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

Autor: Subramanian S; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France.; Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft (MDC), Berlin, Germany., Busch CJ; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Molawi K; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France.; Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft (MDC), Berlin, Germany., Geirsdottir L; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Maurizio J; Inovarion, Paris, France., Vargas Aguilar S; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France.; Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft (MDC), Berlin, Germany., Belahbib H; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Gimenez G; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Yuda RAA; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Burkon M; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Favret J; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Gholamhosseinian Najjar S; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., de Laval B; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Kandalla PK; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany., Sarrazin S; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Alexopoulou L; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Sieweke MH; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany. michael.sieweke@tu-dresden.de.; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France. michael.sieweke@tu-dresden.de.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2022 Mar; Vol. 23 (3), pp. 458-468. Date of Electronic Publication: 2022 Feb 24.
DOI: 10.1038/s41590-022-01146-w
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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