Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

OPINION

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

Nature Reviews Immunology volume 18, pages 716–725 (2018)Cite this article

Subjects

A Publisher Correction to this article was published on 30 August 2018

This article has been updated

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Ontogenetic map of macrophage development based on pluripotent stem cells and mouse models.
Fig. 2: Evolving models for generating macrophages in vitro.
Fig. 3: Proposed models for generating biologically relevant macrophages.

Similar content being viewed by others

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.

References

  1. Gordon, S. & Plüddemann, A. Tissue macrophages: heterogeneity and functions. BMC Biol. 15, 53 (2017).

    Article  Google Scholar 

  2. Gosselin, D. et al. An environment-dependent transcriptional network specifies human microglia identity. Science 356, eaal3222 (2017).

    Article  Google Scholar 

  3. Sanz, E. et al. Cell-type-specific isolation of ribosome-associated mRNA from complex tissues. Proc. Natl Acad. Sci. USA 106, 13939–13944 (2009).

    Article  CAS  Google Scholar 

  4. van Furth, R. et al. The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull. World Health Organ. 46, 845–852 (1972).

    PubMed  PubMed Central  Google Scholar 

  5. Ginhoux, F. & Guilliams, M. Tissue-resident macrophage ontogeny and homeostasis. Immunity 44, 439–449 (2016).

    Article  CAS  Google Scholar 

  6. Ginhoux, F. et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841–845 (2010).

    Article  CAS  Google Scholar 

  7. Schulz, C. et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336, 86–90 (2012).

    Article  CAS  Google Scholar 

  8. Hoeffel, G. et al. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J. Exp. Med. 209, 1167–1181 (2012).

    Article  CAS  Google Scholar 

  9. Hoeffel, G. et al. C-Myb+ erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity 42, 655–678 (2015).

    Article  Google Scholar 

  10. Palis, J. & Yoder, M. C. Yolk-sac hematopoiesis: the first blood cells of mouse and man. Exp. Hematol. 29, 927–936 (2001).

    Article  CAS  Google Scholar 

  11. Bertrand, J. Y. et al. Definitive hematopoiesis initiates through a committed erythromyeloid progenitor in the zebrafish embryo. Development 134, 4147–4156 (2007).

    Article  CAS  Google Scholar 

  12. Gomea, P. E. et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature 518, 547–551 (2015).

    Article  Google Scholar 

  13. Cumano, A. Dieterlen-Lievre, F & Godin, l. Lymphoid potential, probed before circulation in mouse, is restricted to cadual intraembryonic splanchnopleura. Cell 86, 907–916 (1996).

    Article  Google Scholar 

  14. Medvinsky, A. & Dzierzak, E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 86, 897–906 (1996).

    Article  CAS  Google Scholar 

  15. Tavian, M., Robin, C., Coulombel. L. & Péault, B. The human embryo, but not its yolk sac, generates lympho-myeloid stem cells: mapping multipotent hematopoietic cell fate in intraembryonic mesoderm. Immunity 15, 487–495 (2001).

    Article  CAS  Google Scholar 

  16. Rybtsov, S., Ivanovs, A., Zhao, S. & Medvinsky, A. Concealed expansion of immature precursors underpins acute burst of adult HSC activity in foetal liver. Development 143, 1284–1289 (2016).

    Article  CAS  Google Scholar 

  17. Kumaravelu, P. et al. Quantitative developmental anatomy of definitive haematopoietic stem cells/long-term repopulating units (HSC/RUs): role of the aorta-gonad-mesonephros (AGM) region and the yolk sac in colonisation of the mouse embryonic liver. Development 129, 4891–4899 (2002).

    CAS  PubMed  Google Scholar 

  18. Hulsmans, M. et al. Macrophages facilitate electrical conduction in the heart. Cell 169, 510–522 (2017).

    Article  CAS  Google Scholar 

  19. Parkhurst, C. et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155, 1596–1609 (2013).

    Article  CAS  Google Scholar 

  20. Soares, M. P. & Hamza, I. Macrophages and iron metabolism. Immunity 44, 492–504 (2016).

    Article  CAS  Google Scholar 

  21. Gautier, E. L. et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat. Immunol. 13, 1118–11128 (2012).

    Article  CAS  Google Scholar 

  22. Lavin, Y. et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159, 1312–1326 (2014).

    Article  CAS  Google Scholar 

  23. Gosselin, D. et al. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159, 1327–1340 (2014).

    Article  CAS  Google Scholar 

  24. Guilliams, M. & Scott, C. L. Does niche competition determine the origin of tissue-resident macrophages? Nat. Rev. Immunol. 17, 451–460 (2017).

