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Made to order: emergency myelopoiesis and demand-adapted innate immune cell production

Abstract

Definitive haematopoiesis is the process by which haematopoietic stem cells, located in the bone marrow, generate all haematopoietic cell lineages in healthy adults. Although highly regulated to maintain a stable output of blood cells in health, the haematopoietic system is capable of extensive remodelling in response to external challenges, prioritizing the production of certain cell types at the expense of others. In this Review, we consider how acute insults, such as infections and cytotoxic drug-induced myeloablation, cause molecular, cellular and metabolic changes in haematopoietic stem and progenitor cells at multiple levels of the haematopoietic hierarchy to drive accelerated production of the mature myeloid cells needed to resolve the initiating insult. Moreover, we discuss how dysregulation or subversion of these emergency myelopoiesis mechanisms contributes to the progression of chronic inflammatory diseases and cancer.

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Fig. 1: Haematopoiesis is a process of continuous differentiation.
Fig. 2: Stress haematopoiesis uses bypass mechanisms and independent trajectories for lineage amplification.
Fig. 3: Emergency myelopoiesis mechanisms remodel the haematopoietic system to meet demand.
Fig. 4: Emergency myelopoiesis mechanisms are regulated by the bone marrow niche.
Fig. 5: Emergency myelopoiesis responses are specific to different infectious pathogens.
Fig. 6: Chronic inflammatory diseases dysregulate emergency myelopoiesis responses to accelerate disease.
Fig. 7: Solid cancers subvert emergency myelopoiesis mechanisms to promote tumour growth and metastasis.

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References

  1. Orkin, S. H. & Zon, L. I. Hematopoiesis: an evolving paradigm for stem cell biology. Cell 132, 631–644 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wilson, A. et al. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 135, 1118–1129 (2008).

    Article  CAS  PubMed  Google Scholar 

  3. Schoedel, K. B. et al. The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis. Blood 128, 2285–2296 (2016).

    Article  CAS  PubMed  Google Scholar 

  4. Rodriguez-Fraticelli, A. E. et al. Clonal analysis of lineage fate in native haematopoiesis. Nature 553, 212–216 (2018).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sun, J. et al. Clonal dynamics of native haematopoiesis. Nature 514, 322–327 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pietras, E. M. et al. Functionally distinct subsets of lineage-biased multipotent progenitors control blood production in normal and regenerative conditions. Cell Stem Cell 17, 35–46 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cabezas-Wallscheid, N. et al. Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA methylome analysis. Cell Stem Cell 15, 507–522 (2014).

    Article  CAS  PubMed  Google Scholar 

  8. Kang, Y. A., Pietras, E. M. & Passegue, E. Deregulated notch and Wnt signaling activates early-stage myeloid regeneration pathways in leukemia. J. Exp. Med. 217, e20190787 (2020).

    Article  Google Scholar 

  9. Sommerkamp, P. et al. Mouse multipotent progenitor 5 cells are located at the interphase between hematopoietic stem and progenitor cells. Blood 137, 3218–3224 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Akashi, K., Traver, D., Miyamoto, T. & Weissman, I. L. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404, 193–197 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Kondo, M., Weissman, I. L. & Akashi, K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91, 661–672 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Till, J. E. & McCulloch, E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res. 14, 213–222 (1961).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Spangrude, G. J., Heimfeld, S. & Weissman, I. L. Purification and characterization of mouse hematopoietic stem cells. Science 241, 58–62 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Muller-Sieburg, C. E., Whitlock, C. A. & Weissman, I. L. Isolation of two early B lymphocyte progenitors from mouse marrow: a committed pre-pre-B cell and a clonogenic Thy-1-lo hematopoietic stem cell. Cell 44, 653–662 (1986).

    Article  CAS  PubMed  Google Scholar 

  15. Oguro, H., Ding, L. & Morrison, S. J. SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors. Cell Stem Cell 13, 102–116 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Muller-Sieburg, C. E., Cho, R. H., Karlsson, L., Huang, J. F. & Sieburg, H. B. Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness. Blood 103, 4111–4118 (2004).

