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

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Red blood cells (RBCs) are highly specialized cells that transport oxygen throughout the body and are essential for survival. However, RBCs have a limited lifespan and need to be replenished continuously by stem cells in the bone marrow. Mammalian RBCs are unique in that in order to fully mature they exclude their nucleus and other organelles. Mechanisms involved in these processes are not well understood at the molecular level. Defects in any of the these processes may lead to red blood cell defects, a decreased capacity to transport oxygen and/or a block in red blood cell production in vitro. Therefore, understanding how these processes are regulated at the molecular level can lead to promising new therapies for red blood cell defects and improved methods of generating red blood cells in a dish. Here, using an integrated computational and experimental biology approach, we found that the nuclear factor FOXO3 is a crucial regulator of red blood cell production by coordinating the expression of many of the genes specific for terminal maturation of red blood cells. Furthermore we found that FOXO3 can even increase the production of normal red blood cells in culture raising the possibility that enhancing FOXO3 may have a therapeutic use. Our studies identify FOXO3 as a novel regulator of RBC enucleation and terminal erythropoiesis.

Vyšlo v časopise: A Systems Approach Identifies Essential FOXO3 Functions at Key Steps of Terminal Erythropoiesis. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005526
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005526

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