Abstract
Macrophages are immune cells with important roles in tissue homeostasis, inflammation and pathologies. Hence, macrophage populations represent promising targets for modern medicine. Exploiting the potential of macrophage-targeted therapies will require a thorough understanding of the mechanisms controlling their development, specialization and maintenance throughout their lifespan. Macrophages have been studied in vitro for many years, but recent advances in the field of macrophage biology have called into question the validity of traditional approaches. New models, such as recent innovations in generating macrophages from induced pluripotent stem cells (iPSCs), must take into account the impact of heterogeneity in the origin and tissue-specific functions of macrophages. Here, we discuss these protocols and argue for a better understanding of the type of macrophages made in vitro; we also encourage recognition of the importance of tissue identity of macrophages, which cannot be recapitulated by cytokine-dependent protocols. We suggest that a two-step model — in which iPSC-derived macrophages are first generated based on their ontogeny and then conditioned by their tissue-specific environment — offers immense potential for generating biologically relevant macrophages for future studies.
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Change history
30 August 2018
In the original Figure 1, an arrow was mistakenly added between the fetal liver monocytes and the short-term and long-term HSCs. This arrow has now been removed.
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Acknowledgements
F.G., T.K. and C.Z.W.L. are supported by Singapore Immunology Network (SIgN) core funding. F.G. is an European Molecular Biology Organization (EMBO) YIP awardee and supported by the Singapore National Research Foundation Senior Investigatorship (NRFI) NRF2016NRF-NRFI001-02. The authors thank L. Robinson of Insight Editing London for assistance with editing.
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F.G. and C.Z.W.L. contributed to researching data, discussing content and writing and editing the article. T.K. contributed to researching data and writing the article.
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Glossary
- Aorta-gonad-mesonephros
-
(AGM). The region of the embryonic mesoderm where the first intra-embryonic haematopoietic progenitors arise.
- Embryoid bodies
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These structures form from the spontaneous aggregation of pluripotent stem cells into a 3D structure. They are often used as a method to initiate germ layer formation.
- Endothelial-to-haematopoietic transition
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(EHT). The process by which endothelial cells bud off and acquire haematopoietic identity.
- Erythomyeloid progenitors
-
(EMPs). Haematopoietic progenitors with only erythroblast and/or erythrocyte and myeloid cell potential.
- Feeder-free
-
A method of culturing pluripotent stem cells that does not require co-culturing with fibroblasts to maintain pluripotency.
- Haemangioblasts/haemogenic endothelial cells
-
Multipotent stem cells that can differentiate into both endothelial and haematopoietic cells.
- Primitive streak
-
An embryonic structure from which germ layer specification begins.
- RiboTag
-
A mouse model that allows for isolation of only ribosome-associated mRNA, eliminating the possibility of contaminating exogenous mRNA.
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Lee, C.Z.W., Kozaki, T. & Ginhoux, F. Studying tissue macrophages in vitro: are iPSC-derived cells the answer?. Nat Rev Immunol 18, 716–725 (2018). https://doi.org/10.1038/s41577-018-0054-y
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DOI: https://doi.org/10.1038/s41577-018-0054-y
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