    Article  CAS  PubMed  Google Scholar 

  17. Muller-Sieburg, C. E., Cho, R. H., Thoman, M., Adkins, B. & Sieburg, H. B. Deterministic regulation of hematopoietic stem cell self-renewal and differentiation. Blood 100, 1302–1309 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Dykstra, B. et al. Long-term propagation of distinct hematopoietic differentiation programs in vivo. Cell Stem Cell 1, 218–229 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Morita, Y., Ema, H. & Nakauchi, H. Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J. Exp. Med. 207, 1173–1182 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yamamoto, R. et al. Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell 154, 1112–1126 (2013).

    Article  CAS  PubMed  Google Scholar 

  21. Osawa, M., Hanada, K., Hamada, H. & Nakauchi, H. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 273, 242–245 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Dong, F. et al. Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis. Nat. Cell Biol. 22, 630–639 (2020).

    Article  CAS  PubMed  Google Scholar 

  23. Pei, W. et al. Polylox barcoding reveals haematopoietic stem cell fates realized in vivo. Nature 548, 456–460 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  24. Naik, S. H. et al. Diverse and heritable lineage imprinting of early haematopoietic progenitors. Nature 496, 229–232 (2013).

    Article  ADS  CAS  PubMed  Google Scholar 

  25. Velten, L. et al. Human haematopoietic stem cell lineage commitment is a continuous process. Nat. Cell Biol. 19, 271–281 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tusi, B. K. et al. Population snapshots predict early haematopoietic and erythroid hierarchies. Nature 555, 54–60 (2018).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  27. Carrelha, J. et al. Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells. Nature 554, 106–111 (2018). This study uses single-cell transplantation techniques to reveal distinct patterns of lineage bias among HSCs, which are stable upon serial transplantation.

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Bowling, S. et al. An engineered CRISPR-Cas9 mouse line for simultaneous readout of lineage histories and gene expression profiles in single cells. Cell 181, 1693–1694 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Rodriguez-Fraticelli, A. E. et al. Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis. Nature 583, 585–589 (2020).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  30. Laurenti, E. & Gottgens, B. From haematopoietic stem cells to complex differentiation landscapes. Nature 553, 418–426 (2018).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  31. Paul, F. et al. Transcriptional heterogeneity and lineage commitment in myeloid progenitors. Cell 163, 1663–1677 (2015).

    Article  CAS  PubMed  Google Scholar 

  32. Kang, Y. A. et al. Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production. J. Exp. Med. 220, e20230088 (2023). This study identifies FcγR+ MPP3 cells as a self-reinforcing bypass mechanism for GMP amplification in inflammation and cancer.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Haas, S. et al. Inflammation-induced emergency megakaryopoiesis driven by hematopoietic stem cell-like megakaryocyte progenitors. Cell Stem Cell 17, 422–434 (2015). This study identifies a bypass mechanism by which HSCs can contribute directly to the megakaryocyte lineage under inflammatory conditions.

    Article  CAS  PubMed  Google Scholar 

  34. Morcos, M. N. F. et al. Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis. Nat. Commun. 13, 4504 (2022).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  35. Grinenko, T. et al. Hematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice. Nat. Commun. 9, 1898 (2018).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  36. Yanez, A. et al. Granulocyte-monocyte progenitors and monocyte-dendritic cell progenitors independently produce functionally distinct monocytes. Immunity 47, 890–902.e4 (2017). 

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Weinreb, C., Rodriguez-Fraticelli, A., Camargo, F. D. & Klein, A. M. Lineage tracing on transcriptional landscapes links state to fate during differentiation. Science 367, eaaw3381 (2020). Together with Yanez et al. (2017), this study identifies two distinct pathways for monocyte differentiation that have distinct functional characteristics.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Busch, K. et al. Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Nature 518, 542–546 (2015). This is the first major study to reveal, using fluorescent lineage-tracing approaches, that HSCs appear to make little contribution to steady-state haematopoiesis, with most daily blood production emanating from MPPs.

    Article  ADS  CAS  PubMed  Google Scholar 

  39. Sheikh, B. N. et al. MOZ (KAT6A) is essential for the maintenance of classically defined adult hematopoietic stem cells. Blood 128, 2307–2318 (2016).

    Article  CAS  PubMed  Google Scholar 

  40. Challen, G. A., Pietras, E. M., Wallscheid, N. C. & Singer, R. A. J. Simplified murine multipotent progenitor isolation scheme: establishing a consensus approach for multipotent progenitor identification. Exp. Hematol. 104, 55–63 (2021).

