by repressing FGF signalling and DNA methylation EMBO Rep., 14 (2013),pp. 629-637
[21]	Gu, K.L., Zhang, Q., Yan, Y. et al. Pluripotency-associated miR-290/302 family of microRNAs promote the dismantling of naive pluripotency Cell Res., 26 (2016),pp. 350-366
[22]	Guo, W.T., Wang, X.W., Yan, Y.L. et al. Suppression of epithelial-mesenchymal transition and apoptotic pathways by miR-294/302 family synergistically blocks let-7-induced silencing of self-renewal in embryonic stem cells Cell Death Differ., 22 (2015),pp. 1158-1169
[23]	Habibi, E., Brinkman, A.B., Arand, J. et al. Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells Cell Stem Cell, 13 (2013),pp. 360-369
[24]	Hanna, J., Markoulaki, S., Mitalipova, M. et al. Metastable pluripotent states in NOD-mouse-derived ESCs Cell Stem Cell, 4 (2009),pp. 513-524
[25]	Hirabayashi, M., Kato, M., Kobayashi, T. et al. Establishment of rat embryonic stem cell lines that can participate in germline chimerae at high efficiency Mol. Reprod. Dev., 77 (2010),p. 94
[26]	Hishida, T., Nozaki, Y., Nakachi, Y. et al. Indefinite self-renewal of ESCs through Myc/Max transcriptional complex-independent mechanisms Cell Stem Cell, 9 (2011),pp. 37-49
[27]	Jouneau, A., Ciaudo, C., Sismeiro, O. et al. Naive and primed murine pluripotent stem cells have distinct miRNA expression profiles RNA, 18 (2012),pp. 253-264
[28]	Judson, R.L., Babiarz, J.E., Venere, M. et al. Embryonic stem cell-specific microRNAs promote induced pluripotency Nat. Biotechnol., 27 (2009),pp. 459-461
[29]	Kanellopoulou, C., Muljo, S.A., Kung, A.L. et al. Genes Dev., 19 (2005),pp. 489-501
[30]	Kawamata, M., Ochiya, T. Generation of genetically modified rats from embryonic stem cells Proc. Natl. Acad. Sci. U. S. A., 107 (2010),pp. 14223-14228
[31]	Kim, V.N., Han, J., Siomi, M.C. Biogenesis of small RNAs in animals Nat. Rev. Mol. Cell Biol., 10 (2009),pp. 126-139
[32]	Kozomara, A., Griffiths-Jones, S. miRBase: integrating microRNA annotation and deep-sequencing data Nucleic Acids Res., 39 (2011),pp. D152-D157
[33]	Kunath, T., Saba-El-Leil, M.K., Almousailleakh, M. et al. FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment Development, 134 (2007),pp. 2895-2902
[34]	Kuzmin, A., Han, Z., Golding, M.C. et al. Gene Expr. Patterns, 8 (2008),pp. 107-116
[35]	Langmead, B., Trapnell, C., Pop, M. et al. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome Genome Biol., 10 (2009),p. R25
[36]	Leitch, H.G., McEwen, K.R., Turp, A. et al. Naive pluripotency is associated with global DNA hypomethylation Nat. Struct. Mol. Biol., 20 (2013),pp. 311-316
[37]	Li, P., Tong, C., Mehrian-Shai, R. et al. Germline competent embryonic stem cells derived from rat blastocysts Cell, 135 (2008),pp. 1299-1310
[38]	Marks, H., Kalkan, T., Menafra, R. et al. The transcriptional and epigenomic foundations of ground state pluripotency Cell, 149 (2012),pp. 590-604
[39]	Melton, C., Blelloch, R. MicroRNA regulation of embryonic stem cell self-renewal and differentiation Adv. Exp. Med. Biol., 695 (2010),pp. 105-117
[40]	Melton, C., Judson, R.L., Blelloch, R. Opposing microRNA families regulate self-renewal in mouse embryonic stem cells Nature, 463 (2010),pp. 621-626
[41]	Mendell, J.T., Olson, E.N. MicroRNAs in stress signaling and human disease Cell, 148 (2012),pp. 1172-1187
[42]	Miri, K., Latham, K., Panning, B. et al. Development, 140 (2013),pp. 4480-4489
[43]	Murchison, E.P., Partridge, J.F., Tam, O.H. et al. Characterization of Dicer-deficient murine embryonic stem cells Proc. Natl. Acad. Sci. U. S. A., 102 (2005),pp. 12135-12140
[44]	Newman, M.A., Thomson, J.M., Hammond, S.M. Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing RNA, 14 (2008),pp. 1539-1549
[45]	Nichols, J., Jones, K., Phillips, J.M. et al. Validated germline-competent embryonic stem cell lines from nonobese diabetic mice Nat. Med., 15 (2009),pp. 814-818
[46]	Nichols, J., Smith, A. Pluripotency in the embryo and in culture Cold Spring Harb. Perspect. Biol., 4 (2012),p. a008128
