title: The transcription factor E74-like factor controls quiescence of endothelial cells and their resistance to myeloablative treatments in bone marrow.
abstract: 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.
  
  
  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.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital, 1102 Bates St, Ste 830, Houston, TX 77030, USA.
authors.forename: Mariela
authors.initials: M
authors.lastname: Sivina
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Chun Shik
authors.initials: CS
authors.lastname: Park
authors.forename: Monica
authors.initials: M
authors.lastname: Puppi
authors.forename: Suleyman
authors.initials: S
authors.lastname: Coskun
authors.forename: Karen
authors.initials: K
authors.lastname: Hirschi
authors.forename: H Daniel
authors.initials: HD
authors.lastname: Lacorazza
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D019556:COS Cells; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D002522:Chlorocebus aethiops; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004351:Drug Resistance; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019653:Myeloablative Agonists / Q000494:pharmacology*; D041681:NIH 3T3 Cells; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C111931:ELF4 protein, human; C491779:Elf4 protein, mouse; D019653:Myeloablative Agonists; D014157:Transcription Factors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D005472:Fluorouracil