Russian version English version
Volume 9   Issue 2   Year 2014
Akberdin I.R., Ivanisenko N.V., Kazantsev F.V., Oschepkova E.A., Omelyanchuk N.A., Matushkin Yu.G., Afonnikov D.A.

Modeling of Regulatory Mechanisms for mESC Self-Renewal: Kinetic and Stochastic Approaches

Mathematical Biology & Bioinformatics. 2014;9(2):504-517.

doi: 10.17537/2014.9.504.


  1. Medvedev SP, Shevchenko AI, Sukhikh GT, Zakiian SM. Indutsirovannye pliuripotentnye stvolovye kletki (Induced pluripotent stem cells). Ed. Vlasova V.V. Novosibirsk; 2014. 368 p. (in Russ.).
  2. Jaenisch R, Young R. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell. 2008;132(4):567-582. doi: 10.1016/j.cell.2008.01.015
  3. Graf T, Stadtfeld M. Heterogeneity of embryonic and adult stem cells. Cell Stem Cell. 2008;3(5):480-483. doi: 10.1016/j.stem.2008.10.007
  4. MacArthur BD, Lemischka IR. Statistical mechanics of pluripotency. Cell. 2013;154(3):484-489. doi: 10.1016/j.cell.2013.07.024
  5. Hayashi K, Lopes SM, Tang F, Surani MA. Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states. Cell Stem Cell. 2008;3(4):391-401. doi: 10.1016/j.stem.2008.07.027
  6. Torres-Padilla ME, Chambers I. Transcription factor heterogeneity in pluripotent stem cells: a stochastic advantage. Development. 2014;141(11):2173-2181. doi: 10.1242/dev.102624
  7. Akberdin IR, Kazantsev FV, Ermak TV, Timonov VS, Khlebodarova TM, Likhoshvai VA. In Silico Cell: Challenges and Perspectives. Matematicheskaya biologiya i bioinformatika (Mathematical Biology and Bioinformatics). 2013;8(1):295-315 (in Russ.). doi: 10.17537/2013.8.295
  8. Kalmar T, Lim C, Hayward P, Muñoz-Descalzo S, Nichols J, Garcia-Ojalvo J, Martinez Arias A. Regulated fluctuations in Nanog expression mediate cell fate decisions in embryonic stem cells. PLoS Biol. 2009;7(7):e1000149. doi: 10.1371/journal.pbio.1000149
  9. Glauche I, Herberg M, Roeder I. Nanog variability and pluripotency regulation of embryonic stem cells-insights from a mathematical model analysis. PLoS One. 2010;5(6):e11238. doi: 10.1371/journal.pone.0011238
  10. Wu J, Tzanakakis ES. Distinct allelic patterns of Nanog expression impart embryonic stem cell population heterogeneity. PLoS Comp. Biol. 2013;9(7):e1003140.
  11. Chickarmane V, Olariu V, Peterson C. Probing the role of stochasticity in a model of the embryonic stem cell-heterogeneous gene expression and reprogramming efficiency. BMC Syst. Biol. 2012;6(1):98. doi: 10.1186/1752-0509-6-98
  12. Chickarmane V, Troein C, Nuber UA, Sauro HM, Peterson C. Transcriptional dynamics of the embryonic stem cell switch. PLoS Comp. Biol. 2006;2(9):e123.
  13. Chickarmane V, Peterson C. A computational model for understanding stem cell, trophectoderm and endoderm lineage determination. PLoS One. 2008;3(10):e3478. doi: 10.1371/journal.pone.0003478
  14. Buchler NE, Gerland U, Hwa T. On schemes of combinatorial transcription logic. PNAS. 2003;100(9):5136-5141. doi: 10.1073/pnas.0930314100
  15. Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A. The ground state of embryonic stem cell self-renewal. Nature. 2008;453(7194):519-523. doi: 10.1038/nature06968
  16. Adachi K, Schöler HR. Directing reprogramming to pluripotency by transcription factors. Curr. Opin. Gen.&Dev. 2012;22(5):416-422.
