A Systems Approach Identifies Essential FOXO3 Functions at Key Steps of Terminal Erythropoiesis.

ABSTRACT: Circulating red blood cells (RBCs) are essential for tissue oxygenation and homeostasis. Defective terminal erythropoiesis contributes to decreased generation of RBCs in many disorders. Specifically, ineffective nuclear expulsion (enucleation) during terminal maturation is an obstacle to therapeutic RBC production in vitro. To obtain mechanistic insights into terminal erythropoiesis we focused on FOXO3, a transcription factor implicated in erythroid disorders. Using an integrated computational and experimental systems biology approach, we show that FOXO3 is essential for the correct temporal gene expression during terminal erythropoiesis. We demonstrate that the FOXO3-dependent genetic network has critical physiological functions at key steps of terminal erythropoiesis including enucleatio

SUBMITTER: Liang R 

PROVIDER: S-EPMC4599908 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature