Cell size homeostasis is tightly controlled throughout the cell cycle

PLoS Biology, Год журнала: 2024, Номер 22(1), С. e3002453 - e3002453

Опубликована: Янв. 5, 2024

To achieve a stable size distribution over multiple generations, proliferating cells require means of counteracting stochastic noise in the rate growth, time spent various phases cell cycle, and imprecision placement plane division. In most widely accepted model, is thought to be regulated at G1/S transition, such that smaller than critical pause end G1 phase until they have accumulated mass predetermined threshold, which point proceed through rest cycle. However, based solely on specific checkpoint G1/S, cannot readily explain why with deficient control mechanisms are still able maintain very distribution. Furthermore, model would not easily account for variation during subsequent anticipated G1/S. address questions, we applied computationally enhanced quantitative microscopy (ceQPM) populations cultured human lines, enables highly accurate measurement dry individual throughout From these measurements, evaluated factors contribute maintaining homeostasis any Our findings reveal accurately maintained, despite disruptions normal machinery or perturbations growth. Control generally confined regulation length. Instead imposed lines examined, find coefficient (CV) population begins decline well before transition continues S G2 phases. Among different types tested, detailed response growth differs. general, when it falls below exponential natural increase CV effectively constrained. We both mass-dependent cycle modulation reducing within population. Through interplay coordination 2 processes, emerges. Such previously unappreciated general principles cells. These same regulatory processes might also operative terminally differentiated Further dynamical studies should lead better understanding underlying molecular control.

Язык: Английский

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Eukaryotic cell size regulation and its implications for cellular function and dysfunction

Physiological Reviews, Год журнала: 2024, Номер 104(4), С. 1679 - 1717

Опубликована: Июнь 20, 2024

Depending on cell type, environmental inputs, and disease, the cells in human body can have widely different sizes. In recent years, it has become clear that size is a major regulator of function. However, we are only beginning to understand how optimization function determines given cell’s optimal size. Here, review currently known control strategies eukaryotic intricate link intracellular biomolecular scaling, organelle homeostasis, cycle progression. We detail size-dependent regulation early development impact differentiation. Given importance for normal cellular physiology, must account changing conditions. describe sense stimuli, such as nutrient availability, accordingly adapt their by regulating growth Moreover, discuss correlation pathological states with misregulation long time this was considered downstream consequence dysfunction. newer studies reveal reversed causality, misregulated leading pathophysiological phenotypes senescence aging. summary, highlight important roles dysfunction, which could implications both diagnostics treatment clinic.

Язык: Английский

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The G1/S transition in mammalian stem cellsin vivois autonomously regulated by cell size

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 11, 2024

Cell growth and division must be coordinated to maintain a stable cell size, but how this coordination is implemented in multicellular tissues remains unclear. In unicellular eukaryotes, autonomous size control mechanisms couple with little extracellular input. However, we do not know if operate the same way or whether cycle progression are separately controlled by cell-extrinsic signals. Here, address question tracking single epidermal stem cells growing adult mice. We find that cell-autonomous mechanism, dependent on RB pathway, sets timing of S phase entry based cell's current size. Cell-extrinsic variations cellular microenvironment affect rates coupling. Our work reassesses long-standing models regulation within complex metazoan identifies as critical mechanism regulating divisions

Язык: Английский

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Systemic orchestration of cell size throughout the body: influence of sex and rapamycin exposure in Drosophila melanogaster

Biology Letters, Год журнала: 2023, Номер 19(3)

Опубликована: Март 1, 2023

Along with differences in life histories, metazoans have also evolved vast cellularity, involving changes the molecular pathways controlling cell cycle. The extent to which signalling network systemically determines cellular composition throughout body and whether tissue cellularity is organized locally match tissue-specific functions are unclear. We cultured genetic lines of Drosophila melanogaster on food without rapamycin manipulate activity target (TOR)/insulin evaluate cell-size five types adult cells: wing leg epidermal cells, ommatidial indirect flight muscle cells Malpighian tubule epithelial cells. Rapamycin blocks TOR multiprotein complex 1, reducing growth, but this effect has been studied single types. As adults, rapamycin-treated flies had smaller bodies consistently all tissues. Regardless, females eclosed larger tissues than males. Thus, sex were associated orchestration size body, leading size. postulate that TOR/insulin their effects should be considered when investigating origin ecological evolutionary patterns histories.

Язык: Английский

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The Role of Intracellular Potassium in Cell Quiescence, Proliferation, and Death

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 884 - 884

Опубликована: Янв. 10, 2024

This brief review explores the role of intracellular K+ during transition cells from quiescence to proliferation and induction apoptosis. We focus on relationship between growth rates different cells, including transformed in culture as well human quiescent T mesenchymal stem analyze concomitant changes water content both proliferating apoptotic cells. Evidence is discussed indicating that initiation cell apoptosis occur parallel with therefore do not lead significant concentration. conclude K+, a dominant ion, involved regulation volume transit quiescence, dividing higher than or differentiated which can be considered hallmark transformation.