    Article  PubMed  Google Scholar 

  41. Hofer, T. & Rodewald, H. R. Differentiation-based model of hematopoietic stem cell functions and lineage pathways. Blood 132, 1106–1113 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Chapple, R. H. et al. Lineage tracing of murine adult hematopoietic stem cells reveals active contribution to steady-state hematopoiesis. Blood Adv. 2, 1220–1228 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sawen, P. et al. Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging. eLife 7, e41528 (2018).

    Article  Google Scholar 

  44. Sawai, C. M. et al. Hematopoietic stem cells are the major source of multilineage hematopoiesis in adult animals. Immunity 45, 597–609 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Scheiermann, C., Frenette, P. S. & Hidalgo, A. Regulation of leucocyte homeostasis in the circulation. Cardiovasc. Res. 107, 340–351 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Stark, M. A. et al. Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity 22, 285–294 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Heo, H. R. et al. Hormonal regulation of hematopoietic stem cells and their niche: a focus on estrogen. Int. J. Stem Cell 8, 18–23 (2015).

    Article  CAS  Google Scholar 

  48. Yan, H., Baldridge, M. T. & King, K. Y. Hematopoiesis and the bacterial microbiome. Blood 132, 559–564 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. King, K. Y. & Goodell, M. A. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nat. Rev. Immunol. 11, 685–692 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Takizawa, H. et al. Pathogen-induced TLR4-TRIF innate immune signaling in hematopoietic stem cells promotes proliferation but reduces competitive fitness. Cell Stem Cell 21, 225–240.e5 (2017).

    Article  CAS  PubMed  Google Scholar 

  51. Nagai, Y. et al. Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity 24, 801–812 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bakker, S. T. & Passegue, E. Resilient and resourceful: genome maintenance strategies in hematopoietic stem cells. Exp. Hematol. 41, 915–923 (2013).

    Article  CAS  PubMed  Google Scholar 

  53. Blanpain, C., Mohrin, M., Sotiropoulou, P. A. & Passegue, E. DNA-damage response in tissue-specific and cancer stem cells. Cell Stem Cell 8, 16–29 (2011).

    Article  CAS  PubMed  Google Scholar 

  54. Chandel, N. S., Jasper, H., Ho, T. T. & Passegue, E. Metabolic regulation of stem cell function in tissue homeostasis and organismal ageing. Nat. Cell Biol. 18, 823–832 (2016).

    Article  CAS  PubMed  Google Scholar 

  55. Beerman, I. & Rossi, D. J. Epigenetic control of stem cell potential during homeostasis, aging, and disease. Cell Stem Cell 16, 613–625 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ho, T. T. et al. Autophagy maintains the metabolism and function of young and old stem cells. Nature 543, 205–210 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  57. Paulson, R. F., Hariharan, S. & Little, J. A. Stress erythropoiesis: definitions and models for its study. Exp. Hematol. 89, 43–54.e2 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Noetzli, L. J., French, S. L. & Machlus, K. R. New insights into the differentiation of megakaryocytes from hematopoietic progenitors. Arterioscler. Thromb. Vasc. Biol. 39, 1288–1300 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Dancey, J. T., Deubelbeiss, K. A., Harker, L. A. & Finch, C. A. Neutrophil kinetics in man. J. Clin. Invest. 58, 705–715 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Boettcher, S. & Manz, M. G. Regulation of inflammation- and infection-driven hematopoiesis. Trends Immunol. 38, 345–357 (2017).

    Article  CAS  PubMed  Google Scholar 

  61. Mayadas, T. N., Cullere, X. & Lowell, C. A. The multifaceted functions of neutrophils. Annu. Rev. Pathol. 9, 181–218 (2014).

    Article  CAS  PubMed  Google Scholar 

  62. Manz, M. G. & Boettcher, S. Emergency granulopoiesis. Nat. Rev. Immunol. 14, 302–314 (2014).

    Article  CAS  PubMed  Google Scholar 

  63. Herault, A. et al. Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis. Nature 544, 53–58 (2017). This study describes how GMPs form clusters that serve as hubs of expansion and differentiation during EM.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  64. Olson, O. C., Kang, Y. A. & Passegue, E. Normal hematopoiesis is a balancing act of self-renewal and regeneration. Cold Spring Harb. Perspect. Med. 10, a035519 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Reynaud, D. et al. IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development. Cancer Cell 20, 661–673 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Essers, M. A. et al. IFNα activates dormant haematopoietic stem cells in vivo. Nature 458, 904–908 (2009). 

