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Title: The transcription factor E74-like factor controls quiescence of endothelial cells and their resistance to myeloablative treatments in bone marrow

Author
item SIVINA, MARIELA - Baylor College Of Medicine
item YAMADA, TAKESHI - Baylor College Of Medicine
item PARK, CHUN - Baylor College Of Medicine
item PUPPI, MONICA - Baylor College Of Medicine
item COSKUN, SULEYMAN - Baylor College Of Medicine
item HIRSCHI, KAREN - Children'S Nutrition Research Center (CNRC)
item LACORAZZA, H - Baylor College Of Medicine

Submitted to: Arteriosclerosis Thrombosis and Vascular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/10/2011
Publication Date: 3/1/2011
Citation: Sivina, M., Yamada, T., Park, C.S., Puppi, M., Coskun, S., Hirschi, K., Lacorazza, H.D. 2011. The transcription factor E74-like factor controls quiescence of endothelial cells and their resistance to myeloablative treatments in bone marrow. Arteriosclerosis Thrombosis and Vascular Biology. 31(5):1185-1191.

Interpretive Summary: The regeneration of the blood and all blood-related cells throughout the circulatory system (also known as the hematopoietic system) in bone marrow after chemotherapy depends on a balance between the quiescence (when cells aren’t dividing) and proliferation (when cells are actively dividing) of lineage-specific progenitor cells. Even though blood vessels in bone are damaged, the transcriptional control of quiescence in endothelial cells is not well known. In this study, we investigated the role of a transcription factor (ELF4) in the proliferation of endothelial cells in bone marrow. Certain models were used to study the role of ELF4 in specific human and mouse cells. We found that ELF4 causes cells to proliferate; and alternatively, the loss of ELF4 leads to increased quiescence in bone marrow endothelial cells.

Technical Abstract: 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. 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. 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.