Distributed and dynamic intracellular organization of extracellular information

Granados, Alejandro A; Pietsch, Julian; Cepeda-Humerez, Sarah A.; Farquhar, Iseabail L.; Tkačik, Gašper; Swain, Peter S.

doi:10.1073/pnas.1716659115

Cited by 68 publications

(96 citation statements)

References 32 publications

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“…Analysis of 45 a single-cell channel from the Ca 2+ response in HEK293 cells stimulated with acetylcholine repetitively at various concentrations enabled the calculation of the channel capacity, which is the maximal amount of information that the channel can transfer, at 2 bits (21). This 2-bit channel capacity is higher than the 1-bit capacity calculated for cell-population channels in other studies (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). With organs, such as skeletal muscle, functioning not as a single cell, but as the sum of single cells, a multiple-cell channel should correspond to the physiological 5 communication channel.…”

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confidence: 65%

“…We established that the 10 voltages were sufficient to avoid underestimation of mutual information ( fig. S3) and that, although an overestimation bias was present, it was small enough 20 to have little effect on the calculation of the mutual information from data acquired with 20 repetitive stimulations of 551 individual myotubes ( fig. S4).…”

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confidence: 98%

“…For a cell-population channel, the mutual information relating stimulation intensity and cellular response contains only 1 bit information (Fig. 1C, left, table S1) (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), indicating that the cellular response can distinguish only the two conditions of 20 stimulation: the presence or absence of stimulation. Physiologically, cellular responses are often gradually controlled by the intensity of stimulation, meaning that a cellular response can encode more than 1 bit information.…”

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confidence: 99%

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Single-cell information analysis reveals small intra- and large intercellular variations increase cellular information capacity

Wada

Wataya

Fujii

et al. 2019

Preprint

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Cells transmit information about extracellular stimulation through signaling pathways to control cellular function. A signaling pathway can be regarded as a communication channel. In the analysis of channels of cell populations, intercellular variation is considered noise. However, intercellular variation enables individual cells to encode different information. Therefore, at the single-cell level, each cell can be regarded as an independent channel. Thus, we propose that responses of cells of the same type in tissues, such as the fibers in a skeletal muscle, should be regarded as a multiple-cell channel composed of single-cell channels, in which intercellular variation contains information. Here, we applied electrical pulses to individual myotubes from cultured C2C12 cells or dissociated skeletal muscle fibers and measured Ca2+ responses or contraction, respectively, to estimate information capacity in a biological system. For each muscle cell system, we found that a single-cell channel transmitted more information than did a cell-population channel, indicating that the cellular response is consistent with each cell (low intracellular variation) but different among individual cells (high intercellular variation). As cell number and thus the number of single-cell channels increased, a multiple-cell channel transmitted more information by incorporating the differences among individual cells. Thus, a tissue with small intracellular and large intercellular variations has the capacity to distinguish differences in stimulation intensity to precisely control physiological function.One Sentence SummarySmall intracellular and large intercellular variations increase information transmission for precise control of tissue function.

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confidence: 65%

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confidence: 98%

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confidence: 99%

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Single-cell information analysis reveals small intra- and large intercellular variations increase cellular information capacity

Wada

Wataya

Fujii

et al. 2019

Preprint

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“…To date, the only way to change crowding levels in the cells considerably and rapidly is to apply an osmotic upshift in the medium. The cell responds immediately by uptake of potassium ions to regain its volume and crowding 59 . Even in a potassium-deprived medium, the crowding effects are observed for a short period due to other response mechanisms.…”

