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Conditional knockout mice demonstrate function of Klf5 as a myeloid transcription factor

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dc.contributor.authorShahrin, N.
dc.contributor.authorDiakiw, S.
dc.contributor.authorDent, L.
dc.contributor.authorBrown, A.
dc.contributor.authorD'Andrea, R.
dc.date.issued2016
dc.description.abstractKrüppel-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.
dc.description.statementofresponsibilityNur Hezrin Shahrin, Sonya Diakiw, Lindsay A. Dent, Anna L. Brown, and Richard J. D'Andrea
dc.identifier.citationBlood, 2016; 128(1):55-59
dc.identifier.doi10.1182/blood-2015-12-684514
dc.identifier.issn0006-4971
dc.identifier.issn1528-0020
dc.identifier.orcidDent, L. [0000-0002-3521-408X]
dc.identifier.orcidBrown, A. [0000-0002-9023-0138]
dc.identifier.urihttp://hdl.handle.net/2440/102075
dc.language.isoen
dc.publisherAmerican Society of Hematology
dc.rights© 2016 by The American Society of Hematology
dc.source.urihttps://doi.org/10.1182/blood-2015-12-684514
dc.subjectEosinophils
dc.subjectNeutrophils
dc.subjectMultipotent Stem Cells
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectMice
dc.subjectGene Expression Regulation
dc.subjectKruppel-Like Transcription Factors
dc.subjectGranulocyte-Macrophage Progenitor Cells
dc.subjectCD18 Antigens
dc.subjectIntegrin beta1
dc.titleConditional knockout mice demonstrate function of Klf5 as a myeloid transcription factor
dc.typeJournal article
pubs.publication-statusPublished

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