Evolution of cell size control is canalized towards adders or sizers by cell cycle structure and selective pressures DOI Creative Commons
Félix Proulx-Giraldeau, Jan M. Skotheim, Paul François

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Sept. 30, 2022

Cell size is controlled to be within a specific range support physiological function. To control their size, cells use diverse mechanisms ranging from 'sizers', in which differences cell are compensated for single division cycle, 'adders', constant amount of growth occurs each cycle. This diversity raises the question why particular would implement one rather than another mechanism? address this question, we performed series simulations evolving networks. The mechanism that evolved was influenced by both cycle structure and selection pressures. Moreover, networks recapitulated known properties naturally occurring If based on G1 an S/G2/M timer, as found budding yeast some human cells, adders likely evolve. But, if phase significantly longer phase, often case mammalian vivo, sizers become more likely. Sizers also evolve when inverted so while performs control, fission S. pombe. For networks, consistently decreases until burst inhibitor drives extended much like green algae Chlamydomonas. That these such self-organized criticality shows how evolution complex systems can drive emergence critical processes.

Language: Английский

Integrating Old and New Paradigms of G1/S Control DOI Creative Commons
Seth M. Rubin, Julien Sage, Jan M. Skotheim

et al.

Molecular Cell, Journal Year: 2020, Volume and Issue: 80(2), P. 183 - 192

Published: Sept. 17, 2020

Language: Английский

Citations

210
Increasing cell size remodels the proteome and promotes senescence DOI Creative Commons
Michael C. Lanz, Evgeny Zatulovskiy, Matthew P. Swaffer

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(17), P. 3255 - 3269.e8

Published: Aug. 19, 2022

Language: Английский

Citations

144
The human cell count and size distribution DOI Creative Commons

Ian Hatton,

Eric D. Galbraith, Nono S. C. Merleau

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(39)

Published: Sept. 18, 2023

Cell size and cell count are adaptively regulated intimately linked to growth function. Yet, despite their widespread relevance, the relation between has never been formally examined over whole human body. Here, we compile a comprehensive dataset of all major types, with data drawn from >1,500 published sources. We consider body representative male (70 kg), which allows further estimates female (60 kg) 10-y-old child (32 kg). build hierarchical interface for cellular organization body, giving easy access data, methods, sources (https://humancelltreemap.mis.mpg.de/). In total, estimate total counts ≈36 trillion cells in male, ≈28 female, ≈17 child. These reveal surprising inverse count, implying trade-off these variables, such that within given logarithmic class contribute an equal fraction body's biomass. also find coefficient variation is approximately independent mean size, existence cell-size regulation across types. Our serve establish holistic quantitative framework highlight large-scale patterns biology.

Language: Английский

Citations

78
Cell size homeostasis is tightly controlled throughout the cell cycle DOI Creative Commons
Xili Liu, Jiawei Yan, Marc W. Kirschner

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(1), P. e3002453 - e3002453

Published: Jan. 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.

Language: Английский

Citations

31
Cell growth dilutes the cell cycle inhibitor Rb to trigger cell division DOI
Evgeny Zatulovskiy, Shuyuan Zhang, Daniel F. Berenson

et al.

Science, Journal Year: 2020, Volume and Issue: 369(6502), P. 466 - 471

Published: July 24, 2020

Cell size is fundamental to cell physiology. For example, determines the spatial scale of organelles and intracellular transport thereby affects biosynthesis. Although some genes that affect mammalian have been identified, molecular mechanisms through which growth drives division remained elusive. We show during G

Language: Английский

Citations

138
Eukaryotic Cell Size Control and Its Relation to Biosynthesis and Senescence DOI
Shicong Xie, Matthew P. Swaffer, Jan M. Skotheim

et al.

Annual Review of Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 38(1), P. 291 - 319

Published: May 14, 2022

The most fundamental feature of cellular form is size, which sets the scale all cell biological processes. Growth, form, and function are necessarily linked in biology, but we often do not understand underlying molecular mechanisms nor their specific functions. Here, review progress toward determining that regulate size yeast, animals, plants, as well understanding regulation. It has become increasingly clear mechanism regulation deeply intertwined with basic biosynthesis, how biosynthesis can be scaled (or not) proportion to size. Finally, highlight recent findings causally linking aberrant senescence implications for cancer therapies.

Language: Английский

Citations

69
Epithelial tissue confinement inhibits cell growth and leads to volume-reducing divisions DOI Creative Commons
John Devany,

Martin J. Falk,

Liam J. Holt

et al.

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(16), P. 1462 - 1476.e8

Published: June 19, 2023

Cell proliferation is a central process in tissue development, homeostasis, and disease, yet how regulated the context remains poorly understood. Here, we introduce quantitative framework to elucidate growth dynamics regulate cell proliferation. Using MDCK epithelial monolayers, show that limiting rate of expansion creates confinement suppresses growth; however, this does not directly affect cycle. This leads uncoupling between rates division epithelia and, thereby, reduces volume. Division becomes arrested at minimal volume, which consistent across diverse vivo. nucleus approaches minimum volume capable packaging genome. Loss cyclin D1-dependent cell-volume regulation results an abnormally high nuclear-to-cytoplasmic ratio DNA damage. Overall, demonstrate by interplay regulation.

Language: Английский

Citations

27
The bidirectional relationship between metabolism and cell cycle control DOI Creative Commons

Frances F. Diehl,

Kiera M. Sapp, Matthew G. Vander Heiden

et al.

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 34(2), P. 136 - 149

Published: June 27, 2023

Language: Английский

Citations

26
Cytosolic NADK is conditionally essential for folate-dependent nucleotide synthesis DOI
Kyle M. Flickinger,

Carlos A. Mellado Fritz,

Kimberly S. Huggler

et al.

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Language: Английский

Citations

1
Restriction point regulation at the crossroads between quiescence and cell proliferation DOI
Betheney R. Pennycook, Alexis R. Barr

FEBS Letters, Journal Year: 2020, Volume and Issue: 594(13), P. 2046 - 2060

Published: June 21, 2020

The coordination of cell proliferation with reversible cycle exit into quiescence is crucial for the development multicellular organisms and tissue homeostasis in adult. decision between occurs at restriction point, which widely thought to be located G1 phase cycle, when cells integrate accumulated extracellular intracellular signals drive this binary cellular decision. On molecular level, decision‐making exerted through activation cyclin‐dependent kinases (CDKs). CDKs phosphorylate retinoblastoma (Rb) transcriptional repressor regulate expression genes. Recently, classical view point regulation has been challenged. Here, we review latest findings on CDKs, Rb phosphorylation nature position within cycle.

Language: Английский

Citations

63