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. CONCLUSIONS: 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.
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. CONCLUSIONS: 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.
Authors: H Daniel Lacorazza; Yasushi Miyazaki; Antonio Di Cristofano; Anthony Deblasio; Cyrus Hedvat; Jin Zhang; Carlos Cordon-Cardo; Shifeng Mao; Pier Paolo Pandolfi; Stephen D Nimer Journal: Immunity Date: 2002-10 Impact factor: 31.745
Authors: D D Spyropoulos; P N Pharr; K R Lavenburg; P Jackers; T S Papas; M Ogawa; D K Watson Journal: Mol Cell Biol Date: 2000-08 Impact factor: 4.272
Authors: Carsten Müller-Tidow; Björn Steffen; Thomas Cauvet; Lara Tickenbrock; Ping Ji; Sven Diederichs; Bülent Sargin; Gabriele Köhler; Matthias Stelljes; Elena Puccetti; Martin Ruthardt; Sven deVos; Scott W Hiebert; H Phillip Koeffler; Wolfgang E Berdel; Hubert Serve Journal: Mol Cell Biol Date: 2004-04 Impact factor: 4.272