MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages

Athar Aziz; Erinn Soucie; Sandrine Sarrazin; Michael H Sieweke

doi:10.1126/science.1176056

MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages

Science. 2009 Nov 6;326(5954):867-71. doi: 10.1126/science.1176056.

Authors

Athar Aziz¹, Erinn Soucie, Sandrine Sarrazin, Michael H Sieweke

Affiliation

¹ Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.

PMID: 19892988
DOI: 10.1126/science.1176056

Abstract

In metazoan organisms, terminal differentiation is generally tightly linked to cell cycle exit, whereas the undifferentiated state of pluripotent stem cells is associated with unlimited self-renewal. Here, we report that combined deficiency for the transcription factors MafB and c-Maf enables extended expansion of mature monocytes and macrophages in culture without loss of differentiated phenotype and function. Upon transplantation, the expanded cells are nontumorigenic and contribute to functional macrophage populations in vivo. Small hairpin RNA inactivation shows that continuous proliferation of MafB/c-Maf deficient macrophages requires concomitant up-regulation of two pluripotent stem cell-inducing factors, KLF4 and c-Myc. Our results indicate that MafB/c-MafB deficiency renders self-renewal compatible with terminal differentiation. It thus appears possible to amplify functional differentiated cells without malignant transformation or stem cell intermediates.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Cell Proliferation*
Cell Transformation, Neoplastic
Cells, Cultured
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / physiology
Macrophage Colony-Stimulating Factor / metabolism
Macrophage Colony-Stimulating Factor / pharmacology
Macrophages / cytology
Macrophages / physiology*
Macrophages / transplantation
MafB Transcription Factor / deficiency*
MafB Transcription Factor / genetics
MafB Transcription Factor / physiology
Mice
Mice, Knockout
Monocytes / cytology
Monocytes / physiology
Myeloid Progenitor Cells / cytology
Myeloid Progenitor Cells / physiology
Phagocytosis
Proto-Oncogene Proteins c-maf / deficiency*
Proto-Oncogene Proteins c-maf / genetics
Proto-Oncogene Proteins c-maf / physiology
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / physiology
Up-Regulation

Substances

Klf4 protein, mouse
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
Maf protein, mouse
MafB Transcription Factor
Mafb protein, mouse
Myc protein, mouse
Proto-Oncogene Proteins c-maf
Proto-Oncogene Proteins c-myc
Macrophage Colony-Stimulating Factor