TY - JOUR
AU - Smith-Miles, Kate
AB - Background: Hematopoiesis is a highly orchestrated developmental process that comprises various developmental stages of the hematopoietic stem cells (HSCs). During development, the decision to leave the self-renewing state and selection of a differentiation pathway is regulated by a number of transcription factors. Among them, genes GATA-1 and PU.1 form a core negative feedback module to regulate the genetic switching between the cell fate choices of HSCs. Although extensive experimental studies have revealed the mechanisms to regulate the expression of these two genes, it is still unclear how this simple module regulates the genetic switching. Methods: In this work we proposed a mathematical model to study the mechanisms of the GATA-PU.1 gene network in the determination of HSC differentiation pathways. We incorporated the mechanisms of GATA switch into the module, and developed a mathematical model that comprises three genes GATA-1, GATA-2 and PU.1. In addition, a novel multiple-objective optimization method was designed to infer unknown parameters in the proposed model by realizing different experimental observations. A stochastic model was also designed to describe the critical function of noise, due to the small copy numbers of molecular species, in determining the differentiation pathways. Results: The proposed deterministic model has successfully realized 
TI - Mathematical modeling of GATA-switching for regulating the differentiation of hematopoietic stem cell
JF - BMC Systems Biology
DO - 10.1186/1752-0509-8-S1-S8
DA - 2014-01-24
UR - https://www.deepdyve.com/lp/springer-journals/mathematical-modeling-of-gata-switching-for-regulating-the-YA70L01XGH
SP - 1
EP - 12
VL - 8
IS - 1
DP - DeepDyve
ER -