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

doi:10.1016/j.cell.2014.11.018

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

Medicine, Rheumatology Division

Research output: Contribution to journal › Article › peer-review

1594 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 language	English (US)
Pages (from-to)	1312-1326
Number of pages	15
Journal	Cell
Volume	159
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2014.11.018
State	Published - Dec 4 2014

Funding

We thank members of the I.A., S.J., and M.M. labs for discussions. We thank Tali Wiesel and Genia Brodsky for artwork. Research in the I.A. lab is supported by the European Research Council (309788) and the Israeli Science Foundation (1782/11), The Human Frontiers Science Program, Career Development Award, and the Center for Excellence in Genome Science from the NHGRI 1P50HG006193. Research in the S.J. lab is supported by the Israeli Science Foundation (887/11), the European Research Council (340345), and the Deutsche Forschungsgemeinschaft (FOR1336). M.M. is supported by NIH R01CA154947A, NIHR01CA173861, NIHU01AI095611, and NIHR01AI104848. D.W. is grateful to the Azrieli Foundation for the Azrieli Fellowship award and EMBO for the Long-Term Fellowship. Y.L. is grateful for the MSTP training grant support.

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2014.11.018

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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.",

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AU - David, Eyal

AU - Keren-Shaul, Hadas

AU - Merad, Miriam

AU - Jung, Steffen

AU - Amit, Ido

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N2 - 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.

AB - 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.

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

Abstract

Funding

ASJC Scopus subject areas

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