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Published (Version of record)CC BY V4.0, Open Access
Published (Version of record)CC BY V4.0, Open
Journal article
Integrated time-series analysis and high-content CRISPR screening delineate the dynamics of macrophage immune regulation
Cell systems, Vol.16(8), pp.1-29
20/08/2025
PMID: 40782800
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Abstract
Macrophages are innate immune cells involved in host defense. Dissecting the regulatory landscape that enables their swift and specific response to pathogens, we performed time-series analysis of gene expression and chromatin accessibility in murine macrophages exposed to various immune stimuli, and we functionally evaluated gene knockouts at scale using a combined CROP-seq and CITE-seq assay. We identified new roles of transcription regulators such as Spi1/PU.1 and JAK-STAT pathway members in immune cell homeostasis and response to pathogens. Macrophage activity was modulated by splicing proteins SFPQ and SF3B1, histone acetyltransferase EP300, cohesin subunit SMC1A, and mediator complex proteins MED8 and MED14. We further observed crosstalk among immune signaling pathways and identified molecular drivers of pathogen-induced dynamics. In summary, this study establishes a time-resolved regulatory map of pathogen response in macrophages, and it describes a broadly applicable method for dissecting immune-regulatory programs through integrative time-series analysis and high-content CRISPR screening. A record of this paper’s transparent peer review process is included in the supplemental information.
Details
- Title
- Integrated time-series analysis and high-content CRISPR screening delineate the dynamics of macrophage immune regulation
- Creators
- Peter Traxler - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)Stephan Reichl - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)Lukas Folkman - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)Lisa Shaw - Medical University of ViennaVictoria Fife - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)Amelie Nemc - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)Djurdja Pasajlic - Medical University of ViennaAnna Kusienicka - Medical University of ViennaDaniele Barreca - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)Nikolaus Fortelny - CeMM Research Center for Molecular MedicineAndré F. Rendeiro - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)Florian Halbritter - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)Wolfgang Weninger - Medical University of ViennaThomas Decker - Max Perutz LabsMatthias Farlik - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)Christoph Bock - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Austria)
- Publication Details
- Cell systems, Vol.16(8), pp.1-29
- Publisher
- Elsevier Inc
- Grant note
- Austrian Science Fund (FWF): SFB F6102, SFB F7001 Austrian Academy of Sciences: IF_2015_36 European Union: 101001971
We thank the Biomedical Sequencing Facility at CeMM for assistance with next generation sequencing, Sophie Zahalka and Sylvia Knapp for providing RAW 264.7-Cas9 cells, Michael Riedelberger and Karl Kuchler for providing Candida albicans SC5314, and Alexander Lercher and Andreas Bergthaler for providing LCMV Clone 13. This study was co-funded by two Austrian Science Fund (FWF) Special Research Program grants (SFB F6102; SFB F7001). In addition, M.F. was supported by an Innovation Fund grant of the Austrian Academy of Sciences (IF_2015_36) and C.B. was supported by an ERC Consolidator Grant (grant agreement no. 101001971) of the European Union's Horizon 2020 research and innovation program.
- Identifiers
- 991013341085802368
- Copyright
- © 2025 The Author(s).
- Academic Unit
- Faculty of Science and Engineering
- Language
- English
- Resource Type
- Journal article