Mean-Independent Noise Control of Cell Fates Via Intermediate States

Overview

Journal iScience

Publisher Cell Press

Date 2018 Nov 15

PMID 30428314

Citations 6

Authors

Christopher Rackauckas

Thomas Schilling

Qing Nie

Affiliations

Soon will be listed here.

Abstract

Stochasticity affects accurate signal detection and robust generation of correct cell fates. Although many known regulatory mechanisms may reduce fluctuations in signals, most simultaneously influence their mean dynamics, leading to unfaithful cell fates. Through analysis and computation, we demonstrate that a reversible signaling mechanism acting through intermediate states can reduce noise while maintaining the mean. This mean-independent noise control (MINC) mechanism is investigated in the context of an intracellular binding protein that regulates retinoic acid (RA) signaling during zebrafish hindbrain development. By comparing our models with experimental data, we find that the MINC mechanism allows for sharp boundaries of gene expression without sacrificing boundary accuracy. In addition, this MINC mechanism can modulate noise to levels that we show are beneficial to spatial patterning through noise-induced cell fate switching. These results reveal a design principle that may be important for noise regulation in many systems that control cell fate determination.

Citing Articles

Multiple morphogens and rapid elongation promote segmental patterning during development.

Qiu Y, Fung L, Schilling T, Nie Q PLoS Comput Biol. 2021; 17(6):e1009077.

PMID: 34161317 PMC: 8259987. DOI: 10.1371/journal.pcbi.1009077.

Inference and multiscale model of epithelial-to-mesenchymal transition via single-cell transcriptomic data.

Sha Y, Wang S, Zhou P, Nie Q Nucleic Acids Res. 2020; 48(17):9505-9520.

PMID: 32870263 PMC: 7515733. DOI: 10.1093/nar/gkaa725.

STOCHASTIC DYNAMICS OF CELL LINEAGE IN TISSUE HOMEOSTASIS.

Qiu Y, Chen W, Nie Q Discrete Continuous Dyn Syst Ser B. 2020; 24(8):3971-3994.

PMID: 32269502 PMC: 7141575. DOI: 10.3934/dcdsb.2018339.

Recent insights on the role and regulation of retinoic acid signaling during epicardial development.

Wang S, Moise A Genesis. 2019; 57(7-8):e23303.

PMID: 31066193 PMC: 6682438. DOI: 10.1002/dvg.23303.

Mechanical Communication Acts as a Noise Filter.

Viner H, Nitsan I, Sapir L, Drori S, Tzlil S iScience. 2019; 14:58-68.

PMID: 30927696 PMC: 6441679. DOI: 10.1016/j.isci.2019.02.030.

References

Kimmel C, Warga R, Kane D . Cell cycles and clonal strings during formation of the zebrafish central nervous system. Development. 1994; 120(2):265-76. DOI: 10.1242/dev.120.2.265. View

Kepler T, Elston T . Stochasticity in transcriptional regulation: origins, consequences, and mathematical representations. Biophys J. 2001; 81(6):3116-36. PMC: 1301773. DOI: 10.1016/S0006-3495(01)75949-8. View

Raj A, van Oudenaarden A . Nature, nurture, or chance: stochastic gene expression and its consequences. Cell. 2008; 135(2):216-26. PMC: 3118044. DOI: 10.1016/j.cell.2008.09.050. View

Koseska A, Zaikin A, Kurths J, Garcia-Ojalvo J . Timing cellular decision making under noise via cell-cell communication. PLoS One. 2009; 4(3):e4872. PMC: 2652718. DOI: 10.1371/journal.pone.0004872. View

Sosnik J, Zheng L, Rackauckas C, Digman M, Gratton E, Nie Q . Noise modulation in retinoic acid signaling sharpens segmental boundaries of gene expression in the embryonic zebrafish hindbrain. Elife. 2016; 5:e14034. PMC: 4829421. DOI: 10.7554/eLife.14034. View

