Non-genetic individuality: chance in the single cell

Spudich, John L.; Koshland, Daniel E.

doi:10.1038/262467a0

Cited by 489 publications

(417 citation statements)

References 23 publications

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“…It is useful to consider that we do not know whether a similar heterogeneity prevails in liquid cultures of bacteria. There is no clear evidence to show that suspension cultures are actually as homogeneous as is usually assumed, and examination of single cells by a variety of methods has revealed a wide range of individual differentiation (Henrici, 1928;Ellis & Delbrueck, 1939;Spudich & Koshland, 1976). Moreover, it is a rare culture which does not trace its ancestry back to an original inoculum (e.g.…”

Section: Discussionmentioning

confidence: 99%

The Use of Mudlac Transposons as Tools for Vital Staining to Visualize Clonal and Non-clonal Patterns of Organization in Bacterial Growth on Agar Surfaces

Shapiro¹

1984

Microbiology

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When a histochemical stain for /I-galactosidase activity is applied to growth of Gram-negative bacteria on agar medium, the pigmentation is non-uniform and capable of revealing internal colony organization into different cell types. Use of an Escherichia coti strain with a thermosensitive lac repressor indicates that colonies expand by addition of new cells at the periphery and that older cells which have synthesized P-galactosidase early in development remain in the centre. Mixed inocula of different strains show clonal exclusiveness as they proliferate outwards. Mudlac transposons can create genetic fusions that place P-galactosidase expression under a variety of regulatory systems. Stained surface cultures of E. coli and Pseudomonas putida strains carrying Mudlac insertions in plasmids reveal a variety of flower-li ke staining patterns. These patterns display both clonal (i.e. sectorial) and non-clonal (circular and radial) features which are heritable within a given strain. The non-clonal aspects of the patterns reflect phenotypic differentiation without genetic change. These observations indicate that bacterial growth on agar surfaces is a highly regulated process similar, in many respects, to the development of specific multicellular tissues and organisms.

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Section: Discussionmentioning

confidence: 99%

The Use of Mudlac Transposons as Tools for Vital Staining to Visualize Clonal and Non-clonal Patterns of Organization in Bacterial Growth on Agar Surfaces

Shapiro¹

1984

Microbiology

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“…For example, the swimming behavior of Escherichia coli cells varies greatly from cell to cell (4), and recent studies start to link this variability in swimming behavior to concentration fluctuations in regulatory proteins (5)(6)(7). It is an open question whether a similar variability can be observed in eukaryotic chemotactic cells, such as the slime mold Dictyostelium discoideum, which has the exquisite ability to sense and respond to shallow gradients of chemoattractants.…”

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Cellular asymmetry and individuality in directional sensing

Samadani

Mettetal

Oudenaarden

2006

Proc. Natl. Acad. Sci. U.S.A.

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It is generally assumed that single cells in an isogenic population, when exposed to identical environments, exhibit the same behavior. However, it is becoming increasingly clear that, even in a genetically identical population, cellular behavior can vary significantly among cells. Here we explore this variability in the gradientsensing response of Dictyostelium cells when exposed to repeated spatiotemporal pulses of chemoattractant. Our experiments show the response of a single cell to be highly reproducible from pulse to pulse. In contrast, a large variability in the response direction and magnitude is observed from cell to cell, even when different cells are exposed to the same pulse. First, these results indicate that the gradient-sensing network has inherent asymmetries that can significantly impact the ability of cells to faithfully sense the direction of extracellular signals (cellular asymmetry). Second, we find that the magnitude of this asymmetry varies greatly among cells. Some cells are able to accurately follow the direction of an extracellular stimulus, whereas, in other cells, the intracellular asymmetry dominates, resulting in a polarization axis that is independent of the direction of the extracellular cue (cellular individuality). We integrate these experimental findings into a model that treats the effective signal a cell detects as the product of the extracellular signal and the asymmetric intracellular signal. With this model we successfully predict the population response. This cellular individuality and asymmetry might fundamentally limit the fidelity of signal detection; in contrast, however, it might be beneficial by diversifying phenotypes in isogenic populations.T he low number of molecules involved in biological systems can lead to large stochastic effects and population heterogeneity even within a genetically identical population (1-3). For example, the swimming behavior of Escherichia coli cells varies greatly from cell to cell (4), and recent studies start to link this variability in swimming behavior to concentration fluctuations in regulatory proteins (5-7). It is an open question whether a similar variability can be observed in eukaryotic chemotactic cells, such as the slime mold Dictyostelium discoideum, which has the exquisite ability to sense and respond to shallow gradients of chemoattractants. In these spatially sensitive systems, signaling errors might be introduced in two different ways. First, the concentrations of intracellular signaling components might vary from cell to cell; second, spatial inhomogeneities or asymmetries in the cellular distributions of molecules might influence the ability of cells to sense slight spatial differences in the extracellular environment.To explore this question, we employ a quantitative approach to systematically study directional sensing in single Dictyostelium cells. Recent experiments have demonstrated that an extracellular signal induces spatial localization of several signaling proteins along the plasma membrane (8-12). The localiz...

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“…That cells can behave differently, despite uniform genetic and environmental conditions, has profound implications for our understanding of evolutionary processes (4,5), and of design principles of genetic networks (6). Nongenetic individuality in bacteria has been observed long ago in the response to external signals (7,8). Recently, the heterogeneous response of bacterial populations to antibiotics, termed bacterial persistence, has been linked to their inherent nongenetic variability.…”

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confidence: 99%

Single-cell protein induction dynamics reveals a period of vulnerability to antibiotics in persister bacteria

Gefen

Gabay

Mumcuoglu

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

144

153

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Phenotypic variability in populations of cells has been linked to evolutionary robustness to stressful conditions. A remarkable example of the importance of cell-to-cell variability is found in bacterial persistence, where subpopulations of dormant bacteria, termed persisters, were shown to be responsible for the persistence of the population to antibiotic treatments. Here, we use microfluidic devices to monitor the induction of fluorescent proteins under synthetic promoters and characterize the dormant state of single persister bacteria. Surprisingly, we observe that protein production does take place in supposedly dormant bacteria, over a narrow time window after the exit from stationary phase. Only thereafter does protein production stop, suggesting that differentiation into persisters fully develops over this time window and not during starvation, as previously believed. In effect, we observe that exposure of bacteria to antibiotics during this time window significantly reduces persistence.

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Non-genetic individuality: chance in the single cell

Cited by 489 publications

References 23 publications

The Use of Mudlac Transposons as Tools for Vital Staining to Visualize Clonal and Non-clonal Patterns of Organization in Bacterial Growth on Agar Surfaces

The Use of Mudlac Transposons as Tools for Vital Staining to Visualize Clonal and Non-clonal Patterns of Organization in Bacterial Growth on Agar Surfaces

Cellular asymmetry and individuality in directional sensing

Single-cell protein induction dynamics reveals a period of vulnerability to antibiotics in persister bacteria

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