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Cell cycle control of embryonic stem cells

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Abstract

Embryonic stem cells have the capacity for unlimited proliferation while retaining their potential to differentiate into a wide variety of cell types. Murine, primate and human embryonic stem cells (ESCs) exhibit a very unusual cell cycle structure, characterized by a short G1 phase and a high proportion of cells in S-phase. In the case of mESCs, this is associated with a unique mechanism of cell cycle regulation, underpinned by the precocious activity of cyclin dependent protein kinase (Cdk) activities. As ES cells differentiate, their cell cycle structure changes dramatically so as to incorporate a significantly longer G1 phase and their mechanism of cell cycle regulation changes to that typically seen in other mammalian cells. The unique cell cycle structure and mechanism of cell cycle control indicates that the cell cycle machinery plays a role in establishment or maintenance of the stem cell state. This idea is supported by the frequent involvement of cell cycle regulatory molecules in cell immortalization.

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References

  1. MacAuley A, Werb Z, Mirkes PE. Development 1993;117:873–883.

    CAS  Google Scholar 

  2. Stead E, White J, Faast R, et al. Oncogene 2002;21:8320–8333.

    PubMed  CAS  Google Scholar 

  3. Savatier P, Huang S, Szekely L, Wiman KG, Samarut J. Oncogene 1994;9:809–818.

    PubMed  CAS  Google Scholar 

  4. Mummery CL, van Rooijen MA, van den Brink SE, de Laat SW. Cell Differ 1987;20:153–160.

    PubMed  CAS  Google Scholar 

  5. Kranenburg O, de Groot RP, Van der Eb AJ, Zantema A. Oncogene 1995;10:87–95.

    PubMed  CAS  Google Scholar 

  6. Resnick JL, Bixler LS, Cheng L, Donovan PJ. Nature 1992;359(6395):550–551.

    PubMed  CAS  Google Scholar 

  7. Murray AW, Kirschner MW. Nature 1989;339:275–280.

    PubMed  CAS  Google Scholar 

  8. Yarden A, Geiger B. Dev Dyn 1996;206:1–11.

    PubMed  CAS  Google Scholar 

  9. Edgar BA, Lehner CF. Science 1996;274:1646–1652.

    PubMed  CAS  Google Scholar 

  10. Bartek J, Lukas J. Curr Opin Cell Biol 2001;13:738–747.

    PubMed  CAS  Google Scholar 

  11. Malumbres M, Barbacid M. Nat Rev Cancer 2001;1:222–231.

    PubMed  CAS  Google Scholar 

  12. Savatier P, Lapillonne H, van Grunsven LA, Rudkin BB, Samarut J. Oncogene 1996;12:309–322.

    PubMed  CAS  Google Scholar 

  13. Schratt G, Weinhold B, Lundberg AS, et al. Mol Cell Biol 2001;21(8):2933–2943.

    PubMed  CAS  Google Scholar 

  14. Ishimi Y, Komamura-Kohno Y. J Biol Chem 2001;276:34,428–34,433.

    CAS  Google Scholar 

  15. Furstenthal L, Kaiser BK, Swanson C, Jackson PK. J Cell Biol 2001;152:1267–1278.

    PubMed  CAS  Google Scholar 

  16. Coverley D, Laman H, Laskey RA. Nat Cell Biol 2002;4:523–528.

    PubMed  CAS  Google Scholar 

  17. Henneke G, Koundrioukoff S, Hubscher U. Oncogene 2003;22:4301–4313.

    PubMed  CAS  Google Scholar 

  18. Ohi R, Gould KL. Curr Opin Cell Biol 1999;11(2):267–273.

    PubMed  CAS  Google Scholar 

  19. Tyers M, Jorgensen P. Curr Opin Genet Dev 2000;10:54–64.

    PubMed  CAS  Google Scholar 

  20. Breeden LL. Curr Biol 2003;13:R31-R38.

    PubMed  CAS  Google Scholar 

  21. Quelle DE, Ashmun RA, Shurtleff SA, et al. Genes Dev 1993;7:1559–1571.

    PubMed  CAS  Google Scholar 

  22. Resnitzky D, Gossen M, Bujard H, Reed SI. Mol Cell Biol 1994;14:1669–1679.

    PubMed  CAS  Google Scholar 

  23. Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM, Pagano M. Mol Cell Biol 1995;15:2612–2624.

