title: Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment.
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 reprogrammed 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.
authors.affiliation: Department of Oncological Sciences, Immunology Institute and the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Yonit
authors.initials: Y
authors.lastname: Lavin
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Deborah
authors.initials: D
authors.lastname: Winter
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Blecher-Gonen
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Keren-Shaul
authors.affiliation: Department of Oncological Sciences, Immunology Institute and the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: miriam.merad@mssm.edu.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: s.jung@weizmann.ac.il.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: ido.amit@weizmann.ac.il.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D005260:Female; D042421:Histone Code; D006657:Histones / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D009928:Organ Specificity; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors