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Studying tissue macrophages in vitro: are iPSC-derived cells the answer?

Nature Reviews Immunologyvolume 18pages716725 (2018) | Download Citation


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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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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  1. Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), BIOPOLIS, Singapore, Singapore

    • Christopher Z. W. Lee
    • , Tatsuya Kozaki
    •  & Florent Ginhoux
  2. Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, 280 South Chongqing Road, Shanghai, China

    • Florent Ginhoux


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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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The authors declare no competing interests.

Corresponding author

Correspondence to Florent Ginhoux.



(AGM). The region of the embryonic mesoderm where the first intra-embryonic haematopoietic progenitors arise.

Embryoid bodies

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

(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.


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.


A mouse model that allows for isolation of only ribosome-associated mRNA, eliminating the possibility of contaminating exogenous mRNA.

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