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.