  17. Fidalgo M, Faiola F, Pereira CF, Ding J, Saunders A, Gingold J, Schaniel C, Lemischka IR, Silva JC, Wang J. Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming. PNAS. 2012;109(40):16202-16207. doi: 10.1073/pnas.1208533109
  18. Wu J, Tzanakakis ES. Contribution of stochastic partitioning at human embryonic stem cell division to NANOG heterogeneity. PloS One. 2012;7(11):e50715. doi: 10.1371/journal.pone.0050715
  19. Navarro P, Festuccia N, Colby D, Gagliardi A, Mullin NP, Zhang W, Karwacki-Neisius V, Osorno R, Kelly D, Robertson M, Chambers I. OCT4/SOX2-independent Nanog autorepression modulates heterogeneous Nanog gene expression in mouse ES cells. The EMBO J. 2012;31(24):4547-4562. doi: 10.1038/emboj.2012.321
  20. Singh AM, Hamazaki T, Hankowski KE, Terada N. A heterogeneous expression pattern for Nanog in embryonic stem cells. Stem Cells. 2007;25(10):2534-2542. doi: 10.1634/stemcells.2007-0126
  21. Karwacki-Neisius V, Göke J, Osorno R, Halbritter F, Ng JH, Weiße AY, Wong FCK, Gagliardi A, Mullin NP, Festuccia N, Colby D, Tomlinson SR, Ng HH, Chambers I. Reduced Oct4 expression directs a robust pluripotent state with distinct signaling activity and increased enhancer occupancy by Oct4 and Nanog. Cell Stem Cell. 2013;12(5):531-545. doi: 10.1016/j.stem.2013.04.023
  22. Thomson M, Liu SJ, Zou LN, Smith Z, Meissner A, Ramanathan S. Pluripotency factors in embryonic stem cells regulate differentiation into germ layers. Cell. 2011;145(6):875-889. doi: 10.1016/j.cell.2011.05.017
  23. Abranches E, Bekman E, Henrique D. Generation and characterization of a novel mouse embryonic stem cell line with a dynamic reporter of Nanog expression. PloS One. 2013;8(3):e59928. doi: 10.1371/journal.pone.0059928
  24. Saxe JP, Tomilin A, Schöler HR, Plath K, Huang J. Post-translational regulation of Oct4 transcriptional activity. PloS One. 2009;4(2):e4467. doi: 10.1371/journal.pone.0004467
  25. Likhoshvai V, Ratushny A. Generalized hill function method for modeling molecular processes. J. Bioinform. Comput. Biol. 2007;5(02b):521-531. doi: 10.1142/S0219720007002837
  26. Gillespie DT. Stochastic simulation of chemical kinetics. Annu. Rev. Phys. Chem. 2007;58:35-55. doi: 10.1146/annurev.physchem.58.032806.104637
  27. Gillespie DT. Simulation methods in systems biology. In: Formal Methods for Computational Systems Biology. Eds. Bernardo M., Degano P., Zavattaro G. Springer Berlin Heidelberg; 2008. P. 125-167. doi: 10.1007/978-3-540-68894-5_5
  28. Rohr C, Marwan W, Heiner M. Snoopy - a unifying Petri net framework to investigate biomolecular networks. Bioinformatics. 2010;26(7):974-975. doi: 10.1093/bioinformatics/btq050
  29. Gillespie DT. Exact stochastic simulation of coupled chemical reactions. J. Phys. Chem. 1977;81(25):2340-2361. doi: 10.1021/j100540a008
  30. Papapetrou EP, Tomishima MJ, Chambers SM, Mica Y, Reed E, Menon J, Tabar V, Mo Q, Studer L, Sadelain M. Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation. PNAS. 2009;106(31):12759-12764. doi: 10.1073/pnas.0904825106
  31. Suzuki A, Raya Á, Kawakami Y, Morita M, Matsui T, Nakashima K, Gage FH, Rodríguez-Esteban C, Belmonte JCI. Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells. PNAS. 2006;103(27):10294-10299. doi: 10.1073/pnas.0506945103
Table of Contents Original Article
Math. Biol. Bioinf.
doi: 10.17537/2014.9.504
published in Russian

Abstract (rus.)
Abstract (eng.)
Full text (rus., pdf)


  Copyright IMPB RAS © 2005-2022