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Type: Journal article
Title: Conditional knockout mice demonstrate function of Klf5 as a myeloid transcription factor
Author: Shahrin, N.
Diakiw, S.
Dent, L.
Brown, A.
D'Andrea, R.
Citation: Blood, 2016; 128(1):55-59
Publisher: American Society of Hematology
Issue Date: 2016
ISSN: 0006-4971
Statement of
Nur Hezrin Shahrin, Sonya Diakiw, Lindsay A. Dent, Anna L. Brown, and Richard J. D'Andrea
Abstract: Krüppel-like factor 5 (Klf5) encodes a zinc-finger transcription factor and has been reported to be a direct target of C/EBPα, a master transcription factor critical for formation of granulocyte-macrophage progenitors (GMP) and leukemic GMP. Using an in vivo hematopoietic-specific gene ablation model, we demonstrate that loss of Klf5 function leads to a progressive increase in peripheral white blood cells, associated with increasing splenomegaly. Long-term hematopoietic stem cells (HSCs), short-term HSCs (ST-HSCs), and multipotent progenitors (MPPs) were all significantly reduced in Klf5(Δ/Δ) mice, and knockdown of KLF5 in human CD34(+) cells suppressed colony-forming potential. ST-HSCs, MPPs, and total numbers of committed progenitors were increased in the spleen of Klf5(Δ/Δ) mice, and reduced β1- and β2-integrin expression on hematopoietic progenitors suggests that increased splenic hematopoiesis results from increased stem and progenitor mobilization. Klf5(Δ/Δ) mice show a significant reduction in the fraction of Gr1(+)Mac1(+) cells (neutrophils) in peripheral blood and bone marrow and increased frequency of eosinophils in the peripheral blood, bone marrow, and lung. Thus, these studies demonstrate dual functions of Klf5 in regulating hematopoietic stem and progenitor proliferation and localization in the bone marrow, as well as lineage choice after GMP, promoting increased neutrophil output at the expense of eosinophil production.
Keywords: Eosinophils; Neutrophils; Multipotent Stem Cells; Animals; Mice, Knockout; Mice; Gene Expression Regulation; Kruppel-Like Transcription Factors; Granulocyte-Macrophage Progenitor Cells; CD18 Antigens; Integrin beta1
Rights: © 2016 by The American Society of Hematology
RMID: 0030050069
DOI: 10.1182/blood-2015-12-684514
Appears in Collections:Molecular and Biomedical Science publications

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