deBack2013 - Pancreas differentiation patterning in spatio-temporal multicellular model
This model reproduces a solution (at a=1, b=20.8, eta=1e-4) of the parameter scan in Fig. 4b of the referenced paper. Equations and other parameter values are as published. Notch signaling in competition with lateral stabilization, both mediated by cell–cell interactions, can control the cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages and yield a scattered spatial distribution of endocrine cells, major constituents of the later islets of Langerhans. The model file is in MorpheusML format and can be opened in the free, open-source multicellular modeling software Morpheus to simulate the time course (movie) of lineage specification in 10.000 coupled cells in the early pancreatic tissue. Creator of Morpheus model: email@example.com Date of Morpheus model: 21/09/2012 Software: Morpheus (free, open-source), download from https://morpheus.gitlab.io
- On the role of lateral stabilization during early patterning in the pancreas.
- de Back W, Zhou JX, Brusch L
- Journal of the Royal Society, Interface , 2/ 2013 , Volume 10 , pages: 20120766 , PubMed ID: 23193107
- Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.
- The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell-cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell-cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development.
Peter Brusch, Krishna Kumar Tiwari
|Pancreas_Differentiation.xml||MorpheusML||6.55 KB||Preview | Download|
|Pancreas_Differentiation.mp4||mpeg4 movie of the model simulation||884.52 KB||Preview | Download|