An Effective Model of HL-60 Differentiation

BioRxiv : the Preprint Server for Biology
Ryan TasseffJeffrey D Varner


We present an effective model All-Trans Retinoic Acid (ATRA)-induced differentiation of HL-60 cells. The model describes a key architectural feature of ATRA-induced differen- tiation, positive feedback between an ATRA-inducible signalsome complex involving many proteins including Vav1, a guanine nucleotide exchange factor, and the activation of the mitogen activated protein kinase (MAPK) cascade. The model, which was developed by integrating logical rules with kinetic model- ing, was significantly smaller than previous models. However, despite its simplicity, it captured key features of ATRA induced differentiation of HL-60 cells. We identified an ensemble of effec- tive model parameters using measurements taken from ATRA- induced HL-60 cells. Using these parameters, model analysis predicted that MAPK activation was bistable as a function of ATRA exposure. Conformational experiments supported ATRA- induced bistability. These findings, combined with other literature evidence, suggest that positive feedback is central to a diversity of cell fate programs.

Related Concepts

Cell Differentiation Process
Guanine Nucleotide Exchange Factors
Mitogen-Activated Protein Kinase Kinases
HL-60 Cells
Research Study
Peptidylarginine deiminase type IV

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.