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Enhanced Waddington landscape model with cell-cell communication can explain molecular mechanisms of self-organization

Fooladi, H ; Sharif University of Technology | 2019

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  1. Type of Document: Article
  2. DOI: 10.1093/bioinformatics/btz201
  3. Publisher: Oxford University Press , 2019
  4. Abstract:
  5. 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 in particular micropatterns, can self-organize and mimic the early steps of pre-implantation embryogenesis. A systems-biology model to address this observation from a dynamical systems perspective is essential and can enhance understanding of the phenomenon. Results: 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. We have shown the sufficiency of a simple mechanism by using a minimal number of parameters in the model, in order to address a variety of 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. Moreover, we have tested different boundary conditions as well as various shapes, observing that the pattern is initiated from the boundary and gradually spreads towards the center. This model provides a basis for in-silico modeling of self-organization. Availability and implementation: https://github.com/HFooladi/Self-Organization. Supplementary information: Supplementary data are available at Bioinformatics online. © 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved
  6. Keywords:
  7. Article ; Bioinformatics ; Body patterning ; Cell communication ; Computer model ; Epigenetics ; Gastrulation ; Germ layer ; Human cell ; Human embryonic stem cell ; In vitro study ; Systems biology ; Trophoblast
  8. Source: Bioinformatics ; Volume 35, Issue 20 , 2019 , Pages 4081-4088 ; 13674803 (ISSN)
  9. URL: https://academic.oup.com/bioinformatics/article/35/20/4081/5418791