    Article  ADS  CAS  PubMed  Google Scholar 

  67. Baldridge, M. T., King, K. Y., Boles, N. C., Weksberg, D. C. & Goodell, M. A. Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection. Nature 465, 793–797 (2010). Together with Essers et al. (2009), this study demonstrates the role of inflammatory cytokines in activating HSCs in response to stress.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bernitz, J. M., Daniel, M. G., Fstkchyan, Y. S. & Moore, K. Granulocyte colony-stimulating factor mobilizes dormant hematopoietic stem cells without proliferation in mice. Blood 129, 1901–1912 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Pietras, E. M. et al. Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal. Nat. Cell Biol. 18, 607–618 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Etzrodt, M. et al. Inflammatory signals directly instruct PU.1 in HSCs via TNF. Blood 133, 816–819 (2019).

    Article  CAS  PubMed  Google Scholar 

  71. Yamashita, M. & Passegue, E. TNF-α coordinates hematopoietic stem cell survival and myeloid regeneration. Cell Stem Cell 25, 357–372.e7 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mossadegh-Keller, N. et al. M-CSF instructs myeloid lineage fate in single haematopoietic stem cells. Nature 497, 239–243 (2013).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  73. Challen, G. A., Boles, N. C., Chambers, S. M. & Goodell, M. A. Distinct hematopoietic stem cell subtypes are differentially regulated by TGFβ1. Cell Stem Cell 6, 265–278 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Bogeska, R. et al. Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging. Cell Stem Cell 29, 1273–1284 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Miyamoto, K. et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 1, 101–112 (2007).

    Article  CAS  PubMed  Google Scholar 

  76. Takubo, K. et al. Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. Cell Stem Cell 12, 49–61 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lin, K. K. et al. CD81 is essential for the re-entry of hematopoietic stem cells to quiescence following stress-induced proliferation via deactivation of the Akt pathway. PLoS Biol. 9, e1001148 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Pietras, E. M. et al. Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferons. J. Exp. Med. 211, 245–262 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Sato, T. et al. Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion. Nat. Med. 15, 696–700 (2009).

    Article  CAS  PubMed  Google Scholar 

  80. Chavez, J. S. et al. PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress. J. Exp. Med. 218, e20201169 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hernandez, G. et al. Pro-inflammatory cytokine blockade attenuates myeloid expansion in a murine model of rheumatoid arthritis. Haematologica 105, 585–597 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Beerman, I. et al. Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell 12, 413–425 (2013).

    Article  CAS  PubMed  Google Scholar 

  83. Munz, C. M. et al. Regeneration after blood loss and acute inflammation proceeds without contribution of primitive HSCs. Blood 141, 2483–2492 (2023). 

    CAS  PubMed  Google Scholar 

  84. Fanti, A. K. et al. Flt3- and Tie2-Cre tracing identifies regeneration in sepsis from multipotent progenitors but not hematopoietic stem cells. Cell Stem Cell 30, 207–218.e7 (2023). Together with Munz et al. (2023), this study demonstrates the importance of MPPs during diverse EM responses.

    Article  CAS  PubMed  Google Scholar 

  85. Baratono, S. R., Chu, N., Richman, L. P. & Behrens, E. M. Toll-like receptor 9 and interferon-γ receptor signaling suppress the B-cell fate of uncommitted progenitors in mice. Eur. J. Immunol. 45, 1313–1325 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Welner, R. S. et al. Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection. Blood 112, 3753–3761 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kato, H. et al. Infection perturbs Bach2- and Bach1-dependent erythroid lineage ‘choice’ to cause anemia. Nat. Immunol. 19, 1059–1070 (2018).

    Article  CAS  PubMed  Google Scholar 

  88. Swann, J. W. et al. IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors. J. Exp. Med. 217, e20200164 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Raundhal, M. et al. Blockade of IL-22 signaling reverses erythroid dysfunction in stress-induced anemias. Nat. Immunol. 22, 520–529 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Waight, J. D. et al. Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis. J. Clin. Invest. 123, 4464–4478 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Zhang, D. E. et al. Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein α-deficient mice. Proc. Natl Acad. Sci. USA 94, 569–574 (1997).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  92. Lieschke, G. J. et al. Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood 84, 1737–1746 (1994).