Section: Crowding Homeostasis In Agingmentioning

confidence: 99%

A physicochemical roadmap of yeast replicative aging

Mouton

Thaller

Crane

et al. 2019

Preprint

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Author ContributionsConceptualization: S.N.M., A.J.B and L.M.V.; Investigation, Formal analysis: S.N.M. and D.J.T.; Methodology and Resources: M.M.C., I.L.R., and A.S.; Writing: S.N.M., A.J.B, and L.M.V.; Supervision: M.K., C.P.L., A.J.B, L.M.V. AbstractCellular aging is a multifactorial process that is characterized by a decline in homeostatic capacity, best described at the molecular level. Physicochemical properties such as pH and macromolecular crowding, are essential to all molecular processes in cells and require maintenance. Whether a drift in physicochemical properties contributes to the overall decline of homeostasis in aging is not known. Here we show that the cytosol of yeast cells acidifies modestly in early aging and sharply after senescence. Using a macromolecular crowding sensor optimized for long-term FRET measurements, we show the macromolecular crowding changes less in longer-lived cells in contrast to shorter-lived cells. While the average pH and crowding levels change only modestly with aging, we observe drastic changes in organellar volume, leading to crowding on the µm scale, which we term organellar crowding. Our measurements provide an initial framework of physicochemical parameters of replicatively-aged yeast cells.

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“…well environmental conditions can be discriminated based on the corresponding distributions of lifespan or gene expression. This method has been successfully applied to gene expression, biochemical activities, and physiological responses (18,22), and allows us to accommodate noisy responses and non-linear stimuli-response relationships. Using this approach (Fig.…”

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A Multicellular Network Mechanism for Temperature-Robust Food Sensing

Patel

Diana

Entchev

et al. 2019

Preprint

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Responsiveness to external cues is a hallmark of biological systems. In complex environments, organisms must remain responsive to specific inputs even as other internal or external factors fluctuate. Here we show how Caenorhabditis elegans can discriminate between food levels to modulate lifespan despite temperature perturbations. While robustness of fixed outputs has been described, our findings uncover a more complex robustness process that maintains foodresponsiveness. This end-to-end robustness from environment to physiology is mediated by foodsensing neurons that communicate via TGF-b and serotonin signals to form a multicellular gene network. Mechanistically, specific regulations in this network change with temperature to maintain similar food-responsiveness in the lifespan output. Together, our findings provide a basis for geneenvironment interactions and unveil computations that integrate environmental cues to govern physiology. Main TextRobustness is the ability of a system to maintain its performance under perturbation (1-3). It is fundamental to biological systems, enabling organisms to thrive despite fluctuations in internal processes or external environments. Mechanisms for robustness exist in many precise and stereotyped processes, such as development (1, 3), circadian rhythms (4), and rhythmic neural activity (5), to produce invariant outputs despite internal variability in signalling activities or external perturbations in environmental conditions. Unlike these stereotyped processes, much less is known about robustness in responsive processes in metazoans, where the ability to respond to one environmental cue is maintained despite fluctuations in a second factor that impact the same process. This form of robustness is 3 crucial in complex natural environments where multiple factors can fluctuate independently. A rigorous understanding of robustness necessitates explicit definition of the biological parameter that is robust, and the perturbation that it is robust to (1). Here, we investigate how discrimination between food levels is robust to temperature in the nematode C. elegans.Food and temperature affect lifespan in many species, including C. elegans (6-17). These effects can be observed when C. elegans are shifted to specific food and temperature levels during their reproductive period on day 2 of adulthood ( Fig. 1A-B; Methods) (18, 19). At 20 °C, decreasing bacterial food concentration from ad libitum to starvation leads to local maxima and minima in lifespan, which plateaus to a maximum at the lowest food levels (18) (Fig. 1C). At a baseline food level (2x10 9 bacterial cells/ml), decreasing temperature from 25 °C to 15 °C extends lifespan (Fig. 1D). Because C. elegans adopts a boom-and-bust lifestyle in temperate climates (20), these food and temperature ranges are consistent with fluctuations seen in its natural environment.To determine how these environmental factors interact, we measured lifespan under 24 combinations of food and temperature (Fig. 1B). We then stratified the results by ...

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Distributed and dynamic intracellular organization of extracellular information

Cited by 68 publications

References 32 publications

Single-cell information analysis reveals small intra- and large intercellular variations increase cellular information capacity

Single-cell information analysis reveals small intra- and large intercellular variations increase cellular information capacity

A physicochemical roadmap of yeast replicative aging

A Multicellular Network Mechanism for Temperature-Robust Food Sensing

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