Integrating extrinsic and intrinsic cues into a minimal model of lineage commitment for hematopoietic progenitors.

Integrating extrinsic and intrinsic cues into a minimal model of lineage commitment for hematopoietic progenitors.

Blog Article

Autoregulation of transcription factors and cross-antagonism between lineage-specific transcription factors are a recurrent theme in cell differentiation.An equally prevalent event that is frequently overlooked in lineage commitment models is the upregulation of lineage-specific receptors, often through lineage-specific transcription factors.Here, we use a minimal model that combines cell-extrinsic and cell-intrinsic elements of regulation in order to understand how both instructive and stochastic events can inform cell commitment decisions in hematopoiesis.Our results suggest that Mushroom Vapes cytokine-mediated positive receptor feedback can induce a "switch-like" response to external stimuli during multilineage differentiation by providing robustness to both bipotent and committed states while protecting progenitors from noise-induced differentiation or decommitment.

Our model provides support to both the instructive and stochastic theories of commitment: cell fates are ultimately driven by lineage-specific transcription factors, but cytokine signaling can strongly bias lineage commitment by regulating these inherently noisy cell-fate decisions with complex, pertinent behaviors such as ligand-mediated ultrasensitivity and robust multistability.The simulations further suggest that sippy cups the kinetics of differentiation to a mature cell state can depend on the starting progenitor state as well as on the route of commitment that is chosen.Lastly, our model shows good agreement with lineage-specific receptor expression kinetics from microarray experiments and provides a computational framework that can integrate both classical and alternative commitment paths in hematopoiesis that have been observed experimentally.