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Títol: Morphogenetic signaling propagation in a heterotypic assembloid

Estudiant que ha llegit aquest projecte:

Tutor/a o Cotutor/a: PRATS SOLER, CLARA

Departament: FIS

Títol: Morphogenetic signaling propagation in a heterotypic assembloid

Data inici oferta: 21-01-2025      Data finalització oferta: 31-01-2025

Estudis d'assignació del projecte:
    GR ENG SIS BIOLÒG 23

Lloc de realització:

UPC      Departament/centre: Departament de Física, EPSEB

Segon tutor/a extern: DAVID ORIOLA SANTANDREU (UPC)

Paraules clau:
Cell differentiation, 3D tissue patterning, computational model, reaction-diffusion, signaling propagation

Descripció del contingut i pla d'activitats:
Cells in a developing embryo communicate with their neighbors to orchestrate differentiation and tissue patterning. The mechanisms by which morphogenetic signals propagate through 3D tissues are complex, as cells not only exchange signaling molecules but also actively move within the tissue. In this study, we focus on the spatiotemporal dynamics of the T-box transcription factor Brachyury/T (Bra/T), a key mesodermal marker during anteroposterior axis formation in embryos. We investigate signaling propagation in vitro in a heterotypic assembloid, formed by fusing Bra/T+ and a Bra/T- tissue spheroids. We analyze how Bra/T signaling is transduced from the Bra/T+ tissue to the Bra/T- tissue and propose a simple reaction-diffusion model to account for the experimental observations. Finally, we explore how signaling propagation is affected by the size of the 3D tissue spheroids.

Overview (resum en anglès): Gastruloids are three-dimensional aggregates of embryonic stem cells capable of self-organization in vitro and of reproducing key processes of early embryonic development, such as symmetry breaking and the establishment of the anteroposterior axis. This process is characterized by the polarized expression of the Brachyury/T (Bra/T) gene, associated with mesoderm differentiation, making gastruloids a relevant model for the quantitative study of cellular self-organization.
The main objective of this work is to analyze the spatial dynamics of the Bra/T-positive cell population during symmetry breaking in gastruloids and to evaluate the ability of different reaction-diffusion mathematical models to describe the experimentally observed spatial profiles and to extract biologically interpretable parameters.
To this end, experimental imaging data were used to extract fluorescence profiles along the anteroposterior axis. These profiles were quantitatively analyzed and fitted using effective diffusion models and reaction-diffusion models of increasing complexity.
The results show that models based solely on pure diffusion or linear schemes capture global trends but fail to reproduce the detailed spatial structure of the profiles. In contrast, the inclusion of nonlinear regulatory mechanisms significantly improves the quality of the fits, indicating that the system dynamics correspond to a regulated collective process.
Finally, a robust estimation of the effective diffusion coefficient, D_B, associated with the Bra/T-positive population inferred from the quantitative analysis of the temporal evolution of spatial fluorescence profiles through the fitting of mathematical models, was obtained. The estimated values are consistent with collective cell mobility processes in dense tissues. Overall, this work highlights the potential of gastruloids as model systems for the quantitative study of symmetry breaking in vitro.

Aquest projecte està relacionat amb l'adaptació al Canvi Climatic? No

Aquest projecte està relacionat amb la digitalització del seu àmbit de treball? No

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