Gravity sensing in plant and animal cells

Takahashi, Ken; Takahashi, Hideyuki; Furuichi, Teiichi; Toyota, Masatsugu; Furutani-Seiki, Makoto; Kobayashi, Takashi; Watanabe-Takano, Haruko; Shirakawa, Masahiro; Numaga‐Tomita, Takuro; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Naruse, Keiji

doi:10.1038/s41526-020-00130-8

Cited by 45 publications

(21 citation statements)

References 109 publications

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“…In plant biology, gravity sensing has a rich history, due to the fact that plants exhibit gravitropism, which has been known for over a century. As such, mechanisms for gravity response by plants and plant cells are fairly well established [ 13 , 14 , 15 , 16 ]. For example, the gravity-dependent sedimentation of statoliths and auxin (a plant growth hormone) is well-known.…”

Section: Introductionmentioning

confidence: 99%

Adaptation and Changes in Actin Dynamics and Cell Motility as Early Responses of Cultured Mammalian Cells to Altered Gravitational Vector

Zhang

Thomas

Chiu

et al. 2022

IJMS

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Cultured mammalian cells have been shown to respond to microgravity (μG), but the molecular mechanism is still unknown. The study we report here is focused on molecular and cellular events that occur within a short period of time, which may be related to gravity sensing by cells. Our assumption is that the gravity-sensing mechanism is activated as soon as cells are exposed to any new gravitational environment. To study the molecular events, we exposed cells to simulated μG (SμG) for 15 min, 30 min, 1 h, 2 h, 4 h, and 8 h using a three-dimensional clinostat and made cell lysates, which were then analyzed by reverse phase protein arrays (RPPAs) using a panel of 453 different antibodies. By comparing the RPPA data from cells cultured at 1G with those of cells under SμG, we identified a total of 35 proteomic changes in the SμG samples and found that 20 of these changes took place, mostly transiently, within 30 min. In the 4 h and 8 h samples, there were only two RPPA changes, suggesting that the physiology of these cells is practically indistinguishable from that of cells cultured at 1G. Among the proteins involved in the early proteomic changes were those that regulate cell motility and cytoskeletal organization. To see whether changes in gravitational environment indeed activate cell motility, we flipped the culture dish upside down (directional change in gravity vector) and studied cell migration and actin cytoskeletal organization. We found that compared with cells grown right-side up, upside-down cells transiently lost stress fibers and rapidly developed lamellipodia, which was supported by increased activity of Ras-related C3 botulinum toxin substrate 1 (Rac1). The upside-down cells also increased their migratory activity. It is possible that these early molecular and cellular events play roles in gravity sensing by mammalian cells. Our study also indicated that these early responses are transient, suggesting that cells appear to adapt physiologically to a new gravitational environment.

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Section: Introductionmentioning

confidence: 99%

Adaptation and Changes in Actin Dynamics and Cell Motility as Early Responses of Cultured Mammalian Cells to Altered Gravitational Vector

Zhang

Thomas

Chiu

et al. 2022

IJMS

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“…Based on these initial observations on the morphometric characteristics of these tubules forming in constructs, long-term studies could search for differences in the number of projections and their comparative lengths. This could provide further answers regarding the differences in the bone remodelling process between simulated microgravity and the normal context, especially in cytoskeletal organisation, which has been reported to change in microgravity 97 , 98 .…”

Section: Resultsmentioning

confidence: 88%

Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration

et al. 2021

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Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular component located within. This manuscript presents the development of a micron-scale bone organoid prototype, a concept that can allow the study of bone processes at the cell-tissue interface. The model is constructed with a combination of primary female osteoblastic and osteoclastic cells, seeded onto femoral head micro-trabeculae, where they recapitulate relevant phenotypes and functions. Subsequently, constructs are inserted into a simulated microgravity bioreactor (NASA-Synthecon) to model a pathological state of reduced mechanical stimulation. In these constructs, we detected osteoclastic bone resorption sites, which were different in morphology in the simulated microgravity group compared to static controls. Once encapsulated in human fibrin and exposed to analogue microgravity for 5 days, masses of bone can be observed being lost from the initial structure, allowing to simulate the bone loss process further. Constructs can function as multicellular, organotypic units. Large osteocytic projections and tubular structures develop from the initial construct into the matrix at the millimetre scale. Micron-level fragments from the initial bone structure are detected travelling along these tubules and carried to sites distant from the native structure, where new matrix formation is initiated. We believe this model allows the study of fine-level physiological processes, which can shed light into pathological bone loss and imbalances in bone remodelling.

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“…While there are several hypotheses for gravity sensing mechanisms, epigenetic triggers, and potential feedback loops in mammalian cells, that exacerbate inhibition over time 66 , the dependence of these mechanisms across a range of simulated gravities has not yet been elucidated and warrants further investigation in future spaceflights to Moon and Mars. In the meantime, a reasonable validation of these results, and other partial-gravity simulations on Earth, could also be done in orbital microgravity on the ISS, using a variable counterweight centrifuge 42 .…”

Section: Discussionmentioning

confidence: 99%

Impairment of 7F2 osteoblast function by simulated partial gravity in a Random Positioning Machine

Braveboy-Wagner

Lelkes

2022

npj Microgravity

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The multifaceted adverse effects of reduced gravity pose a significant challenge to human spaceflight. Previous studies have shown that bone formation by osteoblasts decreases under microgravity conditions, both real and simulated. However, the effects of partial gravity on osteoblasts’ function are less well understood. Utilizing the software-driven newer version of the Random Positioning Machine (RPMSW), we simulated levels of partial gravity relevant to future manned space missions: Mars (0.38 G), Moon (0.16 G), and microgravity (Micro, ~10−3 G). Short-term (6 days) culture yielded a dose-dependent reduction in proliferation and the enzymatic activity of alkaline phosphatase (ALP), while long-term studies (21 days) showed a distinct dose-dependent inhibition of mineralization. By contrast, expression levels of key osteogenic genes (Alkaline phosphatase, Runt-related Transcription Factor 2, Sparc/osteonectin) exhibited a threshold behavior: gene expression was significantly inhibited when the cells were exposed to Mars-simulating partial gravity, and this was not reduced further when the cells were cultured under simulated Moon or microgravity conditions. Our data suggest that impairment of cell function with decreasing simulated gravity levels is graded and that the threshold profile observed for reduced gene expression is distinct from the dose dependence observed for cell proliferation, ALP activity, and mineral deposition. Our study is of relevance, given the dearth of research into the effects of Lunar and Martian gravity for forthcoming space exploration.

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Gravity sensing in plant and animal cells

Cited by 45 publications

References 109 publications

Adaptation and Changes in Actin Dynamics and Cell Motility as Early Responses of Cultured Mammalian Cells to Altered Gravitational Vector

Adaptation and Changes in Actin Dynamics and Cell Motility as Early Responses of Cultured Mammalian Cells to Altered Gravitational Vector

Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration

Impairment of 7F2 osteoblast function by simulated partial gravity in a Random Positioning Machine

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