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Science. 2016 Feb 12;351(6274):aad5510. doi: 10.1126/science.aad5510. Epub 2016 Jan 21.

Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells.

Author information

1
Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Centre de Recherche en Cancerologie de Marseille, INSERM (U1068), CNRS (U7258), Université Aix-Marseille (UM105), Marseille, France. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu.
2
Department of Pathology, Stanford University, Stanford, CA 94305-5324, USA.
3
Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
4
Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft, 10 Robert-Rössle-Strasse, 13125 Berlin, Germany.
5
Broad Institute of Harvard University and MIT, Cambridge, MA 02142, USA.
6
Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, 1919 Route de Mende, 34293 Montpellier, France.
7
Centre de Recherche en Cancerologie de Marseille, INSERM (U1068), CNRS (U7258), Université Aix-Marseille (UM105), Marseille, France.
8
Department of Pathology, Stanford University, Stanford, CA 94305-5324, USA. Department of Genetics, Stanford University, Stanford, CA 94305, USA. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu.
9
Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft, 10 Robert-Rössle-Strasse, 13125 Berlin, Germany. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu.

Abstract

Differentiated macrophages can self-renew in tissues and expand long term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network that controls self-renewal. Single-cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells.

PMID:
26797145
PMCID:
PMC4811353
DOI:
10.1126/science.aad5510
[Indexed for MEDLINE]
Free PMC Article

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