Transcription factor heterogeneity in pluripotent stem cells: A stochastic advantage

Development (Cambridge)

Volumn 141, Issue 11, 2014, Pages 2173-2181

  Torres Padilla, Maria Elena ^a   Chambers, Ian ^b  

^a UNIVERSITÉ DE STRASBOURG   (France)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Embryonic stem cell (ESC); Epiblast; Heterogeneity; Monoallelic; Pluripotency; Transcription

Indexed keywords

KRUPPEL LIKE FACTOR 4; MESSENGER RNA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR NANOG; TRANSCRIPTION FACTOR SOX2;

CELL DIFFERENTIATION; CELL FATE; CELL HETEROGENEITY; CELL LEVEL; CELL POPULATION; CELL RENEWAL; CODON; DICTYOSTELIUM; DNA METHYLATION; DROSOPHILA; EMBRYONIC STEM CELL; FLUORESCENCE ACTIVATED CELL SORTING; HISTONE METHYLATION; HOMOLOGOUS RECOMBINATION; HUMAN; IMMUNOFLUORESCENCE; NONHUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN SYNTHESIS; REVIEW; SACCHAROMYCES CEREVISIAE; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; TRANSLATION INITIATION;

EMBRYONIC STEM CELL (ESC); EPIBLAST; HETEROGENEITY; MONOALLELIC; PLURIPOTENCY; TRANSCRIPTION;

ALLELES; ANIMALS; CELL DIFFERENTIATION; CELL LINEAGE; CELL NUCLEUS; EMBRYONIC STEM CELLS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENE REGULATORY NETWORKS; HOMEODOMAIN PROTEINS; HUMANS; MICE; MODELS, THEORETICAL; PLURIPOTENT STEM CELLS; PROMOTER REGIONS, GENETIC; SACCHAROMYCES CEREVISIAE; STOCHASTIC PROCESSES; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 84901473732     PISSN: 09501991     EISSN: 14779129     Source Type: Journal    
DOI: 10.1242/dev.102624     Document Type: Review

References (91)

