Long-term culture-expanded alveolar macrophages restore their full epigenetic identity after transfer in vivo

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 ad...

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Bibliographic Details
Published in:	Nature immunology Vol. 23; no. 3; pp. 458 - 468
Main Authors:	Subramanian, Sethuraman, Busch, Clara Jana-Lui, Molawi, Kaaweh, Geirsdottir, Laufey, Maurizio, Julien, Vargas Aguilar, Stephanie, Belahbib, Hassiba, Gimenez, Gregory, Yuda, Ridzky Anis Advent, Burkon, Michaela, Favret, Jérémy, Gholamhosseinian Najjar, Sara, de Laval, Bérengère, Kandalla, Prashanth Kumar, Sarrazin, Sandrine, Alexopoulou, Lena, Sieweke, Michael H.
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-03-2022 Nature Publishing Group
Subjects:	631/1647/514/2254 631/250/2504/342/1927 631/250/262 Adaptation Alveoli Animals Biomedical and Life Sciences Biomedicine Cell culture Chromatin Chromatin - metabolism Epigenesis, Genetic Epigenetics Epigenomics Gene expression Immunology Infectious Diseases Life Sciences Lung - metabolism Macrophages Macrophages, Alveolar - metabolism Mice technical-report Transcription
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Summary:	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. Sieweke and colleagues show that alveolar macrophages maintain a core gene expression program even after several months in culture and reacquire full transcriptional and epigenetic identity after transplantation into the lung.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1529-2908 1529-2916
DOI:	10.1038/s41590-022-01146-w