RT Journal Article
SR Electronic
T1 Enhanced Waddington Landscape Model with Cell-Cell Communication Can Explain Molecular Mechanisms of Self-Organization
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 241604
DO 10.1101/241604
A1 H. Fooladi
A1 P. Moradi
A1 A. Sharifi-Zarchi
A1 B. H. Khalaj
YR 2018
UL http://biorxiv.org/content/early/2018/01/01/241604.abstract
AB The molecular mechanisms of self-organization that orchestrate embryonic cells to create astonishing patterns have been among major questions of developmental biology. It is recently shown that embryonic stem cells (ESCs), when cultured on particular micropatterns, can self-organize and mimic early steps of pre-implantation embryogenesis. A systems-biology model to address this observation from a dynamical systems perspective is essential. Here, we propose a multicellular mathematical model for pattern formation during in vitro gastrulation of human ESCs. This model enhances the basic principles of Waddington epigenetic landscape with cell-cell communication, in order to enable pattern and tissue formation. To prevent overfitting of the model, there is a minimal number of parameters in the model, which are sufficient to address different experimental observations such as the formation of three germ layers and trophectoderm, responses to altered culture conditions and micropattern diameters, and unexpected spotted forms of the germ layers under certain conditions. This model provides a basis for in-silico modeling of self-organization.