    Article  CAS  Google Scholar 

  25. Buttgereit, A. et al. Sall1 is a transcriptional regulator defining microglia identity and function. Nat. Immunol. 17, 1397–1406 (2016).

    Article  CAS  Google Scholar 

  26. Schneider, C. et al. Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat. Immunol. 15, 1026–1037 (2014).

    Article  CAS  Google Scholar 

  27. Nakamura, A. et al. Transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function. J. Exp. Med. 210, 2191–2204 (2013).

    Article  CAS  Google Scholar 

  28. Hacker, C. et al. Transcriptional profiling identifies Id2 function in dendritic cell development. Nat. Immunol. 4, 380–386 (2003).

    Article  CAS  Google Scholar 

  29. Fainaru, O. et al. Runx3 regulates mouse TGF-β-mediated dendritic cell function and its absence results in airway inflammation. EMBO J. 23, 969–979 (2004).

    Article  CAS  Google Scholar 

  30. Mass, E. et al. Specification of tissue-resident macrophages during organogenesis. Science 353, 6304 (2016).

    Article  Google Scholar 

  31. Martinez, F. O. & Gordon, S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 6, 13 (2014).

    Article  Google Scholar 

  32. Hagemeyer, N. et al. Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation. EMBO J. 35, 1730–1744 (2016).

    Article  CAS  Google Scholar 

  33. Ginhoux, F., Schultze, J. L., Murray, P. J., Ochando, J. & Biswas, S. K. New insights into the multidimensional concept of macrophage ontogeny, activation and function. Nat. Immunol. 17, 34–40 (2016).

    Article  CAS  Google Scholar 

  34. Gaelle, N. et al. A primary human macrophage-enteroid co-culture model to investigate muscosal gut physiology and host-pathogen interactions. Sci. Rep. 7, 45270 (2017).

    Article  Google Scholar 

  35. Linde, N., Gutschalk, C. M., Hoffmann, C., Yilmaz, D. & Mueller, M. M. Integrating macrophages into organotypic co-cultures: a 3D in vitro model to study tumor-associated macrophages. PLOS ONE 7, e40058 (2012).

    Article  CAS  Google Scholar 

  36. Keller, G., Kennedy, M., Papayannopoulou, T. & Wiles, M. V. Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol. Cell. Biol. 13, 473–486 (1993).

    Article  CAS  Google Scholar 

  37. van Wilgenburg, B., Browne, C., Vowles, J. & Cowley, S. A. Efficient, long term production of monocyte-derived macrophages from human pluripotent stem cells under partly-defined and fully-defined conditions. PLOS ONE 8, e71098 (2013).

    Article  Google Scholar 

  38. Lachmann, N. et al. Large-scale hematopoietic differentiation of human induced pluripotent stem cells provides granulocytes or macrophages for cell replacement therapies. Stem Cell Rep. 4, 282–296 (2015).

    Article  CAS  Google Scholar 

  39. Muffat, J. et al. Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat. Med. 22, 1358–1367 (2016).

    Article  CAS  Google Scholar 

  40. Amos, P. J. et al. Modulation of hematopoietic lineage specification impacts TREM2 expression in microglia-like cells derived from human stem cells. ASN Neuro. 9, 1759091417716610 (2017).

    Article  Google Scholar 

  41. Pandya, H. et al. Differentiation of human and murine induced pluripotent stem cells to microglia-like cells. Nat. Neurosci. 20, 753–759 (2017).

    Article  CAS  Google Scholar 

  42. Takata, K. et al. Induced-pluripotent-stem-cell-derived primitive macrophages provide a platform for modeling tissue-resident macrophage differentiation and function. Immunity 47, 183–198.e6 (2017).

    Article  CAS  Google Scholar 

  43. Abud, E. M. et al. iPSC-derived human microglia-like cells to study neurological diseases. Neuron 94, 278–293 (2017).

    Article  CAS  Google Scholar 

  44. Douvaras, P. et al. Directed differentiation of human pluripotent stem cells to microglia. Stem Cell Rep. 8, 1516–1524 (2017).

    Article  CAS  Google Scholar 

  45. Hoeffel, G. & Ginhoux, F. Ontogeny of tissue-resident macrophages. Front. Immunol. 6, 486 (2015).

    Article  Google Scholar 

  46. Karlsson, K. R. et al. Homogeneous monocytes and macrophages from human embryonic stem cells following coculture-free differentiation in M-CSF and IL-3. Exp. Hematol. 36, 1167–1175 (2008).

