Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment

Yonit Lavin, Deborah Winter, Ronnie Blecher-Gonen, Eyal David, Hadas Keren-Shaul, Miriam Merad*, Steffen Jung, Ido Amit

*Corresponding author for this work

Research output: Contribution to journalArticle

890 Scopus citations

Abstract

Macrophages are critical for innate immune defense and also control organ homeostasis in a tissue-specific manner. They provide a fitting model to study the impact of ontogeny and microenvironment on chromatin state and whether chromatin modifications contribute to macrophage identity. Here, we profile the dynamics of four histone modifications across seven tissue-resident macrophage populations. We identify 12,743 macrophage-specific enhancers and establish that tissue-resident macrophages have distinct enhancer landscapes beyond what can be explained by developmental origin. Combining our enhancer catalog with gene expression profiles and open chromatin regions, we show that a combination of tissue- and lineage-specific transcription factors form the regulatory networks controlling chromatin specification in tissue-resident macrophages. The environment is capable of shaping the chromatin landscape of transplanted bone marrow precursors, and even differentiated macrophages can be reprogramed when transferred into a new microenvironment. These results provide a comprehensive view of macrophage regulatory landscape and highlight the importance of the microenvironment, along with pioneer factors in orchestrating identity and plasticity.

Original languageEnglish (US)
Pages (from-to)1312-1326
Number of pages15
JournalCell
Volume159
Issue number6
DOIs
StatePublished - Dec 4 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lavin, Y., Winter, D., Blecher-Gonen, R., David, E., Keren-Shaul, H., Merad, M., Jung, S., & Amit, I. (2014). Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell, 159(6), 1312-1326. https://doi.org/10.1016/j.cell.2014.11.018