    Article  CAS  PubMed  Google Scholar 

  93. Liu, F., Wu, H. Y., Wesselschmidt, R., Kornaga, T. & Link, D. C. Impaired production and increased apoptosis of neutrophils in granulocyte colony-stimulating factor receptor-deficient mice. Immunity 5, 491–501 (1996).

    Article  CAS  PubMed  Google Scholar 

  94. Hirai, H. et al. C/EBPβ is required for ‘emergency’ granulopoiesis. Nat. Immunol. 7, 732–739 (2006). This study demonstrates that the generation of neutrophils in steady state and EM uses distinct transcription factors.

    Article  CAS  PubMed  Google Scholar 

  95. Zhang, H. et al. STAT3 controls myeloid progenitor growth during emergency granulopoiesis. Blood 116, 2462–2471 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lee, C. K. et al. STAT3 is a negative regulator of granulopoiesis but is not required for G-CSF-dependent differentiation. Immunity 17, 63–72 (2002).

    Article  CAS  PubMed  Google Scholar 

  97. Kurotaki, D. et al. IRF8 inhibits C/EBPα activity to restrain mononuclear phagocyte progenitors from differentiating into neutrophils. Nat. Commun. 5, 4978 (2014).

    Article  ADS  CAS  PubMed  Google Scholar 

  98. Meyer, M. A. et al. Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance. Nat. Commun. 9, 1250 (2018).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  99. de Bruin, A. M. et al. IFNγ induces monopoiesis and inhibits neutrophil development during inflammation. Blood 119, 1543–1554 (2012).

    Article  PubMed  Google Scholar 

  100. Pinho, S. & Frenette, P. S. Haematopoietic stem cell activity and interactions with the niche. Nat. Rev. Mol. Cell Biol. 20, 303–320 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Kunisaki, Y. et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature 502, 637–643 (2013).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  102. Bruns, I. et al. Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion. Nat. Med. 20, 1315–1320 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wu, Q. Z. et al. Resilient anatomy and local microplasticity of naïve and stress hematopoiesis. Preprint at bioRxiv https://doi.org/10.1101/2022.05.23.492315 (2022).

  104. Zhang, J. et al. In situ mapping identifies distinct vascular niches for myelopoiesis. Nature 590, 457–462 (2021). This study identifies the vascular niches for steady state and EM, describing granulocyte production lines organized along sinusoidal vessels.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  105. Cain, D. W., Snowden, P. B., Sempowski, G. D. & Kelsoe, G. Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism. PLoS ONE 6, e19957 (2011).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  106. Casanova-Acebes, M. et al. Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell 153, 1025–1035 (2013). This study identifies neutrophil clearance as a driver of circadian regulation of HSPCs in the bone marrow.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kanayama, M. et al. Skewing of the population balance of lymphoid and myeloid cells by secreted and intracellular osteopontin. Nat. Immunol. 18, 973–984 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Grassinger, J. et al. Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with α9β1 and α4β1 integrins. Blood 114, 49–59 (2009).

    Article  CAS  PubMed  Google Scholar 

  109. Nilsson, S. K. et al. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 106, 1232–1239 (2005).

    Article  CAS  PubMed  Google Scholar 

  110. Stier, S. et al. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J. Exp. Med. 201, 1781–1791 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Zhu, J. et al. Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells. Blood 109, 3706–3712 (2007).

    Article  CAS  PubMed  Google Scholar 

  112. Haltalli, M. L. R. et al. Manipulating niche composition limits damage to haematopoietic stem cells during Plasmodium infection. Nat. Cell Biol. 22, 1399–1410 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Basu, S., Zhang, H. H., Quilici, C. & Dunn, A. R. Candida albicans can stimulate stromal cells resulting in enhanced granulopoiesis. Stem Cell Dev. 13, 39–50 (2004).

    Article  CAS  Google Scholar 

  114. Boettcher, S. et al. Endothelial cells translate pathogen signals into G-CSF-driven emergency granulopoiesis. Blood 124, 1393–1403 (2014). 

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Boettcher, S. et al. Cutting edge: LPS-induced emergency myelopoiesis depends on TLR4-expressing nonhematopoietic cells. J. Immunol. 188, 5824–5828 (2012). Together with Boettcher et al. (2014), this study identifies the critical role of bone marrow endothelial cells in sensing LPS and secreting cytokines to activate EM in HSPCs.

