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Regulation of monocyte differentiation by specific signaling modules and associated transcription factor networks

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Abstract

Monocyte/macrophages are important players in orchestrating the immune response as well as connecting innate and adaptive immunity. Myelopoiesis and monopoiesis are characterized by the interplay between expansion of stem/progenitor cells and progression towards further developed (myelo)monocytic phenotypes. In response to a variety of differentiation-inducing stimuli, various prominent signaling pathways are activated. Subsequently, specific transcription factors are induced, regulating cell proliferation and maturation. This review article focuses on the integration of signaling modules and transcriptional networks involved in the determination of monocytic differentiation.

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Abbreviations

1,25(OH)2D3:

1,25-dihydroxy vitamin D3

4HT:

4-hydroxytamoxifen

AML:

Acute myeloid leukemia

AP:

Activator protein

ATF:

Activating transcription factor

ATRA:

All-trans retinoic acid

Bcr/Abl:

Breakpoint cluster region/Abelson murine leukemia viral oncogene homolog fusion protein

BLIMP:

B lymphocyte-induced maturation protein

Bmi:

Homolog of B cell-specific Moloney murine leukemia virus integration site

bZIP:

Basic leucine zipper

CIITA:

Class II major histocompatibility complex transactivator

CBP:

CREB binding protein

CD:

Cluster of differentiation

CDDO:

2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid

CDK:

Cyclin-dependent kinase

C/EBP:

CCAAT/enhancer binding protein

CLP:

Common lymphoid progenitor

CML:

Chronic myelogenous leukemia

CMP:

Common myeloid progenitor

c-Myc:

Avian myelocytomatosis viral oncogene homolog

Cox:

Cyclooxygenase

c-Rel:

Avian reticuloendotheliosis viral oncogene homolog

CREB:

CAMP response element-binding protein

CSF:

Colony-stimulating factor

CSFR:

CSF receptor

CXCL:

C-X-C-motif chemokine ligand

DAG:

Diacylgylcerol

DC:

Dendritic cell

EDAG:

Erythroid differentiation-associated gene

ER:

Estrogen receptor

ERK:

Extracellular signal-regulated kinase

Ets:

E26 transformation-specific

FAK:

Focal adhesion kinase

FcγR:

Fcγ receptor

FLT3:

Fms-like tyrosine kinase 3

FLT3L:

FLT3 ligand

Fos:

v-Fos murine osteosarcoma viral oncogene homolog

FoxO:

Forkhead box protein O

Fra:

Fos-related antigen

GABP:

GA-binding protein

GATA:

GATA-binding factor

G-CSF:

Granulocyte CSF

Gfi:

Growth factor-independent

GM-CSF:

Granulocyte/macrophage CSF

GMP:

Granulocyte/monocyte progenitor

GPCR:

G protein-coupled receptor

GSK:

Glycogen synthase kinase

HIV:

Human immunodeficiency virus

Hox:

Homeobox

HPK:

Hematopoietic progenitor kinase

HSC:

Hematopoietic stem cell

IFN:

Interferon

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

IRF:

Interferon regulatory factor

JAK:

Janus kinase

JDP:

Jun dimerization protein

JNK:

c-Jun N-terminal kinase

kd:

Knock down

KLF:

Krueppel-like factor

ko:

Knock out

LAP:

Liver-enriched activating protein

LIF:

Leukemia inhibitory factor

LIP:

Liver-enriched inhibitory protein

LPS:

Lipopolysaccharide

Ly6C:

Lymphocyte antigen 6 complex locus C

Maf:

Musculoaponeurotic fibrosarcoma oncogene homolog

MAPK:

Mitogen-activated protein kinase

MAP3K:

MAPK kinase kinase

M-CSF:

Macrophage-colony stimulating factor

MDP:

Monocyte/macrophage and dendritic cell progenitor

MEK:

MAPK/ERK kinase

MEP:

Megakaryocyte-erythroid progenitor

METS:

Mitogenic Ets transcriptional suppressor

MIP:

Macrophage inflammatory protein

MKK:

MAPK kinase

MLL:

Mixed-lineage leukemia

MPP:

Multipotent progenitor

mTOR:

Mammalian target of rapamycin

NF-κB:

Nuclear factor κ-light-chain-enhancer of activated B cells

NOD:

Non-obese diabetic

Numb:

Homolog of Drosophila Numb

OSM:

Oncostatin M

Pax:

Paired box protein

PI3K:

Phosphoinositide-3-kinase

PIP3:

Phosphoinositide-3,4,5-trisphosphate

PKB:

Protein kinase B

PKC:

Protein kinase C

PMA:

Phorbol-12-myristate 13-acetate

PTP:

Protein tyrosine phosphatase

PU.1:

Purine-rich box 1

PU.1/ER:

PU.1/estrogen receptor fusion protein

Pyk:

Proline-rich tyrosine kinase

RA:

Retinoic acid

Raf:

Rapidly accelerated fibrosarcoma

RAR:

Retinoic acid receptor

Ras:

Rat sarcoma

Rb:

Retinoblastoma protein

Rheb:

Ras homolog enriched in brain

RSK:

90-kDa ribosomal protein S6 kinase

RTK:

Receptor tyrosine kinase

RXR:

Retinoic X receptor

SCF:

Stem cell factor

SCID:

Severe combined immunodeficiency

Shp:

Src homology 2 domain-containing protein tyrosine phosphatase

SFK:

Src family kinase

sRAGE:

Soluble receptor for advanced glycation end products

Src:

v-Src avian sarcoma viral oncogene homolog

STAT:

Signal transducer and activator of transcription

TGF:

Transforming growth factor

THOC:

THO complex

TNF:

Tumor necrosis factor

TSC:

Tuberous sclerosis protein

Tyk:

Tyrosine kinase

UA:

Ursolic acid

VDR:

Vitamin D receptor

VDRE:

Vitamin D responsive element

Vit:

Vitamin

wt:

Wild type

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Acknowledgements

We thank Kerstin Püllmann for helpful discussions, Sharon Page for critical reading of the manuscript, and apologize to all authors/working groups whose work has not been considered for this review. This work was supported by the Stiftung für Pathobiochemie und Molekulare Diagnostik der Deutschen Gesellschaft für Klinische Chemie und Laboratoriumsmedizin (DGKL) and by the Deutsche Forschungsgemeinschaft (DFG; SFB 566).

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  1. Institute of Clinical Chemistry, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany

    René Huber, Daniel Pietsch, Johannes Günther, Bastian Welz, Nico Vogt & Korbinian Brand

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  1. René Huber
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Huber, R., Pietsch, D., Günther, J. et al. Regulation of monocyte differentiation by specific signaling modules and associated transcription factor networks. Cell. Mol. Life Sci. 71, 63–92 (2014). https://doi.org/10.1007/s00018-013-1322-4

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