2021/07/09 by Simon Schardt, Schardt, Simon, Sabine Fischer +1
Biochemistry, Genetics and Molecular Biology · #Biological Physics (physics.bio-ph) #Dynamical Systems (math.DS) #FOS: Biological sciences #FOS: Mathematics #FOS: Physical sciences #Gene Regulatory Network Analysis #Pluripotent Stem Cells Research #Single-cell and spatial transcriptomics #Tissues and Organs (q-bio.TO)
paper · pdf · doi:10.48550/arxiv.2107.04501
openalex publication_date 2021/07/09 · openalex created_date 2022/07/25 · openalex updated_date 2026/07/28
In preimplantation mammalian embryos, the second cell fate decision\nintroduces spatial patterns of embryonic and extra-embryonic precursor cells.\nThe transcription factors NANOG and GATA6 are the earliest markers for the two\ncell types and interact between cells via the fibroblast growth factor\nsignaling pathway. Computational models have been used to mimic the patterns\nand cell type proportions found in experimental studies. However, these models\nare always phenomenological in nature and lack a proper physical explanation.\nWe derive a cell fate decision model motivated by the ideas of statistical\nmechanics. The model incorporates intra- and intercellular interactions of\nNANOG and GATA6. A detailed mathematical analysis on the resulting dynamical\nsystem is presented. We find that our model is capable of generating tissue\nwide spatial patterns of the two cell types. Its advantages are revealed in the\nsimple physical and biological interpretation of the parameters and their\ninteractions. In numerical simulations, we showcase the ability to replicate\ncheckerboard patterns of different cell type proportions varying only a single\nparameter. The tight control of the system as well as the ease of use and the\ndirect expandability to other signaling types provide solid reasons for the\ncontinued use of our model. We are convinced that our approach presents an\nexciting perspective in relation to cell fate decisions. Moreover, the concepts\nare generalizable to questions regarding cell signaling beyond the mammalian\nembryo.\n