1. Abranches, E., Bekman, E. and Henrique, D. (2013). Generation and characterization of a novel mouse embryonic stem cell line with a dynamic reporter of Nanog expression. PLoS ONE 8, e59928.
2. Ambrosetti, D.-C., Basilico, C. and Dailey, L. (1997). Synergistic activation of the fibroblast growth factor 4 enhancer by sox2 and oct-3 depends on protein-protein interactions facilitated by a specific spatial arrangement of factor binding sites. Mol. Cell. Biol. 17, 6321-6329.
3. Ashall, L., Horton, C. A., Nelson, D. E., Paszek, P., Harper, C. V., Sillitoe, K., Ryan, S., Spiller, D. G., Unitt, J. F., Broomhead, D. S. et al. (2009). Pulsatile stimulation determines timing and specificity of NF-kappaB-dependent transcription. Science 324, 242-246.
4. Beddington, R. S. (1983). Histogenetic and neoplastic potential of different regions of the mouse embryonic egg cylinder. J. Embryol. Exp. Morphol. 75, 189-204.
5. Brons, I. G. M., Smithers, L. E., Trotter, M. W. B., Rugg-Gunn, P., Sun, B., Chuva de Sousa Lopes, S.M., Howlett, S.K., Clarkson, A., Ahrlund-Richter, L., Pedersen, R. A. et al. (2007). Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448, 191-195.
6. Brook, F. A. and Gardner, R. L. (1997). The origin and efficient derivation of embryonic stem cells in the mouse. Proc. Natl. Acad. Sci. U.S.A. 94, 5709-5712.
7. Brookes, E. and Pombo, A. (2009). Modifications of RNA polymerase II are pivotal in regulating gene expression states. EMBO Rep. 10, 1213-1219.
8. Cahan, P. and Daley, G. Q. (2013). Origins and implications of pluripotent stem cell variability and heterogeneity. Nat. Rev. Mol. Cell Biol. 14, 357-368.
9. Canham, M. A., Sharov, A. A., Ko, M. S. H. and Brickman, J. M. (2010). Functional heterogeneity of embryonic stem cells revealed through translational amplification of an early endodermal transcript. PLoS Biol. 8, e1000379.
10. Chae, H.-D., Lee, M.-R. and Broxmeyer, H. E. (2012). 5-Aminoimidazole-4-carboxyamide ribonucleoside induces G(1)/S arrest and Nanog downregulation via p53 and enhances erythroid differentiation. Stem Cells 30, 140-149.
11. Chambers, I., Colby, D., Robertson, M., Nichols, J., Lee, S., Tweedie, S. and Smith, A. (2003). Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113, 643-655.
12. Chambers, I., Silva, J., Colby, D., Nichols, J., Nijmeijer, B., Robertson, M., Vrana, J., Jones, K., Grotewold, L. and Smith, A. (2007). Nanog safeguards pluripotency and mediates germline development. Nature 450, 1230-1234.
13. Chan, Y.-S., Göke, J., Ng, J.-H., Lu, X., Gonzales, K. A., Tan, C.-P., Tng, W.-Q., Hong, Z.-Z., Lim, Y.-S. and Ng, H.-H. (2013). Induction of a human pluripotent state with distinct regulatory circuitry that resembles preimplantation epiblast. Cell Stem Cell 13, 663-675.
14. Chazaud, C., Yamanaka, Y., Pawson, T. and Rossant, J. (2006). Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway. Dev. Cell 10, 615-624.
15. Chen, X., Fang, F., Liou, Y.-C. and Ng, H.-H. (2008). Zfp143 regulates Nanog through modulation of Oct4 binding. Stem Cells 26, 2759-2767.
16. Cheng, A. M., Saxton, T. M., Sakai, R., Kulkarni, S., Mbamalu, G., Vogel, W., Tortorice, C. G., Cardiff, R. D., Cross, J. C., Muller, W. J. et al. (1998). Mammalian Grb2 regulates multiple steps in embryonic development and malignant transformation. Cell 95, 793-803.
17. Core, L. J. and Lis, J. T. (2008). Transcription regulation through promoter-proximal pausing of RNA polymerase II. Science 319, 1791-1792.
18. Dan, J., Li, M., Yang, J., Li, J., Okuka, M., Ye, X. and Liu, L. (2013). Roles for Tbx3 in regulation of two-cell state and telomere elongation in mouse ES cells. Sci. Rep. 3, 3492.
