Learning developmental mode dynamics from single-cell trajectories
Nicolas Romeo, Alasdair Hastewell, Alexander Mietke, Jörn Dunkel
备注：
Active Brownian particle data and analysis added, inference framework improved, 8 figures and 1 Appendix added, Main text and appendices extended main text: 19 pages, 4 main figures, 6 figure supplements; Appendix: 15 pages, 8 figures
Embryogenesis is a multiscale process during which developmental symmetry breaking transitions give rise to complex multicellular organisms. Recent advances in high-resolution live-cell microscopy provide unprecedented insights into the collective cell dynamics at various stages of embryonic development. This rapid experimental progress poses the theoretical challenge of translating high-dimensional imaging data into predictive low-dimensional models that capture the essential ordering principles governing developmental cell migration in complex geometries. Here, we combine mode decomposition ideas that have proved successful in condensed matter physics and turbulence theory with recent advances in sparse dynamical systems inference to realize a computational framework for learning quantitative continuum models from single-cell imaging data. Considering pan-embryo cell migration during early gastrulation in zebrafish as a widely studied example, we show how cell trajectory data on a curved surface can be coarse-grained and compressed with suitable harmonic basis functions. The resulting low-dimensional representation of the collective cell dynamics enables a compact characterization of developmental symmetry breaking and the direct inference of an interpretable hydrodynamic model, which reveals similarities between pan-embryo cell migration and active Brownian particle dynamics on curved surfaces. Due to its generic conceptual foundation, we expect that mode-based model learning can help advance the quantitative biophysical understanding of a wide range of developmental structure formation processes.
Rapid advance of experimental techniques provides an unprecedented in-depth view into complex developmental processes. Still, little is known on how the complexity of multicellular organisms evolved by elaborating developmental programs and inventing new cell types. A hurdle to understanding developmental evolution is the difficulty of even describing the intertwined network of spatiotemporal processes underlying the development of complex multicellular organisms. Nonetheless, an overview of developmental trajectories can be obtained from cell type lineage maps. Here, we propose that these lin…
A hyperbolic cell cycle law for early embryonic developmental timing
University of Graz（格拉茨大学）；European Molecular Biology Laboratory（欧洲分子生物学实验室）；Heidelberg University（海德堡大学）；École normale supérieure, Université PSL（巴黎高等师范学院，巴黎文理研究大学）；Sorbonne Université（索邦大学）；Université Paris Cité（巴黎西岱大学）；INSERM（法国国家健康与医学研究院）
Deformations of cell sheets during morphogenesis are driven by developmental processes such as cell division and cell shape changes. In morphoelastic shell theories of development, these processes appear as variations of the intrinsic geometry of a thin elastic shell. However, morphogenesis often involves large bending deformations that are outside the formal range of validity of these shell theories. Here, by asymptotic expansion of three-dimensional incompressible morphoelasticity in the limit of a thin shell, we derive a shell theory for large intrinsic bending deformations and emphasise th…
The development of multicellular organisms proceeds through a series of morphogenetic and cell-state transitions, transforming homogeneous zygotes into complex adults by a process of self-organization. Many of these transitions are achieved by spontaneous symmetry breaking mechanisms, allowing cells and tissues to acquire pattern and polarity by virtue of local interactions without an upstream supply of information. The combined work of theory and experiment has elucidated how these systems break symmetry during developmental transitions. Given such transitions are multiple and their temporal …
Tissue engineering technology and tissue cell-based stem cell research have made great strides in treating tissue and organ damage, correcting tissue and organ dysfunction, and reducing surgical complications. In the past, traditional methods have used biological substitutes for tissue repair materials, while tissue engineering technology has focused on merging sperm cells with biological materials to form biological tissues with the same structure and function as their own tissues. The advantage is that tissue engineering technology can overcome donors. Material procurement restrictions can e…
The bacterium Myxoccocus xanthus produces multicellular protective droplets called fruiting bodies when starved. These structures form initially through the active dewetting of cells into surface-bound droplets, where substantial flows of the material are needed as the fruiting bodies grow and become round. These dynamics are followed by a primitive developmental process in which the fluid-like droplets of motile cells mature into mechanically-resilient mounds of non-motile spores that can resist significant mechanical perturbation from the external environment. To date, the mechanical propert…
Collective cell migration plays a central role in tissue development, morphogenesis, wound repair and cancer progression. With the growing realization that physical forces mediate cell motility in development and physiology, a key biological question is how cells integrate molecular activities for force generation on multicellular scales. In this review we discuss recent advances in modeling collective cell migration using quantitative tools and approaches rooted in soft matter physics. We focus on theoretical models of cell aggregates as continuous active media, where the feedback between mec…
Non-Markovian non-equilibrium modeling of experimental cell-motion trajectories reveals dependence of propulsion-force correlations on solvent viscosity
Freie Universität Berlin（柏林自由大学）；Indian Institute of Science（印度科学学院）
California Institute of Technology（加州理工学院）；University of Cambridge（剑桥大学）；Harvard Medical School（哈佛医学院）；Washington University School of Medicine（华盛顿大学医学院）
Polarization of the mammalian embryo at the right developmental time is critical for its development to term and would be valuable in assessing the potential of human embryos. However, tracking polarization requires invasive fluorescence staining, impermissible in the in vitro fertilization clinic. Here, we report the use of artificial intelligence to detect polarization from unstained time-lapse movies of mouse embryos. We assembled a dataset of bright-field movie frames from 8-cell-stage embryos, side-by-side with corresponding images of fluorescent markers of cell polarization. We then used…
A statistical analysis of particle trajectories in living cells
分子生物学和荧光显微镜成像的最新进展使活细胞中单分子动力学的推断成为可能。这种推断允许确定细胞的组织和功能。用跟踪算法计算的细胞中颗粒的轨迹可以用扩散过程建模。三种类型的扩散被认为是：（i）自由扩散;（ii）subdiffusion或（iii）superdiffusion。均方位移（MSD）通常用于确定活细胞中颗粒的不同类型的动力学（Qian，Sheetz和Elson 1991）。在这里，我们提出了一个非参数的三决策测试作为替代的MSD方法。对原假设--自由扩散--的拒绝伴随着对替代方向（亚扩散或超扩散）的主张。例如，我们研究了在原假设下以及在生物物理学文献中目前考虑的参数替代方案下（Monnier et al，2012）检验统计量的渐近行为。此外，我们调整Benjamini和Hochberg（2000）的程序，以适应三决策测试设置，以便将测试程序应用于独立轨迹的集合。通过蒙特卡罗实验证实了该方法的性能优于MSD方法。该方法被证明对应于在荧光显微镜观察到的蛋白质动力学的真实数据集。
The flexibility of the bacterial flagellar hook is believed to have substantial consequences for microorganism locomotion. Using a simplified model of a rigid flagellum and a flexible hook, we show that the paths of axisymmetric cell bodies driven by a single flagellum in Stokes flow are generically helical. Phase-averaged resistance and mobility tensors are produced to describe the flagellar hydrodynamics, and a helical rod model which retains a coupling between translation and rotation is identified as a distinguished asymptotic limit. A supercritical Hopf bifurcation in the flagellar orient…
