Abstract
Single-cell measurements combined with mathematical modeling and computer simulations are powerful tools for understanding and exploring dynamical behaviors of gene networks and cellular functions that they control. Here, we describe experimental and computational methods to study cellular quiescence and its heterogeneity at the single-cell level.
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References
Coller HA, Sang L, Roberts JM (2006) A new description of cellular quiescence. PLoS Biol 4(3):e83. doi:10.1371/journal.pbio.0040083
Yao G (2014) Modelling mammalian cellular quiescence. Interface Focus 4:20130074
Augenlicht LH, Baserga R (1974) Changes in the G0 state of WI-38 fibroblasts at different times after confluence. Exp Cell Res 89(2):255–262
Owen TA, Soprano DR, Soprano KJ (1989) Analysis of the growth factor requirements for stimulation of WI-38 cells after extended periods of density-dependent growth arrest. J Cell Physiol 139(2):424–431. doi:10.1002/jcp.1041390227
Yanez I, O'Farrell M (1989) Variation in the length of the lag phase following serum restimulation of mouse 3T3 cells. Cell Biol Int Rep 13(5):453–462
Rodgers JT, King KY, Brett JO, Cromie MJ, Charville GW, Maguire KK, Brunson C, Mastey N, Liu L, Tsai CR, Goodell MA, Rando TA (2014) mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(alert). Nature 510(7505):393–396. doi:10.1038/nature13255. nature13255 [pii]
Llorens-Bobadilla E, Zhao S, Baser A, Saiz-Castro G, Zwadlo K, Martin-Villalba A (2015) Single-cell transcriptomics reveals a population of dormant neural stem cells that become activated upon brain injury. Cell Stem Cell 17(3):329–340. doi:10.1016/j.stem.2015.07.002. S1934-5909(15)00301-X [pii]
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70
Yao G, Lee TJ, Mori S, Nevins JR, You L (2008) A bistable Rb-E2F switch underlies the restriction point. Nat Cell Biol 10(4):476–482
Dong P, Maddali MV, Srimani JK, Thelot F, Nevins JR, Mathey-Prevot B, You L (2014) Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control. Nat Commun 5:4750
Stewart-Ornstein J, Lahav G (2016) Dynamics of CDKN1A in single cells defined by an endogenous fluorescent tagging toolkit. Cell Rep 14(7):1800–1811. doi:10.1016/j.celrep.2016.01.045. S2211-1247(16)30023-7 [pii]
Wong JV, Yao G, Nevins JR, You L (2011) Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC. Mol Cell 41(3):275–285. doi:10.1016/j.molcel.2011.01.014. S1097-2765(11)00041-4 [pii]
Wong JV, Yao G, Nevins JR, You LC (2011) Using noisy gene expression mediated by engineered adenovirus to probe signaling dynamics in mammalian cells. Methods Enzymol 497:221–237. doi:10.1016/B978-0-12-385075-1.00010-X
Yao G, Tan C, West M, Nevins JR, You L (2011) Origin of bistability underlying mammalian cell cycle entry. Mol Syst Biol 7:485. doi:10.1038/msb.2011.19. msb201119 [pii]
Tyson JJ, Baumann WT, Chen C, Verdugo A, Tavassoly I, Wang Y, Weiner LM, Clarke R (2011) Dynamic modelling of oestrogen signalling and cell fate in breast cancer cells. Nat Rev Cancer 11(7):523–532. doi:10.1038/nrc3081. nrc3081 [pii]
Aguda BD, Tang Y (1999) The kinetic origins of the restriction point in the mammalian cell cycle. Cell Prolif 32(5):321–335
Novak B, Tyson JJ (2004) A model for restriction point control of the mammalian cell cycle. J Theor Biol 230(4):563–579
Hoops S, Sahle S, Gauges R, Lee C, Pahle J, Simus N, Singhal M, Xu L, Mendes P, Kummer U (2006) COPASI–a COmplex PAthway SImulator. Bioinformatics 22(24):3067–3074. doi:10.1093/bioinformatics/btl485. btl485 [pii]
McAdams HH, Arkin A (1997) Stochastic mechanisms in gene expression. Proc Natl Acad Sci U S A 94(3):814–819
Hasty J, Pradines J, Dolnik M, Collins JJ (2000) Noise-based switches and amplifiers for gene expression. Proc Natl Acad Sci USA 97(5):2075–2080. doi:10.1073/pnas.040411297
Logan J, Nicolas JC, Topp WC, Girard M, Shenk T, Levine AJ (1981) Transformation by adenovirus early region 2A temperature-sensitive mutants and their revertants. Virology 115(2):419–422
Lee T, Yao G, Bennett DC, Nevins JR, You L (2010) Stochastic E2F activation and reconciliation of phenomenological cell-cycle models. PLoS Biol 8(9):e1000488. doi:10.1371/journal.pbio.1000488
Srimani JK, Yao G, Neu J, Tanouchi Y, Lee TJ, You L (2014) Linear population allocation by bistable switches in response to transient stimulation. PLoS One 9(8):e105408. doi:10.1371/journal.pone.0105408. PONE-D-14-22009 [pii]
Szymczak AL, Workman CJ, Wang Y, Vignali KM, Dilioglou S, Vanin EF, Vignali DA (2004) Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector. Nat Biotechnol 22(5):589–594. doi:10.1038/nbt957
Gillespie DT (2000) The chemical Langevin equation. J Chem Phys 113(1):297–306. doi:10.1063/1.481811
Acknowledgment
This work was supported by grants from the NSF (DMS-1463137 and DMS-1418172, to G.Y.), NIH (GM-084905, a T32 fellowship to J.S.K)Â and the NSF of China and Anhui Province (Grant No. 31500676 and 1508085SQC202, to X.W.).
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Kwon, J.S., Wang, X., Yao, G. (2018). Study Quiescence Heterogeneity by Coupling Single-Cell Measurements and Computer Modeling. In: Lacorazza, H. (eds) Cellular Quiescence. Methods in Molecular Biology, vol 1686. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7371-2_20
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DOI: https://doi.org/10.1007/978-1-4939-7371-2_20
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