    Article  CAS  Google Scholar 

  47. Klimchenko, O. et al. Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions. Blood 117, 3065–3075 (2011).

    Article  CAS  Google Scholar 

  48. Palis, J., Robertson, S., Kennedy, M., Wall, C. & Keller, G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 126, 5073–5084 (1999).

    CAS  PubMed  Google Scholar 

  49. Pearson, S., Sroczynska, P., Lacaud, G. & Kouskoff, V. The stepwise specification of embryonic stem cells to hematopoietic fate is driven by sequential exposure to Bmp4, activin A, bFGF and VEGF. Development 135, 1525–1535 (2008).

    Article  CAS  Google Scholar 

  50. Yu, P., Pan, G., Yu, J. & Thomson, J. A. FGF2 sustains NANOG and switches the outcome of BMP4 induced human embryonic stem cell differentiation. Cell Stem Cell 8, 326–334 (2011).

    Article  CAS  Google Scholar 

  51. Leung, A. et al. Uncoupling VEGFA functions in arteriogenesis and hematopoietic stem cell specification. Dev. Cell 24, 144–158 (2013).

    Article  Google Scholar 

  52. Conlon, F. L., Barth, K. S. & Robertson, E. J. A novel retrovirally induced embryonic lethal mutation in the mouse: assessment of the developmental fate of embryonic stem cells homozygous for the 413.d proviral integration. Development 111, 969–981 (1991).

    CAS  PubMed  Google Scholar 

  53. Blauwkamp, T. A., Nigam, S., Ardehali, R., Weissman, I. L. & Nusse, R. Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors. Nat. Commun. 3, 1070 (2012).

    Article  Google Scholar 

  54. Kumano, K. et al. Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells. Immunity 18, 699–711 (2003).

    Article  CAS  Google Scholar 

  55. Burns, C. E., Traver, D., Mayhall, E., Shepard, J. L. & Zou, L. I. Hematopoietic stem cell fate is established by the Notch-Runx pathway. Genes Dev. 19, 2331–2342 (2005).

    Article  CAS  Google Scholar 

  56. Metcalf, D. Hematopoietic cytokines. Blood 111, 485–491 (2008).

    Article  CAS  Google Scholar 

  57. Vanhee, S. et al. In vitro human embryonic stem cell hematopoiesis mimics MYB-independent yolk sac hematopoiesis. Haematologica 100, 157–166 (2015).

    Article  CAS  Google Scholar 

  58. Buchrieser, J., James, W. & Moore, M. D. Human induced pluripotent stem cell-derived macrophages share ontogeny with MYB-independent tissue-resident macrophages. Stem Cell Rep. 8, 334–345 (2017).

    Article  CAS  Google Scholar 

  59. Chen, M. J., Yokomizo, T., Zeigler, B. M., Dzierzak, E. & Speck, N. A. Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature 457, 887–891 (2009).

    Article  CAS  Google Scholar 

  60. Sturgeon, C. M., Ditadi, A., Awong, G., Kennedy, M. & Keller, G. Wnt signaling controls the specification of definitive and primitive hematopoiesis from human pluripotent stem cells. Nat. Biotechnol. 32, 554–561 (2014).

    Article  CAS  Google Scholar 

  61. Ng, E. S. et al. Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros. Nat. Biotechnol. 34, 168–1179 (2016).

    Google Scholar 

  62. Taoudi, S. et al. Extensive hematopoietic stem cell generation in the AGM region via maturation of VE-cadherin+CD45+ pre-definitive HSCs. Cell Stem Cell 3, 99–108 (2008).

    Article  CAS  Google Scholar 

  63. Sugimura, R. et al. Haematopoietic stem and progenitor cells from human pluripotent stem cells. Nature 545, 432–438 (2017).

    Article  CAS  Google Scholar 

  64. Nimmerjahn, A., Kirchhoff, F. & Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314–1318 (2005).

    Article  CAS  Google Scholar 

  65. Frost, J. L. & Schafer, D. P. Microglia: architects of the developing nervous system. Trends Cell Biol. 26, 587–597 (2016).

    Article  Google Scholar 

  66. Li, Q. & Barres, B. A. Microglia and macrophages in brain homeostasis and disease. Nat. Rev. Immunol. 18, 225–242 (2018).

    Article  CAS  Google Scholar 

  67. Wang, Y. et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat. Immunol. 13, 753–760 (2012).

    Article  CAS  Google Scholar 

  68. Schilling, T., Nitsch, R., Heinemann, U., Hass, D. & Eder, C. Astrocyte-released cytokines induce ramification and outward K+ channel expression in microglia via distinct signalling pathways. Eur. J. Neurosci. 14, 463–473 (2001).

