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Long-term culture-expanded alveolar macrophages restore their full epigenetic identity after transfer in vivo
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Abstract
Alveolar macrophages (AMs) are lung tissue-resident macrophages that can be expanded in culture, but it is unknown to what extent culture affects their in vivo identity. Here we show that mouse long-term ex vivo expanded AMs (exAMs) maintained a core AM gene expression program, but showed culture adaptations related to adhesion, metabolism and proliferation. Upon transplantation into the lung, exAMs reacquired full transcriptional and epigenetic AM identity, even after several months in culture and could self-maintain long-term in the alveolar niche. Changes in open chromatin regions observed in culture were fully reversible in transplanted exAMs and resulted in a gene expression profile indistinguishable from resident AMs. Our results indicate that long-term proliferation of AMs in culture did not compromise cellular identity in vivo. The robustness of exAM identity provides new opportunities for mechanistic analysis and highlights the therapeutic potential of exAMs.
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“New protocols are developing to ensure that transplanted macrophages retain their desired epigenetic and transcriptional profiles.154”
From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [154]
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Metadata
- Authors
- Subramanian, S., Busch, C. J.-L., Molawi, K., Geirsdottir, L., Maurizio, J., Vargas Aguilar, S., Belahbib, H., Gimenez, G., Yuda, R. A. A., Burkon, M., Favret, J., Gholamhosseinian Najjar, S., de Laval, B., Kandalla, P. K., Sarrazin, S., Alexopoulou, L., & Sieweke, M. H.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Center for Regenerative Therapies Dresden (DE)
- Inovarion (France) (FR)
- Corresponding author
- Sieweke, Michael H.
- ORCID
- Venue
- Nature Immunology
- Published
- 2022-02-24
- Volume
- 23
- Issue
- 3
- Pages
- 458-468
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W4213453160
- Cited by
- 103
- References
- 57
- Citations by year
- 2026: 23 · 2025: 29 · 2024: 22 · 2023: 21 · 2022: 8
- FWCI
- 7.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Immunology (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Qucosa (Saxon State and University Library Dresden) (submittedVersion, other-oa)
- Funders
- Aix-Marseille Université
- European Commission (HORIZON2020)
- Agence Nationale de la Recherche (ANR-17-CE15-0007, ANR-18-CE12-0019, ANR18, ANR-17)
- Institut National de la Santé et de la Recherche Médicale
- Technische Universität Dresden
- Fondation ARC pour la Recherche sur le Cancer (PGA1 RF20170205515)
- Centre National de la Recherche Scientifique
- Zentrum für Regenerative Therapien Dresden
- Stiftung Charité
- H2020 European Research Council (695093)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- alveolar macrophages, macrophage identity, epigenetic reprogramming, chromatin accessibility, open chromatin, macrophage transplantation, macrophage proliferation, macrophage metabolism, macrophage adhesion, transcriptional programs
- MeSH terms
- Animals, Chromatin, Lung, Macrophages, Alveolar, Epigenesis, Genetic, Mice, Epigenomics
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