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- 조회81
Cell Syst., February 11, 2025 | https://doi.org/10.1016/j.cels.2025.101171
Macrophage memory emerges from coordinated transcription factor and chromatin dynamics
Andrew G. Wang 1,2,6, Minjun Son 1,3,6, Aleksandr Gorin 4, Emma Kenna 1, Abinash Padhi 1, Bijentimala Keisham 1, Adam Schauer 3, Alexander Hoffmann 5, Savaş Tay 1,7,*
1Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA
2Medical Scientist Training Program, University of Chicago, Chicago, IL 60637, USA
3Chan Zuckerberg Biohub Chicago, Chicago, IL, USA
4Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles, Los Angeles, CA 90095, USA
5Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA
6These authors contributed equally
7Lead contact
2Medical Scientist Training Program, University of Chicago, Chicago, IL 60637, USA
3Chan Zuckerberg Biohub Chicago, Chicago, IL, USA
4Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles, Los Angeles, CA 90095, USA
5Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA
6These authors contributed equally
7Lead contact
*Corresponding author: correspondence to Savaş Tay
Abstract
Cells of the immune system operate in dynamic microenvironments where the timing, concentration, and order of signaling molecules constantly change. Despite this complexity, immune cells manage to communicate accurately and control inflammation and infection. It is unclear how these dynamic signals are encoded and decoded and if individual cells retain the memory of past exposure to inflammatory molecules. Here, we use live-cell analysis, ATAC sequencing, and an in vivo model of sepsis to show that sequential inflammatory signals induce memory in individual macrophages through reprogramming the nuclear factor κB (NF-κB) network and the chromatin accessibility landscape. We use transcriptomic profiling and deep learning to show that transcription factor and chromatin dynamics coordinate fine-tuned macrophage responses to new inflammatory signals. This work demonstrates how macrophages retain the memory of previous signals despite single-cell variability and elucidates the mechanisms of signal-induced memory in dynamic inflammatory conditions like sepsis.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-25)
- 국외 연구진
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