19. Deng, Q., Ramskold, D., Reinius, B. and Sandberg, R. (2014). Single-cell RNAseq reveals dynamic, random monoallelic gene expression in mammalian cells. Science 343, 193-196.
20. Dietrich, J.-E. and Hiiragi, T. (2007). Stochastic patterning in the mouse preimplantation embryo. Development 134, 4219-4231.
21. Elowitz, M. B., Levine, A. J., Siggia, E. D. and Swain, P. S. (2002). Stochastic gene expression in a single cell. Science 297, 1183-1186.
22. Evans, M. J. and Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-156.
23. Faddah, D. A., Wang, H., Cheng, A. W., Katz, Y., Buganim, Y. and Jaenisch, R. (2013). Single-cell analysis reveals that expression of nanog is biallelic and equally variable as that of other pluripotency factors in mouse ESCs. Cell Stem Cell 13, 23-29.
24. Festuccia, N. and Chambers, I. (2011). Quantification of pluripotency transcription factor levels in embryonic stem cells by flow cytometry. Curr. Protoc. Stem Cell Biol. Chapter 1, Unit 1B 9.
25. Festuccia, N., Osorno, R., Halbritter, F., Karwacki-Neisius, V., Navarro, P., Colby, D., Wong, F., Yates, A., Tomlinson, S. R. and Chambers, I. (2012). Esrrb is a direct Nanog target gene that can substitute for Nanog function in pluripotent cells. Cell Stem Cell 11, 477-490.
26. Festuccia, N., Osorno, R., Wilson, V. and Chambers, I. (2013). The role of pluripotency gene regulatory network components in mediating transitions between pluripotent cell states. Curr. Opin. Genet. Dev. 23, 504-511.
27. Ficz, G., Hore, T. A., Santos, F., Lee, H. J., Dean, W., Arand, J., Krueger, F., Oxley, D., Paul, Y.-L., Walter, J. et al. (2013). FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency. Cell Stem Cell 13, 351-359.
28. Fidalgo, M., Faiola, F., Pereira, C.-F., Ding, J., Saunders, A., Gingold, J., Schaniel, C., Lemischka, I. R., Silva, J. C. R. and Wang, J. (2012). Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming. Proc. Natl. Acad. Sci. U.S.A. 109, 16202-16207.
29. Filipczyk, A., Gkatzis, K., Fu, J., Hoppe, P. S., Lickert, H., Anastassiadis, K. and Schroeder, T. (2013). Biallelic expression of nanog protein in mouse embryonic stem cells. Cell Stem Cell 13, 12-13.
30. Frankenberg, S., Gerbe, F., Bessonnard, S., Belville, C., Pouchin, P., Bardot, O. and Chazaud, C. (2011). Primitive endoderm differentiates via a three-step mechanism involving Nanog and RTK signaling. Dev. Cell 21, 1005-1013.
31. Gafni, O., Weinberger, L., Mansour, A. A., Manor, Y. S., Chomsky, E., Ben-Yosef, D., Kalma, Y., Viukov, S., Maza, I., Zviran, A. et al. (2013). Derivation of novel human ground state naive pluripotent stem cells. Nature 504, 282-286.
32. Garcia, H. G., Tikhonov, M., Lin, A. and Gregor, T. (2013). Quantitative imaging of transcription in living Drosophila embryos links polymerase activity to patterning. Curr. Biol. 23, 2140-2145.
33. Guo, G., Huss, M., Tong, G. Q., Wang, C., Li Sun, L., Clarke, N. D. and Robson, P. (2010). Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. Dev. Cell 18, 675-685.
34. Habibi, E., Brinkman, A. B., Arand, J., Kroeze, L. I., Kerstens, H. H., Matarese, F., Lepikhov, K., Gut, M., Brun-Heath, I., Hubner, N. C. et al. (2013). Wholegenome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells. Cell Stem Cell 13, 360-369.
35. Hansen, C. H. and van Oudenaarden, A. (2013). Allele-specific detection of single mRNA molecules in situ. Nat. Methods 10, 869-871.
