Biology subjects

Stopka, A.

Publications and source records attributed to Stopka, A..

3 recordsLinked to original sources

bioRxiv2019

Cell-based simulations of Notch-dependent cell differentiation on growing domains

Notch signalling controls cell differentiation and proliferation in many tissues. The Notch signal is generated by the interaction between the Notch receptor of one cell with the Notch ligand (Delta or Jagged) of a neighbouring cell. Therefore, the pathway requires cell-cell contact in order to be active. During organ development, cell differentiation occurs concurrently with tissue growth and changes in cell morphology. How growth impacts on Notch signalling and cell differentiation remains poorly understood. Here, we developed a modelling environment to simulate Notch signalling in a growing tissue. We use our model to simulate the differentiation process of pancreatic progenitor cells. Our results suggest that Notch-mediated differentiation in the developing pancreas is first mediated by geometric effects that result in loss of Notch signalling on the tissue boundary, leading to the differentiation of tip versus trunk cells. A second wave of differentiation further happens in the trunk cells due to a reduction in the expression of the ligand Jagged, which has been shown to be controlled by signalling factors secreted from the surrounding mesenchyme. Our results bring new insights into how cells coordinate tissue growth with cell fate specification during organ development.

developmental biology↗

bioRxiv2019

Cell-based Simulations of Biased Epithelial Lung Growth

During morphogenesis, epithelial tubes elongate. In case of the mammalian lung, biased elongation has been linked to a bias in cell shape and cell division, but it has remained unclear whether a bias in cell shape along the axis of outgrowth is sufficient for biased outgrowth and how it arises. Here, we use our 2D cell-based tissue simulation software LBIBCell to investigate the conditions for biased epithelial outgrowth. We show that the observed bias in cell shape and cell division can result in the observed bias in outgrowth only in case of strong cortical tension, and comparison to biological data suggests that the cortical tension in epithelia is likely sufficient. We explore mechanisms that may result in the observed bias in cell division and cell shapes. To this end, we test the possibility that the surrounding tissue or extracellular matrix acts as a mechanical constraint that biases growth in longitudinal direction. While external compressive forces can result in the observed bias in outgrowth, we find that they do not result in the observed bias in cell shapes. We conclude that other mechanisms must exist that generate the bias in lung epithelial outgrowth.

biophysics↗

bioRxiv2019

A stochastic model of adult neurogenesis coupling cell cycle progression and differentiation

Long-term tissue homeostasis requires a precise balance between stem cell self-renewal and the generation of differentiated progeny. Recently, it has been shown that in the adult murine brain, neural stem cells (NSCs) divide mostly symmetrically. This finding suggests that the required balance for tissue homeostasis is accomplished at the population level. However, it remains unclear how this balance is enabled. Furthermore, there is experimental evidence that proneural differentiation factors not only promote differentiation, but also cell cycle progression, suggesting a link between the two processes in NSCs. To study the effect of such a link on NSC dynamics, we developed a stochastic model in which stem cells have an intrinsic probability to progress through cell cycle and to differentiate. Our results show that increasing heterogeneity in differentiation probabilities leads to a decreased probability of long-term tissue homeostasis, and that this effect can be compensated when cell cycle progression and differentiation are positively coupled. Using single-cell RNA-Seq profiling of adult NSCs, we found a positive correlation in the expression levels of cell cycle and differentiation markers. Our findings suggest that a coupling between cell cycle progression and differentiation on the cellular level is part of the process that maintains tissue homeostasis in the adult brain.

neuroscience↗