    Article  CAS  PubMed  Google Scholar 

  116. Andonegui, G. et al. Endothelium-derived Toll-like receptor-4 is the key molecule in LPS-induced neutrophil sequestration into lungs. J. Clin. Invest. 111, 1011–1020 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Zhan, Y., Lieschke, G. J., Grail, D., Dunn, A. R. & Cheers, C. Essential roles for granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF in the sustained hematopoietic response of Listeria monocytogenes-infected mice. Blood 91, 863–869 (1998).

    Article  CAS  PubMed  Google Scholar 

  118. Basu, S. et al. “Emergency” granulopoiesis in G-CSF-deficient mice in response to Candida albicans infection. Blood 95, 3725–3733 (2000).

    Article  CAS  PubMed  Google Scholar 

  119. Heidt, T. et al. Chronic variable stress activates hematopoietic stem cells. Nat. Med. 20, 754–758 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Tang, Y. et al. Norepinephrine modulates myelopoiesis after experimental thermal injury with sepsis. Ann. Surg. 233, 266–275 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Maestroni, G. J., Togni, M. & Covacci, V. Norepinephrine protects mice from acute lethal doses of carboplatin. Exp. Hematol. 25, 491–494 (1997).

    CAS  PubMed  Google Scholar 

  122. Vasamsetti, S. B. et al. Sympathetic neuronal activation triggers myeloid progenitor proliferation and differentiation. Immunity 49, 93–106.e7 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Askenase, M. H. et al. Bone-marrow-resident NK cells prime monocytes for regulatory function during infection. Immunity 42, 1130–1142 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Rosen, H., Gordon, S. & North, R. J. Exacerbation of murine listeriosis by a monoclonal antibody specific for the type 3 complement receptor of myelomonocytic cells: absence of monocytes at infective foci allows Listeria to multiply in nonphagocytic cells. J. Exp. Med. 170, 27–37 (1989).

    Article  CAS  PubMed  Google Scholar 

  125. Serbina, N. V., Hohl, T. M., Cherny, M. & Pamer, E. G. Selective expansion of the monocytic lineage directed by bacterial infection. J. Immunol. 183, 1900–1910 (2009).

    Article  CAS  PubMed  Google Scholar 

  126. Beshara, R. et al. Alteration of Flt3-ligand-dependent de novo generation of conventional dendritic cells during influenza infection contributes to respiratory bacterial superinfection. PLoS Pathog. 14, e1007360 (2018). This study shows how adaptation of the haematopoietic system to one perturbation actually decreases its ability to respond to other stimuli, highlighting the importance of specificity in EM responses and the evolutionary cost of EM mechanisms.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Karsunky, H., Merad, M., Cozzio, A., Weissman, I. L. & Manz, M. G. Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo. J. Exp. Med. 198, 305–313 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Pedersen, S. F. & Ho, Y. C. SARS-CoV-2: a storm is raging. J. Clin. Invest. 130, 2202–2205 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Merad, M. & Martin, J. C. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat. Rev. Immunol. 20, 355–362 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Barnes, B. J. et al. Targeting potential drivers of COVID-19: neutrophil extracellular traps. J. Exp. Med. 217, e20200652 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Cao, X. COVID-19: immunopathology and its implications for therapy. Nat. Rev. Immunol. 20, 269–270 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Wilk, A. J. et al. Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19. J. Exp. Med. 218, e20210582 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Wang, X. et al. Dysregulated hematopoiesis in bone marrow marks severe COVID-19. Cell Discov. 7, 60 (2021). This study identifies activation of EM in HSPCs as a marker of severe COVID-19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Silvin, A. et al. Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19. Cell 182, 1401–1418.e18 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wilson, J. G. et al. Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis. JCI Insight 5, e140289 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Cabrera, L. E. et al. Characterization of low-density granulocytes in COVID-19. PLoS Pathog. 17, e1009721 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Schultze, J. L. & Aschenbrenner, A. C. COVID-19 and the human innate immune system. Cell 184, 1671–1692 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Quail, D. F. et al. Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF. Nat. Cell Biol. 19, 974–987 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Nagareddy, P. R. et al. Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity. Cell Metab. 19, 821–835 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Luo, Y. et al. Microbiota from obese mice regulate hematopoietic stem cell differentiation by altering the bone niche. Cell Metab. 22, 886–894 (2015).

