A computational model of stem cells’ decision-making mechanism to maintain tissue homeostasis and organization in the presence of stochasticity

Abstract

The maintenance of multi-cellular developed tissue depends on the proper cell production rate to replace the cells destroyed by the programmed process of cell death. The stem cell is the main source of producing cells in a developed normal tissue. It makes the stem cell the lead role in the scene of a fully formed developed tissue to fulfill its proper functionality. By focusing on the impact of stochasticity, here, we propose a computational model to reveal the internal mechanism of a stem cell, which generates the right proportion of different types of specialized cells, distribute them into their right position, and in the presence of intercellular reactions, maintain the organized structure in a homeostatic state. The result demonstrates that the spatial pattern could be harassed by the population geometries. Besides, it clearly shows that our model with progenitor cells able to recover the stem cell presence could retrieve the initial pattern appropriately in the case of injury. One of the fascinating outcomes of this project is demonstrating the contradictory roles of stochasticity. It breaks the proper boundaries of the initial spatial pattern in the population. While, on the flip side of the coin, it is the exact factor that provides the demanded non-genetic diversity in the tissue. The remarkable characteristic of the introduced model as the stem cells’ internal mechanism is that it could control the overall behavior of the population without need for any external factors.

Correspondence between Signaling and Developmental Patterns by Competing Cells: A Computational Perspective

“…Indeed, by mapping the environmental signaling patterns to the probability of the emergence of differentiated cell types, this model is capable of capturing any desired complex pattern, whether passive or active. The sort of models that recapitulates signaling dynamics and predicts cell fate patterning upon chemical perturbations preceedingly has been investigated in non-competitive environments 15,25,[32][33][34][35][36] . However, here, we focused on the behavior of each cell in interaction with diverse and competing signals.…”

“…Remarkably, specific networks are capable of creating patterns using signals without the constraint of relative diffusion rates. Internal mechanisms are responsible for generating the right proportion of different types of specialized cells, distributing them into their right position, and maintaining the organized structure in the presence of intercellular chemical signaling agents 15 . Cells also sense and respond to mechanical stimuli and the physical properties of their environment via induced downstream genetic regulatory networks [16][17][18] .…”

“…Cells also sense and respond to mechanical stimuli and the physical properties of their environment via induced downstream genetic regulatory networks [16][17][18] . Several multi-stable regulatory networks play their role as the internal decision-makers of dividing cells 15 . This study investigates the impact of various chemical signals on the mechanism by which multiple stem cells generate intricate tissue structures and tries to provide a deeper understanding of the mechanisms behind morphological variation.…”

A computational model of stem cells’ internal mechanism to recapitulate spatial patterning and maintain the self-organized pattern in the homeostasis state

“…To fulfill this, we need to develop a mathematical model to recapitulate the stem cells’ internal mechanisms in order to: first, regulate the required non-genetic diversity in the tissue by orchestrating proliferation and differentiation in stem cells, second, organize the population of cells in a desired spatial arrangement, and third, maintain the structure of the population in the dynamic stochastic environment of a living tissue 1 . This will help us to understand mechanistically the critical building blocks of living systems, stem cells, to identify components that can be modified through stem-cell-based therapies to control mysterious phenomena such as aging, and cancer, and generate spatially ordered tissues for therapeutic purposes 2 , 3 .…”

“…Prior research underscores the importance of population heterogeneity arising from genetically similar stem cells 2 , 3 . This heterogeneity is critical for maintaining a balance between proliferation and differentiation, ensuring the continued existence of the main source of population (SCs) as well as specialized cells with vital role in preserving the tissue’s functionality.…”