Open AccessExploring the mechanism of pancreatic cell fate decisions via cell-cell communication
Author(s) -
Dasong Huang,
Ruiqi Wang
Publication year - 2021
Publication title -
mathematical biosciences and engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.451
H-Index - 45
eISSN - 1551-0018
pISSN - 1547-1063
DOI - 10.3934/mbe.2021122
Subject(s) - cell fate determination , pancreas , notch signaling pathway , microbiology and biotechnology , endocrine system , biology , enteroendocrine cell , progenitor cell , endoderm , medicine , endocrinology , cellular differentiation , signal transduction , stem cell , transcription factor , hormone , biochemistry , gene
The endocrine and exocrine cells in pancreas originate initially from a group of apparently identical endoderm cells in the early gut. The endocrine and exocrine tissues are composed of islet/acinar and duct cells respectively. To explore the mechanism of pancreas cell fate decisions, we first construct a minimal mathematical model related to pancreatic regulations. The regulatory mechanism of acinar-to-islet cell conversion is revealed by bifurcation analysis of the model. In addition, Notch signaling is critical in determining the fate of endocrine and exocrine in the developing pancreas and it is a typical mediator of lateral inhibition which instructs adjacent cells to make different fate decisions. Next, we construct a multicellular model of cell-cell communication mediated by Notch signaling with trans-activation and cis-inhibition. The roles of Notch signaling in regulating fate decisions of endocrine and exocrine cells during the differentiation of pancreatic cells are explored. The results indicate that high (or low) level of Notch signaling drive cells to select the fate of exocrine (or endocrine) progenitor cells. The networks and the models presented here might be good candidates for providing qualitative mechanisms of pancreatic cell fate decisions. These results can also provide some insight on choosing perturbation strategies for further experimental analysis.