Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain

Chia, Kelda; Mazzolini, Julie; Mione, Marina; Sieger, Dirk

doi:10.7554/elife.31918

Cited by 66 publications

(92 citation statements)

References 87 publications

(115 reference statements)

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“…We chose 3 dpf, when macrophages start colonizing the brain and differentiate into early microglia (Figure 1a Figure S1; Mazzolini et al, 2018). As shown in Figure 1 and in recent publications, the 4C4 antibody is highly specific for zebrafish microglia and does not detect other cell types in the brain (Chia, Mazzolini, Mione, & Sieger, 2018;Ohnmacht et al, 2016;Tsarouchas et al, 2018). To confirm the purity of the sorted 4C4+ cell population, we isolated cells from two different transgenic backgrounds with either labeled neurons (NBT:dsRED) or labeled radial glial cell progenitors (zic4:mCherry; Distel et al, 2009;Peri & Nüsslein-Volhard, 2008).…”

Section: Larval Zebrafish Microglia Show a Rapid Differentiationmentioning

confidence: 99%

Gene expression profiling reveals a conserved microglia signature in larval zebrafish

Mazzolini

Clerc

Morisse

et al. 2019

Glia

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Microglia are the resident macrophages of the brain. Over the past decade, our understanding of the function of these cells has significantly improved. Microglia do not only play important roles in the healthy brain but are involved in almost every brain pathology. Gene expression profiling allowed to distinguish microglia from other macrophages and revealed that the full microglia signature can only be observed in vivo. Thus, animal models are irreplaceable to understand the function of these cells. One of the popular models to study microglia is the zebrafish larva. Due to their optical transparency and genetic accessibility, zebrafish larvae have been employed to understand a variety of microglia functions in the living brain. Here, we performed RNA sequencing of larval zebrafish microglia at different developmental time points: 3, 5, and 7 days post fertilization (dpf). Our analysis reveals that larval zebrafish microglia rapidly acquire the core microglia signature and many typical microglia genes are expressed from 3 dpf onwards. The majority of changes in gene expression happened between 3 and 5 dpf, suggesting that differentiation mainly takes place during these days. Furthermore, we compared the larval microglia transcriptome to published data sets of adult zebrafish microglia, mouse microglia, and human microglia. Larval microglia shared a significant number of expressed genes with their adult counterparts in zebrafish as well as with mouse and human microglia. In conclusion, our results show that larval zebrafish microglia mature rapidly and express the core microglia gene signature that seems to be conserved across species.

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Section: Larval Zebrafish Microglia Show a Rapid Differentiationmentioning

confidence: 99%

Gene expression profiling reveals a conserved microglia signature in larval zebrafish

Mazzolini

Clerc

Morisse

et al. 2019

Glia

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“…Mpeg1.1 : GFP and mpeg1.1 : mCherry reporter fish have been instrumental in characterizing the behavior of macrophages through live imaging in transgenic embryos, and the mpeg1.1 : Gal4 line for analyzing macrophage‐targeted gene function. Altogether, these studies have tremendously contributed to increasing our knowledge on the roles of macrophages in multiple processes of developmental physiology, as well as in pathologic mechanisms involved in human disease, such as inflammation, infection, and cancer . Whereas most of the field has initially focused on early macrophages taking advantage of the optical transparency of the zebrafish embryo and larvae, a growing number of investigators are now using these lines to address multiple aspects of macrophage biology in adults.…”

Section: Introductionmentioning

confidence: 99%

“…Altogether, these studies have tremendously contributed to increasing our knowledge on the roles of macrophages in multiple processes of developmental physiology, [14][15][16] as well as in pathologic mechanisms involved in human disease, such as inflammation, infection, 17,18 and cancer. [19][20][21] Whereas most of the field has initially focused on early macrophages taking advantage of the optical transparency of the zebrafish embryo and larvae, a growing number of investigators are now using these lines to address multiple aspects of macrophage biology in adults. This raises important questions, as the specificity of the mpeg1.1 driver in the adult hematopoietic system still remains to be determined.…”

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confidence: 99%

Themacrophage-expressed gene(mpeg)1identifies a subpopulation of B cells in the adult zebrafish