[47]	Piskounova, E., Polytarchou, C., Thornton, J.E. et al. Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms Cell, 147 (2011),pp. 1066-1079
[48]	Rahl, P.B., Lin, C.Y., Seila, A.C. et al. c-Myc regulates transcriptional pause release Cell, 141 (2010),pp. 432-445
[49]	Saldanha, A.J. Java Treeview–extensible visualization of microarray data Bioinformatics, 20 (2004),pp. 3246-3248
[50]	Shi, R., Chiang, V.L. Facile means for quantifying microRNA expression by real-time PCR Biotechniques, 39 (2005),pp. 519-525
[51]	Singh, S.K., Kagalwala, M.N., Parker-Thornburg, J. et al. REST maintains self-renewal and pluripotency of embryonic stem cells Nature, 453 (2008),pp. 223-227
[52]	Sinkkonen, L., Hugenschmidt, T., Berninger, P. et al. Nat. Struct. Mol. Biol., 15 (2008),pp. 259-267
[53]	Stavridis, M.P., Lunn, J.S., Collins, B.J. et al. A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification Development, 134 (2007),pp. 2889-2894
[54]	Takashima, Y., Guo, G., Loos, R. et al. Resetting transcription factor control circuitry toward ground-state pluripotency in human Cell, 158 (2014),pp. 1254-1269
[55]	Tay, Y., Zhang, J., Thomson, A.M. et al. Nature, 455 (2008),pp. 1124-1128
[56]	Tay, Y.M., Tam, W.L., Ang, Y.S. et al. MicroRNA-134 modulates the differentiation of mouse embryonic stem cells, where it causes post-transcriptional attenuation of Nanog and LRH1 Stem Cells, 26 (2008),pp. 17-29
[57]	Theunissen, T.W., Powell, B.E., Wang, H. et al. Systematic identification of culture conditions for induction and maintenance of naive human pluripotency Cell Stem Cell, 15 (2014),pp. 471-487
[58]	Thornton, J.E., Chang, H.M., Piskounova, E. et al. Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7) RNA, 18 (2012),pp. 1875-1885
[59]	Valamehr, B., Robinson, M., Abujarour, R. et al. Platform for induction and maintenance of transgene-free hiPSCs resembling ground state pluripotent stem cells Stem Cell Rep., 2 (2014),pp. 366-381
[60]	Viswanathan, S.R., Daley, G.Q., Gregory, R.I. Selective blockade of microRNA processing by Lin28 Science, 320 (2008),pp. 97-100
[61]	Wang, J., Xie, G., Singh, M. et al. Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells Nature, 516 (2014),pp. 405-409
[62]	Wang, L., Feng, Z., Wang, X. et al. DEGseq: an R package for identifying differentially expressed genes from RNA-seq data Bioinformatics, 26 (2010),pp. 136-138
[63]	Wang, Y., Baskerville, S., Shenoy, A. et al. Embryonic stem cell-specific microRNAs regulate the G1-S transition and promote rapid proliferation Nat. Genet., 40 (2008),pp. 1478-1483
[64]	Wang, Y., Medvid, R., Melton, C. et al. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal Nat. Genet., 39 (2007),pp. 380-385
[65]	Wang, Y., Melton, C., Li, Y.P. et al. miR-294/miR-302 promotes proliferation, suppresses G1-S restriction point, and inhibits ESC differentiation through separable mechanisms Cell Rep., 4 (2013),pp. 99-109
[66]	Ware, C.B., Nelson, A.M., Mecham, B. et al. Derivation of naive human embryonic stem cells Proc. Natl. Acad. Sci. U. S. A., 111 (2014),pp. 4484-4489
[67]	Wray, J., Kalkan, T., Gomez-Lopez, S. et al. Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation Nat. Cell Biol., 13 (2011),pp. 838-845
[68]	Wray, J., Kalkan, T., Smith, A.G. The ground state of pluripotency Biochem. Soc. Trans., 38 (2010),pp. 1027-1032
[69]	Yamaji, M., Ueda, J., Hayashi, K. et al. PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells Cell Stem Ccell, 12 (2013),pp. 368-382
[70]	Ying, Q.L., Nichols, J., Chambers, I. et al. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3 Cell, 115 (2003),pp. 281-292
[71]	Ying, Q.L., Wray, J., Nichols, J. et al. The ground state of embryonic stem cell self-renewal Nature, 453 (2008),pp. 519-523
[72]	Yuan, H., Corbi, N., Basilico, C. et al. Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3 Genes Dev., 9 (1995),pp. 2635-2645
[73]	Zheng, G.X., Ravi, A., Gould, G.M. et al. Genome-wide impact of a recently expanded microRNA cluster in mouse Proc. Natl. Acad. Sci. U. S. A., 108 (2011),pp. 15804-15809