36. Harper, C. V., Finkenstädt, B., Woodcock, D. J., Friedrichsen, S., Semprini, S., Ashall, L., Spiller, D. G., Mullins, J. J., Rand, D. A., Davis, J. R. E. et al. (2011). Dynamic analysis of stochastic transcription cycles. PLoS Biol. 9, e1000607.
37. Hatano, S.-y., Tada, M., Kimura, H., Yamaguchi, S., Kono, T., Nakano, T., Suemori, H., Nakatsuji, N. and Tada, T. (2005). Pluripotential competence of cells associated with Nanog activity. Mech. Dev. 122, 67-79.
38. Hayashi, K., Chuva de Sousa Lopes, S. M., Tang, F. and Surani, M. A. (2008). Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states. Cell Stem Cell 3, 391-401.
39. Jaenisch, R. and Young, R. (2008). Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132, 567-582.
40. Kalmar, T., Lim, C., Hayward, P., Muñoz-Descalzo, S., Nichols, J., Garcia-Ojalvo, J. and Martinez Arias, A. (2009). Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells. PLoS Biol. 7, e1000149.
41. Karwacki-Neisius, V., Göke, J., Osorno, R., Halbritter, F., Ng, J. H., Weisse, A. Y., Wong, F. C., Gagliardi, A., Mullin, N. P., Festuccia, N. et al. (2013). Reduced Oct4 expression directs a robust pluripotent state with distinct signaling activity and increased enhancer occupancy by Oct4 and Nanog. Cell Stem Cell 12, 531-545.
42. Kim, J., Chu, J., Shen, X., Wang, J. and Orkin, S. H. (2008). An extended transcriptional network for pluripotency of embryonic stem cells. Cell 132, 1049-1061.
43. Kleinsmith, L. J. and Pierce, G. B. (1964). Multipotentiality of single embryonal carcinoma cells. Cancer Res. 24, 1544-1552.
44. Kristensen, A. R., Gsponer, J. and Foster, L. J. (2013). Protein synthesis rate is the predominant regulator of protein expression during differentiation. Mol. Syst. Biol. 9, 689.
45. Kurimoto, K., Yabuta, Y., Ohinata, Y., Ono, Y., Uno, K.D., Yamada, R.G., Ueda, H.R. and Saitou, M. (2006). An improved single-cell cDNA amplification method for efficient high-density oligonucleotidemicroarray analysis. Nucleic AcidsRes. 34, e42.
46. Lackner, D. H., Schmidt, M. W., Wu, S., Wolf, D. A. and Bahler, J. (2012). Regulation of transcriptome, translation, and proteome in response to environmental stress in fission yeast. Genome Biol. 13, R25.
47. Leitch, H. G., McEwen, K. R., Turp, A., Encheva, V., Carroll, T., Grabole, N., Mansfield, W., Nashun, B., Knezovich, J. G., Smith, A. et al. (2013). Naive pluripotency is associated with global DNA hypomethylation. Nat. Struct. Mol. Biol. 20, 311-316.
48. Levine, M. and Davidson, E. H. (2005). Gene regulatory networks for development. Proc. Natl. Acad. Sci. U.S.A. 102, 4936-4942.
49. Li, G.-W. and Xie, X. S. (2011). Central dogma at the single-molecule level in living cells. Nature 475, 308-315.
50. Little, S. C., Tikhonov, M. and Gregor, T. (2013). Precise developmental gene expression arises from globally stochastic transcriptional activity. Cell 154, 789-800.
51. Loh, Y.-H., Wu, Q., Chew, J.-L., Vega, V. B., Zhang, W., Chen, X., Bourque, G., George, J., Leong, B., Liu, J. et al. (2006). The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat. Genet. 38, 431-440.
52. Luo, Y., Lim, C. L., Nichols, J., Martinez-Arias, A. and Wernisch, L. (2012). Cell signalling regulates dynamics of Nanog distribution in embryonic stem cell populations. J. R. Soc. Interface 10, 20120525.
53. MacArthur, B. D. and Lemischka, I. R. (2013). Statistical mechanics of pluripotency. Cell 154, 484-489.
54. MacArthur, B. D., Sevilla, A., Lenz, M., Müller, F.-J., Schuldt, B.M., Schuppert, A.A., Ridden, S. J., Stumpf, P. S., Fidalgo, M., Ma'ayan, A. et al. (2012). Nanogdependent feedback loops regulate murine embryonic stem cell heterogeneity. Nature Cell Biol. 14, 1139-1147.