Ferrero

Gomez

lyer

et al. 2020

Journal of Leukocyte Biology

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The mononuclear phagocytic system consists of many cells, in particular macrophages, scattered throughout the body. However, there is increasing evidence for the heterogeneity of tissue‐resident macrophages, leading to a pressing need for new tools to discriminate mononuclear phagocytic system subsets from other hematopoietic lineages. Macrophage‐expressed gene (Mpeg)1.1 is an evolutionary conserved gene encoding perforin‐2, a pore‐forming protein associated with host defense against pathogens. Zebrafish mpeg1.1:GFP and mpeg1.1:mCherry reporters were originally established to specifically label macrophages. Since then more than 100 peer‐reviewed publications have made use of mpeg1.1‐driven transgenics for in vivo studies, providing new insights into key aspects of macrophage ontogeny, activation, and function. Whereas the macrophage‐specific expression pattern of the mpeg1.1 promoter has been firmly established in the zebrafish embryo, it is currently not known whether this specificity is maintained through adulthood. Here we report direct evidence that beside macrophages, a subpopulation of B‐lymphocytes is marked by mpeg1.1 reporters in most adult zebrafish organs. These mpeg1.1+ lymphoid cells endogenously express mpeg1.1 and can be separated from mpeg1.1+ macrophages by virtue of their light‐scatter characteristics using FACS. Remarkably, our analyses also revealed that B‐lymphocytes, rather than mononuclear phagocytes, constitute the main mpeg1.1‐positive population in irf8null myeloid‐defective mutants, which were previously reported to recover tissue‐resident macrophages in adulthood. One notable exception is skin macrophages, whose development and maintenance appear to be independent from irf8, similar to mammals. Collectively, our findings demonstrate that irf8 functions in myelopoiesis are evolutionary conserved and highlight the need for alternative macrophage‐specific markers to study the mononuclear phagocytic system in adult zebrafish.

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“…Mpeg1.1:GFP and mpeg1.1:mCherry reporter fish have been instrumental in characterizing the behavior of macrophages through live imaging in transgenic embryos, and the mpeg1.1:Gal4 line for analyzing macrophage-targeted gene function. Altogether, these studies have tremendously contributed to increasing our knowledge on the roles of macrophages in multiple processes of developmental physiology [14][15][16] , as well as in pathological mechanisms involved in human disease, such as inflammation, infection 17,18 and cancer [19][20][21] . However, while most of the field has initially focused on early macrophages taking advantage of the optical transparency of the zebrafish embryo and larvae, a growing number of investigators are now using these lines to address multiple aspects of macrophage biology in adults.…”

Section: Introductionmentioning

confidence: 99%

Themacrophage-expressed gene(mpeg)1identifies a subpopulation of B cells in the adult zebrafish

Ferrero

Gomez

Iyer

et al. 2019

Preprint

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SENTENCEMpeg1 is not a restricted macrophage marker, but also labels B cells in the adult zebrafish. Therefore, previously identified irf8-independent macrophages likely consist of B lymphocytes. 2 ABSTRACTThe mononuclear phagocytic system (MPS) consists of many cells, in particular macrophages, scattered throughout the body. However, there is increasing evidence for the heterogeneity of tissue-resident macrophages, leading to a pressing need for new tools to discriminate MPS subsets from other hematopoietic lineages. Mpeg1.1 is an evolutionary conserved gene encoding perforin-2, a pore-forming protein associated with host defense against pathogens. Zebrafish mpeg1.1:GFP and mpeg1.1:mCherry reporters were originally established to specifically label macrophages. Since, more than 100 peer-reviewed publications have made use of mpeg1.1-driven transgenics for in vivo studies, providing new insights into key aspects of macrophage ontogeny, activation and function. However, while the macrophagespecific expression pattern of the mpeg1.1 promoter has been firmly established in the zebrafish embryo, it is currently not known whether this specificity is maintained through adulthood. Here we report direct evidence that beside macrophages, a subpopulation of B-lymphocytes is marked by mpeg1.1 reporters in most adult zebrafish organs. These mpeg1.1 + lymphoid cells endogenously express mpeg1.1 and can be separated from mpeg1.1 + macrophages by virtue of their light-scatter characteristics using FACS. Remarkably, our analyses also revealed that Blymphocytes, rather than mononuclear phagocytes, constitute the main mpeg1.1positive population in irf8 null myeloid-defective mutants, which were previously reported to recover tissue-resident macrophages in adulthood. One notable exception are skin macrophages, whose development and maintenance appear to be independent from irf8, similar to mammals. Collectively, our findings demonstrate that irf8 functions in myelopoiesis are evolutionary conserved and highlight the need for alternative macrophage-specific markers to study the MPS in adult zebrafish.

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Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain

Cited by 66 publications

References 87 publications

Gene expression profiling reveals a conserved microglia signature in larval zebrafish

Gene expression profiling reveals a conserved microglia signature in larval zebrafish

Themacrophage-expressed gene(mpeg)1identifies a subpopulation of B cells in the adult zebrafish

Themacrophage-expressed gene(mpeg)1identifies a subpopulation of B cells in the adult zebrafish

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