Язык: Английский

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Rapamycin supplementation ofDrosophila melanogasterlarvae results in less viable adults with smaller cells

Royal Society Open Science, Год журнала: 2023, Номер 10(6)

Опубликована: Июнь 1, 2023

The intrinsic sources of mortality relate to the ability meet metabolic demands tissue maintenance and repair, ultimately shaping ageing patterns. Anti-ageing mechanisms compete for resources with other functions, including those involved in maintaining functional plasma membranes. Consequently, organisms smaller cells more membranes should devote membrane maintenance, leading accelerated ageing. To investigate this unexplored trade-off, we reared Drosophila melanogaster larvae on food or without rapamycin (a TOR pathway inhibitor) produce small- large-celled adult flies, respectively, measured their rates. Males showed higher than females. As expected, small-celled flies (rapamycin) counterparts (control), but only early adulthood. Contrary predictions, median lifespan was similar between groups. Rapamycin administered adults prolongs life; thus, known direct physiological effects cannot explain our results. Instead, invoke indirect rapamycin, manifested as reduced cell size, a driver increased mortality. We conclude that size differences associated burdens costs may be important overlooked factors influencing patterns nature.

Язык: Английский

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RUCova: Removal of Unwanted Covariance in mass cytometry data

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 28, 2024

High dimensional mass cytometry is confounded by unwanted covariance due to variations in cell size and staining efficiency, making analysis interpretation challenging. We present RUCova, a novel method designed address confounding factors data. RUCova removes using multivariate linear regression on Surrogates of Unwanted Covariance (SUCs), Principal Component Analysis (PCA). exemplify the use show that it effectively while preserving genuine biological signals. Our results demonstrate efficacy elucidating complex data patterns, facilitating identification activated signalling pathways, improving classification important populations. By providing robust framework for normalization interpretation, enhances accuracy reliability analyses, contributing advancements our understanding cellular biology disease mechanisms. The R package available https://github.com/molsysbio/RUCova . Detailed documentation, data, code required reproduce are https://doi.org/10.5281/zenodo.10913464 Supplementary material: Available at bioRxiv.

Язык: Английский

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Mechanochemical control systems regulating animal cell size

Current Opinion in Cell Biology, Год журнала: 2024, Номер 91, С. 102443 - 102443

Опубликована: Ноя. 6, 2024

Язык: Английский

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The fate of pyruvate dictates cell growth by modulating cellular redox potential

Опубликована: Дек. 30, 2024

Pyruvate occupies a central node in carbohydrate metabolism such that how it is produced and consumed can optimize cell for energy production or biosynthetic capacity. This has been primarily studied proliferating cells, but observations from the post-mitotic Drosophila fat body led us to hypothesize pyruvate fate might dictate rapid growth observed this organ during development. Indeed, we demonstrate augmented mitochondrial import prevented cells vivo as well cultured mammalian hepatocytes human hepatocyte-derived vitro . effect on size was caused by an increase NADH/NAD + ratio, which rewired toward gluconeogenesis suppressed biomass-supporting glycolytic pathway. Amino acid synthesis decreased, resulting loss of protein growth. Surprisingly, all occurred face activated pro-growth signaling pathways, including mTORC1, Myc, PI3K/Akt. These highlight evolutionarily conserved role setting balance between extraction biomass specialized cells.

Язык: Английский

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Oxygen and temperature affect cell sizes differently among tissues and between sexes of Drosophila melanogaster

Journal of Insect Physiology, Год журнала: 2023, Номер 150, С. 104559 - 104559

Опубликована: Авг. 26, 2023

Spatio-temporal gradients in thermal and oxygen conditions trigger evolutionary developmental responses ectotherms' body size cell size, which are commonly interpreted as adaptive. However, the evidence for cell-size is fragmentary, typically assessed single tissues. In a laboratory experiment, we raised genotypes of Drosophila melanogaster at all combinations two temperatures (16 °C or 25 °C) levels (10% 22%) measured sizes cells different For each sex, epidermal wing leg ommatidial an eye. males, also epithelial Malpighian tubule muscle flight muscle. On average, females emerged larger than did having Flies either sex smaller when under warm hypoxic conditions. Development resulted most hypoxia some tissues, especially among females. Altogether, our results show shifts adult coupled with systemic orchestration throughout fly. The nature these patterns supports model ectotherm adjusts its life-history traits cellular composition to prevent severe level. revealed inconsistencies linked type, environmental parameters, suggest caution translating information obtained type organism whole.

Язык: Английский

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