Cell-cycle-linked growth reprogramming encodes developmental time into leaf morphogenesis

Current Biology, Год журнала: 2024, Номер 34(3), С. 541 - 556.e15

Опубликована: Янв. 21, 2024

How is time encoded into organ growth and morphogenesis? We address this question by investigating heteroblasty, where leaf development form are modified with progressing plant age. By combining morphometric analyses, fate-mapping through live-imaging, computational genetics, we identify age-dependent changes in cell-cycle-associated histogenesis that underpin heteroblasty. show juvenile leaves, cell proliferation competence rapidly released a "proliferation burst" coupled fast growth, whereas adult proliferative sustained for longer at slower rate. These effects mediated the SPL9 transcription factor response to inputs from both shoot age individual maturation along proximodistal axis. acts activating CyclinD3 family genes, which sufficient bypass requirement control of shape heteroblastic reprogramming cellular growth. In conclusion, have identified mechanism bridges across cell, tissue, whole-organism scales linking geometry.

Язык: Английский

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Mechanical control of cell proliferation patterns in growing epithelial monolayers

Biophysical Journal, Год журнала: 2024, Номер 123(7), С. 909 - 919

Опубликована: Март 6, 2024

Язык: Английский

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Stem cell mechanoadaptation. I. Effect of microtubule stabilization and volume changing stresses on cytoskeletal remodeling

APL Bioengineering, Год журнала: 2025, Номер 9(1)

Опубликована: Янв. 7, 2025

Here, we report on the first part of a two-part experimental series to elucidate spatiotemporal cytoskeletal remodeling, which underpins evolution stem cell shape and fate, emergence tissue structure function. In Part I these studies, develop protocols stabilize microtubules exogenously using paclitaxel (PAX) in standardized model murine embryonic line (C3H/10T1/2) maximize comparability with previously published studies. We then probe native microtubule-stabilized cells' capacity adapt volume changing stresses effected by seeding at increasing densities, emulates local compression template formation during development. Within concentration range 1–100 nM, cells maintain viability reduce proliferation. PAX stabilization is associated increased as well flattening nucleus. Compared control cells, exhibit thick, bundled highly aligned, thicker longer F-actin fibers, corresponding an increase Young's modulus cell. Both microtubule concentration, whereby more prominent basal region The observed globally across apical Seeding target densities induces cells. This modulates concomitant increases greater degree than via PAX. Cells seeded high density higher bulk low density. These data demonstrate interplay mechanical chemical cues, i.e., respective exogenous stabilization; resulting remodeling manifests properties relevant development multicellular constructs.

Язык: Английский

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The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2135 - 2135

Опубликована: Фев. 10, 2024

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing formation cancerous tissues. CI can be further categorized into two distinct yet interrelated components: locomotion (CIL) and proliferation (CIP). These components have historically been viewed as separate processes, but emerging research suggests that they may regulated by both shared pathways. Specifically, recent studies indicated CIP CIL utilize mechanotransduction pathways, process involves cells sensing responding to mechanical forces. This review article describes role in CI, shedding light on how forces regulate CIP. Emphasis is placed filamin A (FLNA)-mediated mechanotransduction, elucidating FLNA senses translates them biochemical signals cell proliferation. In addition FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable directly indirectly binding specific DNA sequences distant genes gene expression, emerge sensitive players signaling pathways CI. presents methods identifying these TAF profiling associated changes chromatin structure, offering valuable insights other biological functions mediated mechanotransduction. Finally, it addresses unanswered questions fields delineates their possible future directions.

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 mechanical influence of densification on epithelial architecture

PLoS Computational Biology, Год журнала: 2024, Номер 20(4), С. e1012001 - e1012001

Опубликована: Апрель 1, 2024

Epithelial tissues are the most abundant tissue type in animals, lining body cavities and generating compartment barriers. The function of a monolayered epithelial tissue–whether protective, secretory, absorptive, or filtrative–relies on side-by-side arrangement its component cells. mechanical parameters that determine shape cells apical-basal plane not well-understood. architecture culture is intimately connected to cell density, cultured layers transition between architectures as they proliferate. This prompted us ask what extent emerges from two considerations: A) constraints densification B) cell-cell adhesion, hallmark feature To address these questions, we developed novel polyline cell-based computational model used it make theoretical predictions about upon changes density adhesion. We tested using experiments. Our results show appearance extended lateral borders arises consequence crowding–independent However, cadherin-mediated adhesion associated with architectural transition. suggest this represents initial distinctive architecture. Together our work reveals distinct roles layer formation provides framework understand less well-studied tissues.

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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Capturing the mechanosensitivity of cell proliferation in models of epithelium

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(45)

Опубликована: Окт. 28, 2024

Despite the primary role of cell proliferation in tissue development and homeostatic maintenance, interplay between density, mechanoresponse, growth division is not yet understood. In this article, we address issue by reporting on an experimental investigation all time- length-scales a model tissue, grown collagen-coated glass or deformable substrates. Through extensive data analysis, demonstrate relation mechanoresponse probability for division, as function local density. Motivated these results, construct minimal environment that can recover data. By parameterizing dividing phases cycle, introducing such dissipative particle dynamics simulations, mechanoresponsive, time-dependent density profiles 2D tissues growing to macroscopic scales. The importance separating population into cells, each characterized particular time scale, further emphasized calculations based adapted Fisher–Kolmogorov equations. Together, results show level constitutive its matrix-sensitive active pressure. latter evokes massive cooperative displacement cells invading key factor developing large-scale structures steady state.

Язык: Английский

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Same same but different? How blood and lymphatic vessels induce cell contact inhibition

Biochemical Society Transactions, Год журнала: 2025, Номер 53(01)

Опубликована: Фев. 6, 2025

Endothelial cells (ECs) migrate, sprout, and proliferate in response to (lymph)angiogenic mitogens, such as vascular endothelial growth factors. When ECs reach high confluency encounter spatial confinement, they establish mature cell–cell junctions, reduce proliferation, enter a quiescent state through process known contact inhibition. However, EC quiescence is modulated not only by confinement but also other mechano-environmental factors, including blood or lymph flow extracellular matrix properties. Changes physical forces intracellular signaling can disrupt inhibition, resulting aberrant proliferation dysfunction. Therefore, it critical understand the mechanisms which regulate While inhibition has been well studied (BECs), its regulation lymphatic (LECs) remains largely unexplored. Here, we review current knowledge on extrinsic stimuli intrinsic molecular pathways that govern highlight nuanced differences between BECs LECs. Furthermore, provide perspectives for future research A deeper understanding of BEC LEC-specific underlying may enable targeted modulation this vessels with relevance vascular-specific disorders.

Язык: Английский

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Spatial confinement and life under pressure from physiology to pathology

npj Biological Physics and Mechanics., Год журнала: 2025, Номер 2(1)

Опубликована: Март 5, 2025

Язык: Английский

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