CDEV Subgroup Contributed Talks

Flavia Feliciangeli

University of Leeds, Bayer AG

"How is a population of final cells maintained? A compartmental branching approach for cell differentiation"

Cell differentiation is a process through which a generic cell evolves into a given type of cell, usually into a more specialized type. Cells of the human body have nearly identical genome but exhibit very different phenotypes that allow them to carry out specific functions and react to changes in the surrounding environment. We can model cells sharing the same surface attributes (same phenotype) as belonging to the same mathematical state (or compartment). Cells can either die, divide or change phenotype (entering another compartment). We derive a cell-compartmental model for cell differentiation; by defining a family of random variables we can model the progeny of a founder cell as a stochastic process. We can describe the evolution of mean quantities by a set of ordinary differential equations and we analyse a number of summary statistics to bring insight to the understanding of cellular dynamics. We show, with two case studies from Cellular Immunology, how our mathematical techniques can shed light on the dynamics of cell differentiation in different systems.

Sakurako Tanida

The University of Tokyo

"Organoid morphogenesis at various luminal fluid pressure and proliferation time in a multicellular phase-field model"

Organoids are self-organizing cells that are grown from stem cells in vitro and are widely used to model organ development and disease. In organoids, while cell growth and hence proliferation are mechanically constrained due to the geometrical requirements to keep maintaining the cell cluster, various morphologies of organoids are achieved. However, it remains elusive how such mechanical constraint can affect organoid growth and the final morphology. In this study, we investigate the influences of mechanical constraint on organoid morphogenesis by numerical simulations with a multicellular phase-field model. In this mathematical model, we can isolate out mechanical interaction from other biological processes. More specifically, we examine the pattern formations of organoids emerging when changing luminal fluid pressure and proliferation time. Even if most organoids seem to be the same in the initial phase, they have distinctive features in the later phase in this numerical model. The patterns in the later phase include spheroid-like shape, star-like shape, and so on. Although all cells have identical natures, in the star-like organoid, cells that can divide are spatially fixed and show behavior like spontaneous differentiation. Classifying the patterns of organoids by several indexes, we discuss the mechanisms which generate the different pattern.

Kana Fuji

The University of Tokyo

"Lumenogenesis simulations of organoids using a multicellular phase-field model with molecules of apical components"

Organoids are three-dimensional cultured organ models grown from stem cells. Epithelial organoids which have apico-basal polarity in each cell form lumens on the apical side and the lumens grow during the cell self-organization process. In addition to osmotic pressure in luminal fluid and cortical tension, the presence of non-adhesive apical membranes is involved in luminal area expansion recently. However, it remains unclear how the lumenogenesis processes were affected localized adhesive property changes in the membrane. In this study, to investigate the luminal pattern formed by cells with localized non-adhesive membranes, we extended the multicellular phase-field model with luminal fluid to a multicellular model with polarity by introducing the molecules of the apical component. The results of simulations with this model showed that lumens were formed even at pressures lower than the pressure required for the lumen growth without the introduction of the cell polarity. This model reproduces not only the round lumen but also the squeezed lumen that was not available in the previous models. In this talk, we will discuss the quantitative analysis of the lumen structure and its comparison with experiments.

Mete Demircigil

Institut Camille Jordan, Lyon

"Aerotactic Waves in Dictyostelium discoideum : When Self-Generated Gradients engage with Expansion by Cell Division."

Using a self-generated hypoxic assay, it is shown that Dictyostelium discoideum displays a remarkable collective aerotactic behavior: when a cell colony is covered, cells quickly consume the available oxygen and form a dense ring moving outwards at constant speed and density. We propose a simple, yet original PDE model, that enables an analytical qualitative and quantitative study of the phenomenon and reveals that the collective migration can be explained by the interplay between cell division and the modulation of aerotaxis. The modeling and its conclusions supplement and are confirmed by an experimental investigation of the cell population behavior. This approach also gives rise to an explicit and novel formula of the collective migration speed of cells that encapsulates a surprising combination of expansion by cell divison, such as described by the Fisher/KPP equation, and aerotaxis. The conclusions of this model appear to extend to more complex models.This is joint work with Christophe ANJARD Vincent CALVEZ, Jean-Paul RIEU, Olivier COCHET-ESCARTIN and and is a subpart of the work presented in the preprint bioRxiv 2020.08.17.246082; doi: https://doi.org/10.1101/2020.08.17.246082.