TY - JOUR
T1 - The transcription factor MEF/ELF4 regulates the quiescence of primitive hematopoietic cells
AU - Lacorazza, H. Daniel
AU - Yamada, Takeshi
AU - Liu, Yan
AU - Miyata, Yasuhiko
AU - Sivina, Mariela
AU - Nunes, Juliana
AU - Nimer, Stephen D.
N1 - Funding Information:
The authors would like to thank the staff of the Flow Cytometry and Mouse Genotyping Core Facilities in MSKCC. We are also grateful to Dr. Margaret Goodell for her suggestions on conducting SP analysis; to Drs. John Petrini, Malcolm Moore, and Vladimir Jankovic for their critical review of our manuscript; to Cyrus Hedvat for his assistance in siRNA design; and to Christopher Threeton for the SP detection at Texas Children's Hospital. This work was funded by NIH RO1 DK52208 (S.D.N.), a Howard Temin Award from NCI/NIH to H.D.L. (KO1-CA099156), the Moran Foundation Award (H.D.L.), the Curtis Hankamer Basic Research Fund (Junior-Faculty Seed Fund Award, Baylor College of Medicine; H.D.L.), and The Laurie Strauss Leukemia Foundation Award (H.D.L.).
PY - 2006/3
Y1 - 2006/3
N2 - The transcriptional circuitry that regulates the quiescence of hematopoietic stem cells is largely unknown. We report that the transcription factor known as MEF (or ELF4), which is targeted by the t(X;21)(q26;q22) in acute myelogenous leukemia, regulates the proliferation of primitive hematopoietic progenitor cells at steady state, controlling their quiescence. Mef null HSCs display increased residence in G0 with reduced 5-bromodeoxyuridine incorporation in vivo and impaired cytokine-driven proliferation in vitro. Due to their increased HSC quiescence, Mef null mice are relatively resistant to the myelosuppressive effects of chemotherapy and radiation. Thus, MEF plays an important role in the decision of stem/primitive progenitor cells to divide or remain quiescent by regulating their entry to the cell cycle.
AB - The transcriptional circuitry that regulates the quiescence of hematopoietic stem cells is largely unknown. We report that the transcription factor known as MEF (or ELF4), which is targeted by the t(X;21)(q26;q22) in acute myelogenous leukemia, regulates the proliferation of primitive hematopoietic progenitor cells at steady state, controlling their quiescence. Mef null HSCs display increased residence in G0 with reduced 5-bromodeoxyuridine incorporation in vivo and impaired cytokine-driven proliferation in vitro. Due to their increased HSC quiescence, Mef null mice are relatively resistant to the myelosuppressive effects of chemotherapy and radiation. Thus, MEF plays an important role in the decision of stem/primitive progenitor cells to divide or remain quiescent by regulating their entry to the cell cycle.
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U2 - 10.1016/j.ccr.2006.02.017
DO - 10.1016/j.ccr.2006.02.017
M3 - Article
C2 - 16530702
AN - SCOPUS:33644819269
SN - 1535-6108
VL - 9
SP - 175
EP - 187
JO - Cancer cell
JF - Cancer cell
IS - 3
ER -