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Transcription factors FOXO in the regulation of homeostatic hematopoiesis

Menon, Vijaya; Ghaffari, Saghia,b,c

Current Opinion in Hematology: July 2018 - Volume 25 - Issue 4 - p 290–298
doi: 10.1097/MOH.0000000000000441
HEMATOPOIESIS: Edited by Hal E. Broxmeyer

Purpose of review Work in the past decade has revealed key functions of the evolutionary conserved transcription factors Forkhead box O (FOXO) in the maintenance of homeostatic hematopoiesis. Here the diverse array of FOXO functions in normal and diseased hematopoietic stem and progenitor cells is reviewed and the main findings in the past decade are highlighted. Future work should reveal FOXO-regulated networks whose alterations contribute to hematological disorders.

Recent findings Recent studies have identified unanticipated FOXO functions in hematopoiesis including in hematopoietic stem and progenitor cells (HSPC), erythroid cells, and immune cells. These findings suggest FOXO3 is critical for the regulation of mitochondrial and metabolic processes in hematopoietic stem cells, the balanced lineage determination, the T and B homeostasis, and terminal erythroblast maturation and red blood cell production. In aggregate these findings highlight the context-dependent function of FOXO in hematopoietic cells. Recent findings also question the nature of FOXO's contribution to heme malignancies as well as the mechanisms underlying FOXO's regulation in HSPC.

Summary FOXO are safeguards of homeostatic hematopoiesis. FOXO networks and their regulators and coactivators in HSPC are greatly complex and less well described. Identifications and characterizations of these FOXO networks in disease are likely to uncover disease-promoting mechanisms.

aDepartment of Cell, Developmental and Regenerative Biology

bBlack Family Stem Cell Institute

cTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA

Correspondence to Saghi Ghaffari, MD, PhD, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA. Tel: +1 212 659 8271; fax: +1 212-803-6740; e-mail: Saghi.Ghaffari@mssm.edu

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