Hematopoietic lineage commitment is regulated by cytokines and master transcription factors, but it remains unclear how a progenitor cell chooses a lineage in the face of conflicting cues. Through transcript counting in megakaryocyte-erythroid progenitors undergoing erythropoiesis, we show that expression levels of pro-erythropoiesis transcription factor EKLF and receptor EpoR are negatively correlated with pro-megakaryocyte counterparts, FLI-1 and TpoR. Based on these findings, we propose a new model for exclusive decision-making and we experimentally confirm a model prediction of transcript noise levels in committing progenitors. Our study suggests that lineage-specific receptor levels can modulate cue potencies to achieve robust commitment decisions.
- Received June 20, 2014.
- Accepted July 6, 2015.
- © 2015. Published by The Company of Biologists Ltd