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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Polyploidy in Xenopus lowers metabolic rate by decreasing total cell surface area

Current Biology, Год журнала: 2023, Номер 33(9), С. 1744 - 1752.e7

Опубликована: Апрель 19, 2023

Although polyploidization is frequent in development, cancer, and evolution, impacts on animal metabolism are poorly understood. In Xenopus frogs, the number of genome copies (ploidy) varies across species can be manipulated within a species. Here, we show that triploid tadpoles contain fewer, larger cells than diploids consume oxygen at lower rate. Drug treatments revealed major processes accounting for tadpole energy expenditure include cell proliferation, biosynthesis, maintenance plasma membrane potential. While inhibiting proliferation did not abolish consumption difference between triploids, altered cellular biosynthesis or electrical potential did. Combining these results with simple mathematical framework, propose decrease total surface area lowered production activity components including Na

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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An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of the Drosophila wing disc

PLoS Genetics, Год журнала: 2024, Номер 20(9), С. e1011387 - e1011387

Опубликована: Сен. 3, 2024

A programmed developmental switch to G / S endocycles results in tissue growth through an increase cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute cancer. Much remains unknown, however, about how these iECs affect growth. Using the D . melanogaster wing disc as model, we find that populations of initially size then subsequently undergo a heterogenous arrest causes severe undergrowth. acquired DNA damage and activated Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant not eliminated from epithelium. Instead, entered JNK-dependent reversible senescent-like arrest. Senescent promoted division diploid neighbors, this compensatory proliferation did rescue Our study has uncovered unique attributes their effects on have important implications for understanding roles

Язык: Английский

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Plasma membrane folding enables constant surface area-to-volume ratio in growing mammalian cells

Current Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Significance of quantitative analyses of the impact of heterogeneity in mitochondrial content and shape on cell differentiation

Open Biology, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 1, 2024

Mitochondria, classically known as the powerhouse of cells, are unique double membrane-bound multifaceted organelles carrying a genome. Mitochondrial content varies between cell types and precisely doubles within cells during each proliferating cycle. also increases to variable degree differentiation triggered after exit from The mitochondrial is primarily maintained by regulation biogenesis, while damaged mitochondria eliminated mitophagy. In any with given content, steady-state number shape determined balance fission fusion processes. increase in alteration causatively linked process differentiation. Here, we critically review quantitative aspects detection methods shape. Thereafter, quantitatively link these properties differentiating highlight implications such on stem functionality. Finally, discuss an example size predicted analysis content. To significance analyses properties, propose three independent rationale based hypotheses relevant experimental designs test them.

Язык: Английский

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Premature endocycling of Drosophila follicle cells causes pleiotropic defects in oogenesis

Genetics, Год журнала: 2024, Номер 226(4)

Опубликована: Фев. 1, 2024

Abstract Endocycling cells grow and repeatedly duplicate their genome without dividing. Cells switch from mitotic cycles to endocycles in response developmental signals during the growth of specific tissues a wide range organisms. The purpose switching endocycles, however, remains unclear many tissues. Additionally, can conditional signals, which have beneficial or pathological effects on However, impact these unscheduled development is underexplored. Here, we use Drosophila ovarian somatic follicle as model examine tissue function. Follicle normally at mid-oogenesis. Inducing prematurely resulted lethality resulting embryos. Analysis ovaries with premature cell revealed aberrant follicular epithelial structure pleiotropic defects oocyte growth, gene amplification, migration special set known border cells. Overall, findings reveal how disrupt function cause development.

Язык: Английский

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An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of theDrosophilawing disc

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

Опубликована: Март 14, 2024

Summary A programmed developmental switch to G / S endocycles results in tissue growth through an increase cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute cancer. Much remains unknown, however, about how these iECs affect growth. Using the D. melanogaster wing disc as model, we find that populations of initially size then subsequently undergo a heterogenous arrest causes severe undergrowth. acquired DNA damage and activated Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant not eliminated from epithelium. Instead, entered JNK-dependent reversible senescent-like arrest. Senescent promoted division diploid neighbors, this compensatory proliferation did rescue Our study has uncovered unique attributes their effects on have important implications for understanding roles

Язык: Английский

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A switch in the mode of tissue growth extends the growth phase of Drosophila wing primordia during early pupal development

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

ABSTRACT Understanding how final organ size is established during development raises two key questions: organs increase their mass and they stop growing upon reaching an appropriate size. While growth driven by conserved signaling pathways, the mechanisms underlying arrest remain elusive. Studies on Drosophila imaginal wing discs have provided a model whereby coincides with of cell proliferation at end larval phase. Here, through 3D reconstruction volume measurements, we show that grow continuously throughout larva-to-pupa (L/P) transition proceed to later pupal period. This supplemental phase involves switch L/P uncouples from tissue growth, important contribution Insulin/IGF signaling. These findings challenge existing open new avenues for our understanding determination.

Язык: Английский

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Tetraploidy in normal tissues and diseases: mechanisms and consequences

Chromosoma, Год журнала: 2025, Номер 134(1)

Опубликована: Март 21, 2025

Abstract Tetraploidisation plays a crucial role in evolution, development, stress adaptation, and disease, but its beneficial or pathological effects different tissues remain unclear. This study aims to compare physiological unphysiological tetraploidy eight steps: 1) mechanisms of diploidy-to-tetraploidy transition, 2) induction elimination tetraploidy, 3) tetraploid cell characteristics, 4) stress-induced 5) comparison vs. 6) consequences 7) nutritional pharmacological prevention strategies tetraploidisation, 8) knowledge gaps future perspectives. Unphysiological is an adaptive response at given threshold, often involving mitotic slippage. If cells evade through apoptosis immune surveillance, they may re-enter the cycle, causing genetic instability, micronuclei formation, aneuploidy, modification epigenome development diseases. The potential contributions neurodegenerative, cardiovascular diabetes related diseases are summarized schematic figures contrasted with cancer development. responsible for transition from tolerance tetraploidisation not fully understood. Understanding these critical importance allow targeted therapies.

Язык: Английский

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