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

Aziz, A, Soucie, E, Sarrazin, S and Sieweke, MH 2009, 'MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages' , Science, 326 (5954) , pp. 867-871.

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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.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Schools > School of Environment and Life Sciences
Journal or Publication Title: Science
Publisher: HIghWire Press
Refereed: Yes
ISSN: 0036-8075
Related URLs:
Depositing User: S Rafiq
Date Deposited: 23 Jun 2014 17:00
Last Modified: 30 Nov 2015 23:58

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