Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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.
Details
Original language | English |
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Article number | aad5510 |
Journal | Science |
Volume | 351 |
Issue number | 6274 |
Publication status | Published - 12 Feb 2016 |
Peer-reviewed | Yes |
External IDs
PubMedCentral | PMC4811353 |
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Scopus | 84958191207 |
Keywords
Keywords
- Animals, Cell Differentiation/genetics, Cell Lineage/genetics, Cell Proliferation, Cells, Cultured, Down-Regulation, Embryonic Stem Cells/cytology, Enhancer Elements, Genetic/physiology, Gene Expression Regulation, Gene Regulatory Networks, Macrophages/cytology, MafB Transcription Factor/metabolism, Mice, Proto-Oncogene Proteins c-maf/metabolism, Single-Cell Analysis, Transcriptional Activation