Holloway D, Lopes F, da Fontoura Costa L, Travencolo B, Golyandina N, Usevich K . Gene expression noise in spatial patterning: hunchback promoter structure affects noise amplitude and distribution in Drosophila segmentation. PLoS Comput Biol. 2011; 7(2):e1001069. PMC: 3033364. DOI: 10.1371/journal.pcbi.1001069. View

Wu M, Su R, Li X, Ellis T, Lai Y, Wang X . Engineering of regulated stochastic cell fate determination. Proc Natl Acad Sci U S A. 2013; 110(26):10610-5. PMC: 3696818. DOI: 10.1073/pnas.1305423110. View

Gregor T, Tank D, Wieschaus E, Bialek W . Probing the limits to positional information. Cell. 2007; 130(1):153-64. PMC: 2253670. DOI: 10.1016/j.cell.2007.05.025. View

White R, Nie Q, Lander A, Schilling T . Complex regulation of cyp26a1 creates a robust retinoic acid gradient in the zebrafish embryo. PLoS Biol. 2007; 5(11):e304. PMC: 2080651. DOI: 10.1371/journal.pbio.0050304. View

10.

Wartlick O, Kicheva A, Gonzalez-Gaitan M . Morphogen gradient formation. Cold Spring Harb Perspect Biol. 2010; 1(3):a001255. PMC: 2773637. DOI: 10.1101/cshperspect.a001255. View

11.

Gupta A, Hepp B, Khammash M . Noise Induces the Population-Level Entrainment of Incoherent, Uncoupled Intracellular Oscillators. Cell Syst. 2016; 3(6):521-531.e13. DOI: 10.1016/j.cels.2016.10.006. View

12.

Keren L, van Dijk D, Weingarten-Gabbay S, Davidi D, Jona G, Weinberger A . Noise in gene expression is coupled to growth rate. Genome Res. 2015; 25(12):1893-902. PMC: 4665010. DOI: 10.1101/gr.191635.115. View

13.

Elowitz M, Levine A, Siggia E, Swain P . Stochastic gene expression in a single cell. Science. 2002; 297(5584):1183-6. DOI: 10.1126/science.1070919. View

14.

Schilling T, Nie Q, Lander A . Dynamics and precision in retinoic acid morphogen gradients. Curr Opin Genet Dev. 2012; 22(6):562-9. PMC: 3790664. DOI: 10.1016/j.gde.2012.11.012. View

15.

Ta C, Nie Q, Hong T . Controlling Stochasticity in Epithelial-Mesenchymal Transition Through Multiple Intermediate Cellular States. Discrete Continuous Dyn Syst Ser B. 2018; 21(7):2275-2291. PMC: 5828240. DOI: 10.3934/dcdsb.2016047. View

16.

Sirbu I, Gresh L, Barra J, Duester G . Shifting boundaries of retinoic acid activity control hindbrain segmental gene expression. Development. 2005; 132(11):2611-22. PMC: 2833012. DOI: 10.1242/dev.01845. View

17.

Rackauckas C, Nie Q . ADAPTIVE METHODS FOR STOCHASTIC DIFFERENTIAL EQUATIONS VIA NATURAL EMBEDDINGS AND REJECTION SAMPLING WITH MEMORY. Discrete Continuous Dyn Syst Ser B. 2018; 22(7):2731-2761. PMC: 5844583. DOI: 10.3934/dcdsb.2017133. View

18.

van Galen P, Kreso A, Wienholds E, Laurenti E, Eppert K, Lechman E . Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion. Cell Stem Cell. 2014; 14(1):94-106. DOI: 10.1016/j.stem.2013.11.021. View

19.

Niederreither K, Dolle P . Retinoic acid in development: towards an integrated view. Nat Rev Genet. 2008; 9(7):541-53. DOI: 10.1038/nrg2340. View

20.

Thattai M, van Oudenaarden A . Intrinsic noise in gene regulatory networks. Proc Natl Acad Sci U S A. 2001; 98(15):8614-9. PMC: 37484. DOI: 10.1073/pnas.151588598. View