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Population robustness arising from cellular heterogeneity
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Paszek, Pawel, Ryan, Sheila, Ashall, Louise, Sillitoe, Kate, Harper, Claire V., Spiller, David G., Rand, D. A. (David A.) and White, Michael R. H. (2010) Population robustness arising from cellular heterogeneity. Proceedings of the National Academy of Sciences of the United States of America, Vol.107 (No.25). pp. 11644-11649. doi:10.1073/pnas.0913798107 ISSN 0027-8424.
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Official URL: http://dx.doi.org/10.1073/pnas.0913798107
Abstract
Heterogeneity between individual cells is a common feature of dynamic cellular processes, including signaling, transcription, and cell fate; yet the overall tissue level physiological phenotype needs to be carefully controlled to avoid fluctuations. Here we show that in the NF-kappa B signaling system, the precise timing of a dual-delayed negative feedback motif [involving stochastic transcription of inhibitor kappa B (I kappa B)-alpha and -epsilon] is optimized to induce heterogeneous timing of NF-kappa B oscillations between individual cells. We suggest that this dual-delayed negative feedback motif enables NF-kappa B signaling to generate robust single cell oscillations by reducing sensitivity to key parameter perturbations. Simultaneously, enhanced cell heterogeneity may represent a mechanism that controls the overall coordination and stability of cell population responses by decreasing temporal fluctuations of paracrine signaling. It has often been thought that dynamic biological systems may have evolved to maximize robustness through cell-to-cell coordination and homogeneity. Our analyses suggest in contrast, that this cellular variation might be advantageous and subject to evolutionary selection. Alternative types of therapy could perhaps be designed to modulate this cellular heterogeneity.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre |
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| Journal or Publication Title: | Proceedings of the National Academy of Sciences of the United States of America | ||||
| Publisher: | National Academy of Sciences | ||||
| ISSN: | 0027-8424 | ||||
| Official Date: | 22 June 2010 | ||||
| Dates: |
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| Volume: | Vol.107 | ||||
| Number: | No.25 | ||||
| Number of Pages: | 6 | ||||
| Page Range: | pp. 11644-11649 | ||||
| DOI: | 10.1073/pnas.0913798107 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Medical Research Council (Great Britain) (MRC), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Engineering and Physical Sciences Research Council (EPSRC), European Union | ||||
| Grant number: | G0500346, BBF0059381/BBF0058141, EP/C544587/1, GR/S29256/01, 005137 |
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