    Article  CAS  Google Scholar 

  69. Butovsky, O. et al. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci. 17, 131–143 (2014).

    Article  CAS  Google Scholar 

  70. Bohlen, C. J. et al. Diverse requirements for microglial survival, specification, and function revealed by defined-medium cultures. Neuron 94, 759–773 (2017).

    Article  CAS  Google Scholar 

  71. ElAli, A. & Rivest, S. Microglia ontology and signaling. Front. Cell Dev. Biol. 4, 72 (2016).

    Article  Google Scholar 

  72. Haenseler, W. et al. A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response. Stem Cell Rep. 8, 1727–1742 (2017).

    Article  CAS  Google Scholar 

  73. Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290 (2017).

    Article  CAS  Google Scholar 

  74. Lancaster, M. A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013).

    Article  CAS  Google Scholar 

  75. Muguruma, K., Nishiyama, A., Kawakami, H., Hashimoto, K. & Sasai, Y. Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Rep. 10, 537–550 (2015).

    Article  CAS  Google Scholar 

  76. Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016).

    Article  CAS  Google Scholar 

  77. Jo, J. et al. Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons. Cell Stem Cell 19, 248–257 (2016).

    Article  CAS  Google Scholar 

  78. Lindborg, B. A. et al. Rapid induction of cerebral organoids from human induced pluripotent stem cells using a chemically defined hydrogel and defined cell culture medium. Stem Cells Transl Med. 5, 970–979 (2016).

    Article  CAS  Google Scholar 

  79. Happle, C. et al. Pulmonary transplantation of human iPSC-derived macrophages ameliorates pulmonary alveolar proteinosis. Am. J. Respir. Crit. Care Med. https://doi.org/10.1164/rccm.201708-1562OC (2018).

    Article  PubMed  Google Scholar 

  80. Haideri, S. S. et al. Injection of embryonic stem cell derived macrophages ameliorates fibrosis in a murine model of liver injury. NPJ Regen. Med. 2, 14 (2017).

    Article  Google Scholar 

  81. van de Laar, L. et al. Yolk sac macrophages, fetal liver, and adult monocytes can colonize an empty niche and develop into functional tissue-resident macrophages. Immunity 44, 755–768 (2016).

    Article  Google Scholar 

  82. Spence, J. R. et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470, 105–109 (2011).

    Article  Google Scholar 

  83. Takebe, T. et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499, 481–484 (2013).

    Article  CAS  Google Scholar 

  84. Takasato, M. et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526, 64–568 (2015).

    Article  Google Scholar 

  85. Machnik, A. et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat. Med. 15, 545–552 (2009).

    Article  CAS  Google Scholar 

  86. Takeda, N. et al. Differential activation and antagonistic function of HIF-α isoforms in macrophages are essential for NO homeostasis. Genes Dev. 24, 491–501 (2010).

    Article  CAS  Google Scholar 

  87. Mirza, R., DiPietro, L. A. & Koh, T. J. Selective and specific macrophage ablation is detrimental to wound healing in mice. Am. J. Pathol. 175, 2454–2462 (2009).

    Article  CAS  Google Scholar 

  88. Eom, D. S. & Parichy, D. M. A macrophage relay for long-distance signaling during postembryonic tissue remodeling. Science 355, 1317–1320 (2017).

    Article  CAS  Google Scholar 

  89. Marin-Teva, J. L. et al. Microglia promote the death of developing Purkinje cells. Neuron 41, 535–547 (2004).

    Article  CAS  Google Scholar 

  90. Geutskens, S. B., Otonkoski, T., Pulkkinen, M. A., Drexhage, H. A. & Leenen, P. J. Macrophages in the murine pancreas and their involvement in fetal endocrine development in vitro. J. Leukoc. Biol. 78, 845–852 (2005).

    Article  CAS  Google Scholar 

  91. Banaei-Bouchareb, L., Peuchmaur, M., Czemichow, P. & Polak, M. A transient microenvironment loaded mainly with macrophages in the early developing human pancreas. J. Endocrinol. 188, 467–480 (2006).

    Article  CAS  Google Scholar 

  92. Brownjohn, P. W. et al. Functional studies of missense TREM2 mutations in human stem cell-derived microglia. Stem Cell Rep. 10, 1294–1307 (2018).

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  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

Authors
  1. Christopher Z. W. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tatsuya Kozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Florent Ginhoux
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding author

Correspondence to Florent Ginhoux.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Aorta-gonad-mesonephros

(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.

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41577-018-0054-y

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing