PT - JOURNAL ARTICLE AU - Shah, Najaf A. AU - Levesque, Marshall J. AU - Raj, Arjun AU - Sarkar, Casim A. TI - Robust hematopoietic progenitor cell commitment in the presence of a conflicting cue AID - 10.1242/jcs.158436 DP - 2015 Aug 15 TA - Journal of Cell Science PG - 3009--3017 VI - 128 IP - 16 4099 - http://jcs.biologists.org/content/128/16/3009.short 4100 - http://jcs.biologists.org/content/128/16/3009.full SO - J. Cell Sci.2015 Aug 15; 128 AB - 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 the expression levels of the pro-erythropoiesis transcription factor EKLF (also known as KLF1) and receptor EpoR are inversely correlated with their pro-megakaryopoiesis counterparts, FLI-1 and TpoR (also known as MPL). Notably, as progenitors commit to the erythrocyte lineage, EpoR is upregulated and TpoR is strongly downregulated, thus boosting the potency of the pro-erythropoiesis cue erythropoietin and effectively eliminating the activity of the pro-megakaryopoiesis cue thrombopoietin. Based on these findings, we propose a new model for exclusive decision making that explicitly incorporates signals from extrinsic cues, and we experimentally confirm a model prediction of temporal changes in transcript noise levels in committing progenitors. Our study suggests that lineage-specific receptor levels can modulate potencies of cues to achieve robust commitment decisions.