    PubMed  CAS  Google Scholar 

  24. Jeffrey PD, Russo AA, Polyak K, et al. Nature 1995;376:313–320.

    PubMed  CAS  Google Scholar 

  25. Matsuoka M, Kato JY, Fisher RP, Morgan DO, Sherr CJ. Mol Cell Biol 1994;14:7265–7275.

    PubMed  CAS  Google Scholar 

  26. Poon RY, Yamashita K, Adamczewski JP, Hunt T, Shuttleworth J. EMBO J 1993;12:3123–3132.

    PubMed  CAS  Google Scholar 

  27. Krek W, Nigg EA. EMBO J 1991;10:305–316.

    PubMed  CAS  Google Scholar 

  28. Krek W, Nigg EA. EMBO J 1991;10:3331–3341.

    PubMed  CAS  Google Scholar 

  29. Gu Y, Rosenblatt J, Morgan DO. EMBO J 1992;11:3995–4005.

    PubMed  CAS  Google Scholar 

  30. Pavletich NP. J Mol Biol 1999;287:821–828.

    PubMed  CAS  Google Scholar 

  31. Schreiber M, Kolbus A, Piu F, et al. Genes Dev 1999;13:607–619.

    PubMed  CAS  Google Scholar 

  32. Thullberg M, Bartkova J, Khan S, et al. FEBS Lett 2000;470:161–166.

    PubMed  CAS  Google Scholar 

  33. Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D, Barrett JC. Proc Natl Acad Sci USA 1996;93:13,742–13,747.

    CAS  Google Scholar 

  34. Zhu J, Woods D, McMahon M, Bishop JM. Genes Dev 1998;12:2997–3007.

    PubMed  CAS  Google Scholar 

  35. Passegue E, Wagner EF. EMBO J 2000;19:2969–2979.

    PubMed  CAS  Google Scholar 

  36. Kamb A, Gruis NA, Weaver-Feldhaus J, et al. Science 1994;264:436–440.

    PubMed  CAS  Google Scholar 

  37. Serrano M, Lee H, Chin L, Cordon-Cardo C, Beach D, DePinho RA. Cell 1996;85:27–37.

    PubMed  CAS  Google Scholar 

  38. Vidal A, Koff A. Gene 2000;247:1–15.

    PubMed  CAS  Google Scholar 

  39. Dulic V, Kaufmann WK, Wilson SJ, et al. Cell 1994;76:1013–1023.

    PubMed  CAS  Google Scholar 

  40. el-Deiry WS, Harper JW, O’Connor PM, et al. Cancer Res 1994;54:1169–1174.

    PubMed  CAS  Google Scholar 

  41. Cheng T, Rodrigues N, Shen H, et al. Science 2000;287:1804–1808.

    PubMed  CAS  Google Scholar 

  42. Macleod KF, Sherry N, Hannon G, et al. Genes Dev 1995;9:935–944.

    PubMed  CAS  Google Scholar 

  43. Missero C, Calautti E, Eckner R, et al. Proc Natl Acad Sci USA 1995;92:5451–5455.

    PubMed  CAS  Google Scholar 

  44. Polyak K, Kato JY, Solomon MJ, et al. Genes Dev 1994;8:9–22.

    PubMed  CAS  Google Scholar 

  45. Mitra J, Dai CY, Somasundaram K, et al. Mol Cell Biol 1999;19:3916–3928.

    PubMed  CAS  Google Scholar 

  46. Jiang H, Chou HS, Zhu L. Mol Cell Biol 1998;18:5284–5290.

    PubMed  CAS  Google Scholar 

  47. McConnell BB, Gregory FJ, Stott FJ, Hara E, Peters G. Mol Cell Biol 1999;19:1981–1989.

    PubMed  CAS  Google Scholar 

  48. Alevizopoulos K, Vlach J, Hennecke S, Amati B. EMBO J 1997;16:5322–5333.

    PubMed  CAS  Google Scholar 

  49. DeGregori J, Kowalik T, Nevins JR. Mol Cell Biol 1995;15:4215–4224.

    PubMed  CAS  Google Scholar 

  50. Muller H, Bracken AP, Vernell R, et al. Genes Dev 2001;15:267–285.

    PubMed  CAS  Google Scholar 

  51. Ren B, Cam H, Takahashi Y, et al. Genes Dev 2002;16:245–256.

    PubMed  CAS  Google Scholar 

  52. Polager S, Kalma Y, Berkovich E, Ginsberg D. Oncogene 2002;21:437–446.

    PubMed  CAS  Google Scholar 

  53. Rands GF. J Embryol Exp Morphol 1986;98:209–217.

    PubMed  CAS  Google Scholar 

  54. Power MA, Tam PP. Anat Embryol (Berl) 1993;187:493–504.

    CAS  Google Scholar 

  55. Solter D, Skreb N, Damjanov I. Exp Cell Res 1971;64:331–334.

    PubMed  CAS  Google Scholar 

  56. Snow MHL. J Embryol Exp Morphol 1997;42:293–303.

    Google Scholar 

  57. Hogan B, Beddington R, Constantini F, Lacy E. A Laboratory Manual Cold Spring Harbour Laboratory Press, Cold Spring Harbour, NY, 1994.