    Article  CAS  PubMed  Google Scholar 

  141. Nagareddy, P. R. et al. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab. 17, 695–708 (2013). 

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Edgar, L. et al. Hyperglycemia induces trained immunity in macrophages and their precursors and promotes atherosclerosis. Circulation 144, 961–982 (2021). Together with Nagareddy et al. (2013), this study demonstrates how systemic metabolic disease can activate EM and induce central trained immunity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Regan-Komito, D. et al. GM-CSF drives dysregulated hematopoietic stem cell activity and pathogenic extramedullary myelopoiesis in experimental spondyloarthritis. Nat. Commun. 11, 155 (2020).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  144. Al-Mossawi, M. H. et al. Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis. Nat. Commun. 8, 1510 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  145. Cortez-Retamozo, V. et al. Origins of tumor-associated macrophages and neutrophils. Proc. Natl Acad. Sci. USA 109, 2491–2496 (2012).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  146. Franklin, R. A. et al. The cellular and molecular origin of tumor-associated macrophages. Science 344, 921–925 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  147. Leach, J., Morton, J. P. & Sansom, O. J. Neutrophils: homing in on the myeloid mechanisms of metastasis. Mol. Immunol. 110, 69–76 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Engblom, C. et al. Osteoblasts remotely supply lung tumors with cancer-promoting SiglecF(high) neutrophils. Science 358, eaal5081 (2017). 

    Article  PubMed  PubMed Central  Google Scholar 

  149. Hao, X. et al. Osteoprogenitor-GMP crosstalk underpins solid tumor-induced systemic immunosuppression and persists after tumor removal. Cell Stem Cell 30, 648–664.e8 (2023). Together with Engblom et al. (2017), this study identifies the role of activated bone marrow stromal cells in driving pathogenic EM activation during cancer.

    Article  CAS  PubMed  Google Scholar 

  150. Lin, E. Y., Nguyen, A. V., Russell, R. G. & Pollard, J. W. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J. Exp. Med. 193, 727–740 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Wculek, S. K. & Malanchi, I. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature 528, 413–417 (2015).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  152. Kowanetz, M. et al. Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes. Proc. Natl Acad. Sci. USA 107, 21248–21255 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  153. McAllister, S. S. et al. Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell 133, 994–1005 (2008). This study demonstrates the role of tumour-activated myelopoiesis in creating a tumour-promoting systemic environment.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Coffelt, S. B. et al. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature 522, 345–348 (2015).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  155. Consonni, F. M. et al. Heme catabolism by tumor-associated macrophages controls metastasis formation. Nat. Immunol. 22, 595–606 (2021).

    Article  CAS  PubMed  Google Scholar 

  156. Koelwyn, G. J. et al. Myocardial infarction accelerates breast cancer via innate immune reprogramming. Nat. Med. 26, 1452–1458 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  157. Hughes, R. et al. Perivascular M2 macrophages stimulate tumor relapse after chemotherapy. Cancer Res. 75, 3479–3491 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Shree, T. et al. Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev. 25, 2465–2479 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. DeNardo, D. G. et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 1, 54–67 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Marigo, I. et al. Tumor-induced tolerance and immune suppression depend on the C/EBPβ transcription factor. Immunity 32, 790–802 (2010).

    Article  CAS  PubMed  Google Scholar 

  161. Pylayeva-Gupta, Y., Lee, K. E., Hajdu, C. H., Miller, G. & Bar-Sagi, D. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell 21, 836–847 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Strauss, L. et al. RORC1 regulates tumor-promoting “emergency” granulo-monocytopoiesis. Cancer Cell 28, 253–269 (2015).

    Article  CAS  PubMed  Google Scholar 

  163. Strauss, L. et al. Targeted deletion of PD-1 in myeloid cells induces antitumor immunity. Sci. Immunol. 5, eaay1863 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Kaufmann, E. et al. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172, 176–190.e19 (2018).

    Article  CAS  PubMed  Google Scholar 

  165. Verovskaya, E. V., Dellorusso, P. V. & Passegue, E. Losing sense of self and surroundings: hematopoietic stem cell aging and leukemic transformation. Trends Mol. Med. 25, 494–515 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  166. Kwok, A. J. et al. Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis. Nat. Immunol. 24, 767–779 (2023).

