The Transcription Factor E74-Like Factor Controls Quiescence of Endothelial Cells and Their Resistance to Myeloablative Treatments in Bone Marrow
Objective—The regeneration of the hematopoietic system in bone marrow after chemotherapy depends on a balance between the quiescence and proliferation of lineage-specific progenitor cells. Even though the vascular network in bone is damaged by cytoablation, the transcriptional control of quiescence in endothelial cells is not well known. In this study, we investigated the role of the transcription factor E74-like factor (ELF4) in the proliferation of endothelial cells in bone marrow.
Methods and Results—Loss-of-function models were used to study the role of ELF4 in human and murine endothelial cells. ELF4 promotes cell cycle entry by activating cyclin-dependent kinase-4 in human umbilical vein endothelial cells. Elf4-null mice exhibited enhanced recovery of bone marrow CD45− CD31+ endothelial cells and sinusoidal blood vessels following administration of 5-fluorouracil.
Conclusion—Loss of ELF4 leads to increased quiescence in bone marrow endothelial cells by the deregulation of cyclin-dependent kinase-4 expression and to enhanced regeneration of sinusoidal blood vessels.
- Received March 18, 2010.
- Accepted February 10, 2011.
- © 2011 American Heart Association, Inc.