Virtual-tissue computer simulations define the roles of cell adhesion and proliferation in the onset of kidney cystic disease

Belmonte, Julio M.; Clendenon, Sherry G.; Oliveira, Guilherme Monteiro; Swat, Maciej; Greene, Evan V.; Srividhya, Jeyaraman; Glazier, James A.; Bacallao, Robert L.

doi:10.1091/mbc.e16-01-0059

Cited by 44 publications

(45 citation statements)

References 67 publications

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“…In order to test the mechanism of fibroblast behaviour and spatial organisation during dermal maturation, we developed a 3D model in Compucell3D (Belmonte et al, 2016;Hirashima et al, 2017;Swat et al, 2012). We conceptualized the whole animal as a cylindrical object and focused on modelling the dermis between neighbouring hair follicles, to avoid considering changes in the skin associated with the hair growth cycle (Donati et al, 2014).…”

Section: A 3d Tissue Model Recapitulates Dermal Maturationmentioning

confidence: 99%

“…Hogeweg/Cellular Potts Model (GGH/CPM) represents a single cell as an extended domain of sites (pixels) on a regular lattice that share a common index σ. For detailed information about GGH/CPM see (Belmonte et al, 2016;Swat et al, 2012). In brief, a cellular Potts model was implemented using the CompuCell3D platform (Swat et al, 2012).…”

Section: Tissue Model: Glazier Graner Hogeweg/cellular Potts Simulatimentioning

confidence: 99%

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Fibroblast state switching orchestrates dermal maturation and wound healing

Rognoni

Pisco

Hiratsuka

et al. 2017

Preprint

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SummaryMurine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here we propose a mathematical model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Our model faithfully recapitulates dermal maturation, predicting a loss of spatial segregation of fibroblast lineages and dictating that fibroblast migration is only required for wound healing. To test this we performed in vivo live imaging of dermal fibroblasts, which revealed that homeostatic tissue architecture is achieved without active cell migration. In contrast, both fibroblast proliferation and migration are key determinants of tissue repair following wounding. The results show that tissue-scale coordination is driven by the interdependence of cell proliferation and ECM deposition, paving the way for identifying new therapeutic strategies to enhance skin regeneration.

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Section: A 3d Tissue Model Recapitulates Dermal Maturationmentioning

confidence: 99%

Section: Tissue Model: Glazier Graner Hogeweg/cellular Potts Simulatimentioning

confidence: 99%

Fibroblast state switching orchestrates dermal maturation and wound healing

Rognoni

Pisco

Hiratsuka

et al. 2017

Preprint

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“…Additionally, such a computational framework could both facilitate design of novel tissues of potential biomedical interest and delineate which structures might or might not be possible (Elowitz and Lim, 2010;Ollé-Vila et al, 2016). Our work takes inspiration from the many examples of computational models developed and successfully used to replicate various natural developmental processes (Belmonte et al, 2016;Hester et al, 2011;Hutson et al, 2017;Lakatos et al, 2018;Lambert et al, 2018;Lin et al, 2009;Marin-Riera et al, 2018;Shaya et al, 2017;Swat et al, 2015), and brings them into the constructive viewpoint of design instead of understanding.…”

mentioning

confidence: 99%

A parametrized computational framework for description and design of genetic circuits of morphogenesis based on contact-dependent signaling and changes in cell-cell adhesion

Morsut¹,

Lam²

2019

Preprint

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Synthetic development is a nascent field of research that uses the tools of synthetic biology to design genetic programs directing cellular patterning and morphogenesis in higher eukaryotic cells, such as mammalian cells. Synthetic genetic networks comprising cell-cell communications and morphogenesis effectors (e.g. adhesion) are generated and integrated into a cellular genome. Current design methods for these genetic programs rely on trial and error, which limit the number of possible circuits and parameter ranges that can be explored. By contrast, computational models act as rapid testing platforms, revealing the networks, signals, and responses required for achieving robust target structures. Here we introduce a computational framework, based on cellular Potts, where contact dependent cell-cell signaling networks and cellular responses can be chosen in a modular fashion. We represent and tune a number of recently described synthetic morphogenic trajectories in silico, such as those resulting in multilayered synthetic spheroids. Our parameters were tuned using a comparison with published in vitro experimental results. Our tuned parameters were then used to design and explore novel developmental trajectories for the formation of elongated and oscillatory structures. Here, multiple rounds of optimization suggested critical parameters for the successful implementation of these trajectories. The framework that we develop here could function as a testing ground to explore how synthetic biology tools can be used to create particular multicellular trajectories, as well as for understanding both imagined and extant developmental trajectories.

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“…It provides a set of PDE solvers that operate at tissue and organ scale while the reaction-kinetics solvers that CC3D provides (implemented using libroarrunner [15]) allow modeling of intracellularphenomena. By appropriate linking the modeling scales (from molecular to organ-level), we can build very sophisticated models of tissues and thus gain insight into how disease processes in tissues originate and progress [16][17] [18]. CC3D implements CPM [13] also known as Glazier-Graner-Hogeweg Model (GGH) [19][20] [21] [22].…”

Section: Compucell3dmentioning

confidence: 99%

Development of a Coupled Simulation Toolkit for Computational Radiation Biology Based on Geant4 and CompuCell3D

Liu

Higley

Swat

et al. 2020

Preprint

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Understanding and designing clinical radiation therapy is one of the most important areas of state-ofthe-art oncological treatment regimens. Decades of research have gone into developing sophisticated treatment devices and optimization protocols for schedules and dosages. In this paper, we presented a comprehensive computational platform that facilitates building of the sophisticated multi-cell-based model of how radiation affects the biology of living tissue. We designed and implemented a coupled simulation method, including a radiation transport model, and a cell biology model, to simulate the tumor response after irradiation. The radiation transport simulation was implemented through Geant4which is an open-source Monte Carlo simulation platform that provides many flexibilities for users, as well as low energy DNA damage simulation physics, Geant4-DNA. The cell biology simulation was implemented using CompuCell3D (CC3D) which is a cell biology simulation platform. In order to couple Geant4 solver with CC3D, we developed a "bridging" module that extracts tumor cellular geometry of the CC3D simulation (including specification of the individual cells) and ported it to the Geant4 for radiation transport simulation. The cell dose and cell DNA damage distribution in multicellular system were obtained using Geant4. The tumor response was simulated using cell-based tissue models based on CC3D. By merging two powerful and widely used modeling platforms, CC3D and Geant4, we delivered a novel tool that can give us the ability to simulate the dynamics of biological tissue in the presence of ionizing radiation, which provides a powerful framework for quantifying the biological consequences of radiation therapy. The developed tool has an advantage on that it has strong extensibility due to the exploitability of two modeling platforms. In this introductory methods paper, we described our modeling platform in detail and showed how it can be applied to study the application of radiotherapy to a vascularized tumor.

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Virtual-tissue computer simulations define the roles of cell adhesion and proliferation in the onset of kidney cystic disease

Cited by 44 publications

References 67 publications

Fibroblast state switching orchestrates dermal maturation and wound healing

Fibroblast state switching orchestrates dermal maturation and wound healing

A parametrized computational framework for description and design of genetic circuits of morphogenesis based on contact-dependent signaling and changes in cell-cell adhesion

Development of a Coupled Simulation Toolkit for Computational Radiation Biology Based on Geant4 and CompuCell3D

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