  58. Geng Y, Yu Q, Sicinska E, et al. Cell 2003;114:431–443.

    PubMed  CAS  Google Scholar 

  59. Parisi T, Beck AR, Rougier N, et al. EMBO J 2003;22:4794–4803.

    PubMed  CAS  Google Scholar 

  60. Ortega S, Prieto I, Odajima J, et al. Nat Genet 2003;35:25–31.

    PubMed  CAS  Google Scholar 

  61. Sicinski P, Donaher JL, Parker SB, et al. Cell 1995;82:621–630.

    PubMed  CAS  Google Scholar 

  62. Fantl V, Stamp G, Andrews A, Rosewell I, Dickson C. Genes Dev 1995;9:2364–2372.

    PubMed  CAS  Google Scholar 

  63. Ciemerych MA, Kenney AM, Sicinska E, et al. Genes Dev 2002;16:3277–3289.

    PubMed  CAS  Google Scholar 

  64. Liu D, Matzuk MM, Sung WK, Guo Q, Wang P, Wolgemuth DJ. Nat Genet 1998;20:377–380.

    PubMed  CAS  Google Scholar 

  65. Brandeis M, Rosewell I, Carrington M, et al. Proc Natl Acad Sci USA 1998;95:4344–4349.

    PubMed  CAS  Google Scholar 

  66. Murphy M, Stinnakre MG, Senamaud-Beaufort C, et al. Nat Genet 1997;15:83–86.

    PubMed  CAS  Google Scholar 

  67. Lee EY, Chang CY, Hu N, et al. Nature 1992;359:288–294.

    PubMed  CAS  Google Scholar 

  68. Lee MH, Williams BO, Mulligan G, et al. Genes Dev 1996;10:1621–1632.

    PubMed  CAS  Google Scholar 

  69. Clarke AR, Maandag ER, van Roon M, et al. Nature 1992;359:328–330.

    PubMed  CAS  Google Scholar 

  70. Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA. Nature 1992;359:295–300.

    PubMed  CAS  Google Scholar 

  71. Cobrinik D, Lee MH, Hannon G, et al. Genes Dev 1996;10:1633–1644.

    PubMed  CAS  Google Scholar 

  72. Yamasaki L, Jacks T, Bronson R, Goillot E, Harlow E, Dyson NJ. Cell 1996;85:537–548.

    PubMed  CAS  Google Scholar 

  73. Field SJ, Tsai FY, Kuo F, et al. Cell 1996;85:549–561.

    PubMed  CAS  Google Scholar 

  74. Lindeman GJ, Dagnino L, Gaubatz S, et al. Genes Dev 1998;12:1092–1098.

    PubMed  CAS  Google Scholar 

  75. Humbert PO, Rogers C, Ganiatsas S, et al. Mol Cell 2000;6:281–291.

    PubMed  CAS  Google Scholar 

  76. Humbert PO, Verona R, Trimarchi JM, Rogers C, Dandapani S, Lees JA. Genes Dev 2000;14:690–703.

    PubMed  CAS  Google Scholar 

  77. Rempel RE, Saenz-Robles MT, Storms R, et al. Mol Cell 2000;6:293–306.

    PubMed  CAS  Google Scholar 

  78. Faast R, White J, Cartwright P, Crocker L, Sarcevic B, Dalton S. Oncogene 2004;23:491–502.

    PubMed  CAS  Google Scholar 

  79. Wianny F, Real FX, Mummery CL, et al. Dev Dyn 1998;212:49–62.

    PubMed  CAS  Google Scholar 

  80. Keyomarsi K, Conte D, Jr, Toyofuku W, Fox MP. Oncogene 1995;11:941–950.

    PubMed  CAS  Google Scholar 

  81. Gray-Bablin J, Zalvide J, Fox MP, Knickerbocker CJ, DeCaprio JA, Keyomarsi K. Proc Natl Acad Sci USA 1996;93:15,215–15,220.

