The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation

Mark W. Feinberg, Akm Khyrul Wara, Zhuoxiao Cao, Maria A. Lebedeva, Frank Rosenbauer, Hiromi Iwasaki, Hideyo Hirai, Jonathan P. Katz, Richard L. Haspel, Susan Gray, Koichi Akashi, Julie Segre, Klaus H. Kaestner, Daniel G. Tenen, Mukesh K. Jain

Research output: Contribution to journalArticle

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Abstract

Monocyte differentiation involves the participation of lineage-restricted transcription factors, although the mechanisms by which this process occurs are incompletely defined. Within the hematopoietic system, members of the Kruppel-like family of factors (KLFs) play essential roles in erythrocyte and T lymphocyte development. Here we show that KLF4/GKLF is expressed in a monocyte-restricted and stage-specific pattern during myelopoiesis and functions to promote monocyte differentiation. Overexpression of KLF4 in HL-60 cells confers the characteristics of mature monocytes. Conversely, KLF4 knockdown blocked phorbol ester-induced monocyte differentiation. Forced expression of KLF4 in primary common myeloid progenitors (CMPs) or hematopoietic stem cells (HSCs) induced exclusive monocyte differentiation in clonogenic assays, whereas KLF4 deficiency inhibited monocyte but increased granulocyte differentiation. Mechanistic studies demonstrate that KLF4 is a target gene of PU.1. Consistently, KLF4 can rescue PU.1-/- fetal liver cells along the monocytic lineage and can activate the monocytic-specific CD14 promoter. Thus, KLF4 is a critical regulator in the transcriptional network controlling monocyte differentiation.

Original languageEnglish
Pages (from-to)4138-4148
Number of pages11
JournalEMBO Journal
Volume26
Issue number18
DOIs
Publication statusPublished - Sep 19 2007

Fingerprint

Kruppel-Like Transcription Factors
T-cells
Phorbol Esters
Stem cells
Liver
Monocytes
Assays
Transcription Factors
Genes
Myeloid Progenitor Cells
Myelopoiesis
Hematopoietic System
Gene Regulatory Networks
HL-60 Cells
Hematopoietic Stem Cells
Granulocytes
Erythrocytes
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Feinberg, M. W., Wara, A. K., Cao, Z., Lebedeva, M. A., Rosenbauer, F., Iwasaki, H., ... Jain, M. K. (2007). The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation. EMBO Journal, 26(18), 4138-4148. https://doi.org/10.1038/sj.emboj.7601824

The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation. / Feinberg, Mark W.; Wara, Akm Khyrul; Cao, Zhuoxiao; Lebedeva, Maria A.; Rosenbauer, Frank; Iwasaki, Hiromi; Hirai, Hideyo; Katz, Jonathan P.; Haspel, Richard L.; Gray, Susan; Akashi, Koichi; Segre, Julie; Kaestner, Klaus H.; Tenen, Daniel G.; Jain, Mukesh K.

In: EMBO Journal, Vol. 26, No. 18, 19.09.2007, p. 4138-4148.

Research output: Contribution to journalArticle

Feinberg, MW, Wara, AK, Cao, Z, Lebedeva, MA, Rosenbauer, F, Iwasaki, H, Hirai, H, Katz, JP, Haspel, RL, Gray, S, Akashi, K, Segre, J, Kaestner, KH, Tenen, DG & Jain, MK 2007, 'The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation', EMBO Journal, vol. 26, no. 18, pp. 4138-4148. https://doi.org/10.1038/sj.emboj.7601824
Feinberg MW, Wara AK, Cao Z, Lebedeva MA, Rosenbauer F, Iwasaki H et al. The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation. EMBO Journal. 2007 Sep 19;26(18):4138-4148. https://doi.org/10.1038/sj.emboj.7601824
Feinberg, Mark W. ; Wara, Akm Khyrul ; Cao, Zhuoxiao ; Lebedeva, Maria A. ; Rosenbauer, Frank ; Iwasaki, Hiromi ; Hirai, Hideyo ; Katz, Jonathan P. ; Haspel, Richard L. ; Gray, Susan ; Akashi, Koichi ; Segre, Julie ; Kaestner, Klaus H. ; Tenen, Daniel G. ; Jain, Mukesh K. / The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation. In: EMBO Journal. 2007 ; Vol. 26, No. 18. pp. 4138-4148.
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