Alveolar macrophages (AMs), the resident macrophages of the lung, can be expanded ex vivo to generate large numbers of cells but show culture adaptations related to epigenetic and transcriptional changes. After transplantation into the lungs of mice, however, culture-expanded AMs lose these adaptations, fully restore in vivo identity and functionally reconstitute the AM pool.
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References
Soucie, E. L. et al. Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells. Science 351, aad5510 (2016). The study shows that AMs can access a self-renewal gene network and can be expanded in culture.
Gosselin, D. et al. An environment-dependent transcriptional network specifies human microglia identity. Science 356, eaal3222 (2017). The study shows substantial loss of microglia-specific gene expression in culture.
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Guilliams, M. & Svedberg, F. R. Does tissue imprinting restrict macrophage plasticity? Nat. Immunol. 22, 118–127 (2021). A Review article reflecting on the role of the niche environment and epigenetic imprinting on AM identity and plasticity.
de Laval, B. et al. C/EBPβ-dependent epigenetic memory induces trained immunity in hematopoietic stem cells. Cell Stem Cell 26, 793 (2020). In contrast to the loss of epigenetic changes of cultured AM in vivo, this study shows that LPS-induced epigenetic changes in hematopoietic stem cells persist throughout transplantation.
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This is a summary of: Subramanian, S. et al. Long-term culture-expanded alveolar macrophages restore their full epigenetic identity after transfer in vivo. Nat. Immunol. https://doi.org/10.1038/s41590-022-01146-w (2022)
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Culture amplified macrophages reassume identity and function in vivo. Nat Immunol 23, 358–359 (2022). https://doi.org/10.1038/s41590-022-01151-z
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DOI: https://doi.org/10.1038/s41590-022-01151-z