55. Macfarlan, T. S., Gifford, W. D., Agarwal, S., Driscoll, S., Lettieri, K., Wang, J., Andrews, S. E., Franco, L., Rosenfeld, M. G., Ren, B. et al. (2011). Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A. Genes Dev. 25, 594-607.
56. Macfarlan, T. S., Gifford, W.D., Driscoll, S., Lettieri, K., Rowe, H. M., Bonanomi, D., Firth, A., Singer, O., Trono, D. andPfaff, S. L. (2012). Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 487, 57-63.
57. Marks, H., Kalkan, T., Menafra, R., Denissov, S., Jones, K., Hofemeister, H., Nichols, J., Kranz, A., Stewart, A. F., Smith, A. et al. (2012). The transcriptional and epigenomic foundations of ground state pluripotency. Cell 149, 590-604.
58. Martin, G. R. (1981). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. U.S.A. 78, 7634-7638.
59. Mitsui, K., Tokuzawa, Y., Itoh, H., Segawa, K., Murakami, M., Takahashi, K., Maruyama, M., Maeda, M. and Yamanaka, S. (2003). The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113, 631-642.
60. Miyanari, Y. and Torres-Padilla, M.-E. (2012). Control of ground-state pluripotency by allelic regulation of Nanog. Nature 483, 470-473.
61. Morgani, S. M., Canham, M. A., Nichols, J., Sharov, A. A., Migueles, R. P., Ko, M. S. H. and Brickman, J. M. (2013). Totipotent embryonic stem cells arise in ground-state culture conditions. Cell Rep. 3, 1945-1957.
62. Muramoto, T., Cannon, D., Gierlinski, M., Corrigan, A., Barton, G. J. and Chubb, J. R. (2012). Live imaging of nascent RNA dynamics reveals distinct types of transcriptional pulse regulation. Proc. Natl. Acad. Sci. U.S.A. 109, 7350-7355.
63. Najm, F. J., Chenoweth, J. G., Anderson, P. D., Nadeau, J. H., Redline, R. W., McKay, R. D. G. and Tesar, P. J. (2011). Isolation of epiblast stem cells from preimplantation mouse embryos. Cell Stem Cell 8, 318-325.
64. Navarro, P., Festuccia, N., Colby, D., Gagliardi, A., Mullin, N. P., Zhang, W., Karwacki-Neisius, V., Osorno, R., Kelly, D., Robertson, M. et al. (2012). OCT4/SOX2-independent Nanog autorepression modulates heterogeneous Nanog gene expression in mouse ES cells. EMBO J. 31, 4547-4562.
65. Nester, E. W. and Stocker, B. A. (1963). Biosynthetic latency in early stages of deoxyribonucleic acidtransformation in bacillus subtilis. J. Bacteriol. 86, 785-796.
66. Ng, H.-H. and Surani, M. A. (2011). The transcriptional and signalling networks of pluripotency. Nat. Cell Biol. 13, 490-496.
67. Nichols, J., Silva, J., Roode, M. and Smith, A. (2009). Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo. Development 136, 3215-3222.
68. Niwa, H., Ogawa, K., Shimosato, D. and Adachi, K. (2009). A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature 460, 118-122.
69. Osorno, R., Tsakiridis, A., Wong, F., Cambray, N., Economou, C., Wilkie, R., Blin, G., Scotting, P. J., Chambers, I. and Wilson, V. (2012). The developmental dismantling of pluripotency is reversed by ectopic Oct4 expression. Development 139, 2288-2298.
70. Paszek, P., Ryan, S., Ashall, L., Sillitoe, K., Harper, C. V., Spiller, D. G., Rand, D. A. andWhite, M. R. (2010). Population robustness arising fromcellular heterogeneity. Proc. Natl. Acad. Sci. U.S.A. 107, 11644-11649.
71. Pauklin, S. and Vallier, L. (2013). The cell-cycle state of stem cells determines cell fate propensity. Cell 155, 135-147.
72. Pina, C., Fugazza, C., Tipping, A. J., Brown, J., Soneji, S., Teles, J., Peterson, C. and Enver, T. (2012). Inferring rules of lineage commitment in haematopoiesis. Nat. Cell Biol. 14, 287-294.
