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

doi:10.1038/sj.emboj.7601824

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 journal › Article › peer-review

166 Citations (Scopus)

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 language	English
Pages (from-to)	4138-4148
Number of pages	11
Journal	EMBO Journal
Volume	26
Issue number	18
DOIs	https://doi.org/10.1038/sj.emboj.7601824
Publication status	Published - Sept 19 2007
Externally published	Yes

All Science Journal Classification (ASJC) codes

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

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10.1038/sj.emboj.7601824

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title = "The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation",

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.",

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

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T1 - The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation

AU - Feinberg, Mark W.

AU - Wara, Akm Khyrul

AU - Cao, Zhuoxiao

AU - Lebedeva, Maria A.

AU - Rosenbauer, Frank

AU - Iwasaki, Hiromi

AU - Hirai, Hideyo

AU - Katz, Jonathan P.

AU - Haspel, Richard L.

AU - Gray, Susan

AU - Akashi, Koichi

AU - Segre, Julie

AU - Kaestner, Klaus H.

AU - Tenen, Daniel G.

AU - Jain, Mukesh K.

PY - 2007/9/19

Y1 - 2007/9/19

N2 - 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.

AB - 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.

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

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