    Article  CAS  PubMed  Google Scholar 

  167. Hirschhorn, D. et al. T cell immunotherapies engage neutrophils to eliminate tumor antigen escape variants. Cell 186, 1432–1447.e17 (2023).

    Article  CAS  PubMed  Google Scholar 

  168. Gungabeesoon, J. et al. A neutrophil response linked to tumor control in immunotherapy. Cell 186, 1448–1464.e20 (2023).

    Article  CAS  PubMed  Google Scholar 

  169. Mauer, A. M. Diurnal variation of proliferative activity in the human bone marrow. Blood 26, 1–7 (1965).

    Article  CAS  PubMed  Google Scholar 

  170. Ohdo, S. et al. Chronopharmacology of granulocyte colony-stimulating factor in mice. J. Pharmacol. Exp. Ther. 285, 242–246 (1998).

    CAS  PubMed  Google Scholar 

  171. Lucas, D., Battista, M., Shi, P. A., Isola, L. & Frenette, P. S. Mobilized hematopoietic stem cell yield depends on species-specific circadian timing. Cell Stem Cell 3, 364–366 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Mendez-Ferrer, S., Lucas, D., Battista, M. & Frenette, P. S. Haematopoietic stem cell release is regulated by circadian oscillations. Nature 452, 442–447 (2008).

    Article  ADS  CAS  PubMed  Google Scholar 

  173. Golan, K. et al. Daily onset of light and darkness differentially controls hematopoietic stem cell differentiation and maintenance. Cell Stem Cell 23, 572–585.e7 (2018).

    Article  CAS  PubMed  Google Scholar 

  174. Olsson, A. et al. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature 537, 698–702 (2016).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  175. Puram, R. V. et al. Core circadian clock genes regulate leukemia stem cells in AML. Cell 165, 303–316 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Netea, M. G. et al. Defining trained immunity and its role in health and disease. Nat. Rev. Immunol. 20, 375–388 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Mitroulis, I. et al. Modulation of myelopoiesis progenitors is an integral component of trained immunity. Cell 172, 147–161.e12 (2018). This study identifies the importance of alterations in myeloid progenitors in trained immunity of downstream myeloid cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. de Laval, B. et al. C/EBPβ-dependent epigenetic memory induces trained immunity in hematopoietic stem cells. Cell Stem Cell 26, 793 (2020).

    Article  PubMed  Google Scholar 

  179. Hormaechea-Agulla, D. et al. Chronic infection drives Dnmt3a-loss-of-function clonal hematopoiesis via IFNγ signaling. Cell Stem Cell 28, 1428–1442.e6 (2021). This study demonstrates the role of inflammatory cytokines in driving clonal expansion of HSCs with pre-leukaemic mutations.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Avagyan, S. et al. Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis. Science 374, 768–772 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  181. Caiado, F. et al. Aging drives Tet2+/− clonal hematopoiesis via IL-1 signaling. Blood 141, 886–903 (2023).

    Article  CAS  PubMed  Google Scholar 

  182. Meisel, M. et al. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature 557, 580–584 (2018).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  183. Fuster, J. J. et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 355, 842–847 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  184. Zhang, Q. et al. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 525, 389–393 (2015).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  185. Mitchell, C. A. et al. Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing. Nat. Cell Biol. 25, 30–41 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Yamashita, M., Dellorusso, P. V., Olson, O. C. & Passegue, E. Dysregulated haematopoietic stem cell behaviour in myeloid leukaemogenesis. Nat. Rev. Cancer 20, 365–382 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

J.W.S. discloses support for this work from William Raveis Charitable Fund Fellowship of the Damon Runyon Cancer Research Foundation DRG-2493-23 and EMBO fellowship ALTF-196-2021. O.C.O. acknowledges support from CRI/Margaret Damman Eisner postdoctoral fellowship CRI3617. E.P. acknowledges support from NIH R01CA184014 and NIH R35HL135763. The funders had no role in the preparation of this manuscript.

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Swann, J.W., Olson, O.C. & Passegué, E. Made to order: emergency myelopoiesis and demand-adapted innate immune cell production. Nat Rev Immunol (2024). https://doi.org/10.1038/s41577-024-00998-7

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