    CAS  Google Scholar 

  82. Schraml P, Bucher C, Bissig H, et al. J Pathol 2003;200:375–382.

    PubMed  CAS  Google Scholar 

  83. Resnitzky D, Reed SI. Mol Cell Biol 1995;15:3463–3469.

    PubMed  CAS  Google Scholar 

  84. Rempel RE, Sleight SB, Maller JL. J Biol Chem 1995;270:6843–6855.

    PubMed  CAS  Google Scholar 

  85. Hartley RS, Rempel RE, Maller JL. Dev Biol 1996;173:408–419.

    PubMed  CAS  Google Scholar 

  86. Newport J, Kirschner M. Cell 1982;30:675–686.

    PubMed  CAS  Google Scholar 

  87. Newport JW, Kirschner MW. Cell 1984;37:731–742.

    PubMed  CAS  Google Scholar 

  88. Kane DA, Kimmel CB. Development 1993;119:447–456.

    PubMed  CAS  Google Scholar 

  89. Kane DA, Warga RM, Kimmel CB. Nature 1992;360:735–737.

    PubMed  CAS  Google Scholar 

  90. Edgar BA, Schubiger G. Cell 1986;44:871–877.

    PubMed  CAS  Google Scholar 

  91. Edgar BA, Sprenger F, Duronio RJ, Leopold P, O’Farrell PH. Genes Dev 1994;8:440–452.

    PubMed  CAS  Google Scholar 

  92. Foe VE, Alberts BM. J Cell Sci 1983;61:31–70.

    PubMed  CAS  Google Scholar 

  93. Stiffler LA, Ji JY, Trautmann S, Trusty C, Schubiger G. Development 1999;126:5505–5513.

    PubMed  CAS  Google Scholar 

  94. Richardson HE, O’Keefe LV, Reed SI, Saint R. Development 1993;119:673–690.

    PubMed  CAS  Google Scholar 

  95. White J, Stead E, Faast R, Conn S, Cartwright P, Dalton S. Developmental activation of the Rb-E2F pathway and establishment of cell cycle regulated Cdk activity during embryonic stem cell diferentiation. Mol Biol Cell 2005;16:2018–2027.

    PubMed  CAS  Google Scholar 

  96. Cho RJ, Huang M, Campbell MJ, et al. Nature Genetics 2001;27(1):48–54.

    PubMed  CAS  Google Scholar 

  97. Whitfield ML, Sherlock G, Saldanha AJ, et al. Mol Biol Cell 2002;13(6):1977–2000.

    PubMed  CAS  Google Scholar 

  98. Rao RR, Calhoun JD, Qin X, Rekaya R, Clark JK, Stice SL. Biotechnol Bioeng 2004;88:273–286.

    PubMed  CAS  Google Scholar 

  99. Sato N, Sanjuan IM, Heke M, Uchida M, Naef F, Brivanlou AH. Dev Biol 2003;260:404–413.

    PubMed  CAS  Google Scholar 

  100. Sage J, Mulligan GJ, Attardi LD, et al. Genes Dev 2000;14:3037–3050.

    PubMed  CAS  Google Scholar 

  101. Dannenberg JH, van Rossum A, Schuijff L, te Riele H. Genes Dev 2000;14:3051–3064.

    PubMed  CAS  Google Scholar 

  102. Hinds PW, Mittnacht S, Dulic V, Arnold A, Reed SI, Weinberg RA. Cell 1992;70:993–1006.

    PubMed  CAS  Google Scholar 

  103. He TC, Sparks AB, Rago C, et al. Science 1998;281(5382):1509–1512.

    PubMed  CAS  Google Scholar 

  104. Roussel MF. Adv Cancer Res 1998;74:1–24.

    PubMed  CAS  Google Scholar 

  105. Burdon T, Smith A, Savatier P. Trends Cell Biol 2002;12:432–438.

    PubMed  CAS  Google Scholar 

  106. Liang J, Slingerland JM. Cell Cycle 2003;2(4):339–345

    PubMed  CAS  Google Scholar 

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  1. Department of Molecular Biosciences, University of Adelaide, 5005, South Australia

    Josephine White

  2. Department of Biochemistry and Molecular Biology, University of Georgia, Green St., 30602, Athens, GA

    Stephen Dalton

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  2. Stephen Dalton
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Correspondence to Stephen Dalton.

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White, J., Dalton, S. Cell cycle control of embryonic stem cells. Stem Cell Rev 1, 131–138 (2005). https://doi.org/10.1385/SCR:1:2:131

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