MafB/c-Maf Deficiency Enables Self-Renewal of Differentiated Functional Macrophages

Athar Aziz,^1,2,3,* Erinn Soucie,^1,2,3,* Sandrine Sarrazin,^1,2,3 Michael H. Sieweke^1,2,3,

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.

¹ Centre d’Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.
² Institut National de la Santé et de la Recherche Médicale (INSERM), U631, Marseille, France.
³ Centre National de la Recherche Scientifique (CNRS), UMR6102, Marseille, France.

To whom correspondence should be addressed. E-mail: sieweke{at}ciml.univ-mrs.fr

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