73. Ptashne, M. and Gann, A. (2001). Transcription initiation: imposing specificity by localization. Essays Biochem. 37, 1-15.
74. Raj, A. and van Oudenaarden, A. (2008). Nature, nurture, or chance: stochastic gene expression and its consequences. Cell 135, 216-226.
75. Raj, A., Peskin, C. S., Tranchina, D., Vargas, D. Y. and Tyagi, S. (2006). Stochastic mRNA synthesis in mammalian cells. PLoS Biol. 4, e309.
76. Ramakrishna, S., Suresh, B., Lim, K.-H., Cha, B.-H., Lee, S.-H., Kim, K.-S. and Baek, K.-H. (2011). PEST motif sequence regulating human NANOG for proteasomal degradation. Stem Cells Dev. 20, 1511-1519.
77. Sanchez-Ripoll, Y., Bone, H. K., Owen, T., Guedes, A. M. V., Abranches, E., Kumpfmueller, B., Spriggs, R. V., Henrique, D. and Welham, M. J. (2013). Glycogen synthase kinase-3 inhibition enhances translation of pluripotencyassociated transcription factors to contribute to maintenance of mouse embryonic stem cell self-renewal. PLoS ONE 8, e60148.
78. Sigal, A., Milo, R., Cohen, A., Geva-Zatorsky, N., Klein, Y., Liron, Y., Rosenfeld, N., Danon, T., Perzov, N. and Alon, U. (2006). Variability and memory of protein levels in human cells. Nature 444, 643-646.
79. Silva, J. and Smith, A. (2008). Capturing pluripotency. Cell 132, 532-536.
80. Silva, J., Nichols, J., Theunissen, T.W., Guo, G., vanOosten, A. L., Barrandon, O., Wray, J., Yamanaka, S., Chambers, I. andSmith, A. (2009). Nanog is the gateway to the pluripotent ground state. Cell 138, 722-737.
81. Siminovitch, L., McCulloch, E. A. and Till, J. E. (1963). The distribution of colonyforming cells among spleen colonies. J. Cell. Physiol. 62, 327-336.
82. Tesar, P. J., Chenoweth, J. G., Brook, F. A., Davies, T. J., Evans, E. P., Mack, D. L., Gardner, R. L. and McKay, R. D. G. (2007). New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448, 196-199.
83. Toyooka, Y., Shimosato, D., Murakami, K., Takahashi, K. and Niwa, H. (2008). Identification and characterization of subpopulations in undifferentiated ES cell culture. Development 135, 909-918.
84. van den Berg, D. L. C., Zhang, W., Yates, A., Engelen, E., Takacs, K., Bezstarosti, K., Demmers, J., Chambers, I. and Poot, R. A. (2008). The Estrogen Related Receptor Beta interacts with Oct4 to positively regulate Nanog gene expression. Mol. Cell. Biol. 28, 5986-5995.
85. Williams, D. C., Jr, Cai, M. and Clore, G. M. (2004). Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1 Sox2 Hoxb1-DNA ternary transcription factor complex. J. Biol. Chem. 279, 1449-1457.
86. Wray, J., Kalkan, T., Gomez-Lopez, S., Eckardt, D., Cook, A., Kemler, R. and Smith, A. (2011). 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, 838-845.
87. Wu, J. and Tzanakakis, E. S. (2013). Distinct allelic patterns of nanog expression impart embryonic stem cell population heterogeneity. PLoS Comput. Biol. 9, e1003140.
88. Yamanaka, Y., Lanner, F. and Rossant, J. (2010). FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst. Development 137, 715-724.
89. Ying, Q.-L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P. and Smith, A. (2008). The ground state of embryonic stem cell selfrenewal. Nature 453, 519-523.
90. Zalzman, M., Falco, G., Sharova, L. V., Nishiyama, A., Thomas, M., Lee, S.-L., Stagg, C. A., Hoang, H. G., Yang, H.-T., Indig, F. E. et al. (2010). Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature 464, 858-863.
91. Zopf, C. J., Quinn, K., Zeidman, J. and Maheshri, N. (2013). Cell-cycle dependence of transcription dominates noise in gene expression. PLoS Comput. Biol. 9, e1003161.