Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models

Ajami, Bahareh; Samusik, Nikolay; Wieghofer, Peter; Ho, Peggy P.; Crotti, Andrea; Bjornson, Zach B.; Prinz, Marco; Fantl, Wendy J.; Nolan, Garry P.; Steinman, Lawrence

doi:10.1038/s41593-018-0100-x

Cited by 263 publications

(258 citation statements)

References 61 publications

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“…Of note, this subset is even more abundant in the spinal cord at the peak of the diseases reaching up to 60% of total microglia (Wlodarczyk, unpublished). The emergence of the CD11c+ microglia is a dynamic process starting at the onset, reaching a maximum at the peak and contracting in the chronic phase of EAE (77,138). These cells are localized in the demyelinated spinal cord lesions (33).…”

Section: Multiple Sclerosismentioning

confidence: 99%

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

2020

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Microglial heterogeneity has been the topic of much discussion in the scientific community. Elucidation of their plasticity and adaptability to disease states triggered early efforts to characterize microglial subsets. Over time, their phenotypes, and later on their homeostatic signature, were revealed, through the use of increasingly advanced transcriptomic techniques. Recently, an increasing number of these "microglial signatures" have been reported in various homeostatic and disease contexts. Remarkably, many of these states show similar overlapping microglial gene expression patterns, both in homeostasis and in disease or injury. In this review, we integrate information from these studies, and we propose a unique subset, for which we introduce a core signature, based on our own research and reports from the literature. We describe that this subset is found in development and in normal aging as well as in diverse diseases. We discuss the functions of this subset as well as how it is induced.

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Section: Multiple Sclerosismentioning

confidence: 99%

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

2020

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“…These studies are a strong first step investigating potential sex differences in unique microglial subtypes such as disease‐associated microglia, and highlight the practical usage of new single‐cell techniques. Interestingly, a model of neuroinflammation revealed combinatorial cytokine secretion, specifically of TNF‐ɑ and GM‐CSF, whereas microglia isolated from models of neurodegeneration maintained monosecretion (Ajami et al, ). Unfortunately, these current rodent studies utilizing CyTOF have either used one sex or do not report on the sex of the animals used.…”

Section: Intrinsic Differences Between Brain Regions May Impart Sex‐smentioning

confidence: 99%

Microglia and sexual differentiation of the developing brain: A focus on ontogeny and intrinsic factors

Bordt

Ceasrine

Bilbo

2019

Glia

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Sexual differentiation of the brain during early development likely underlies the strong sex biases prevalent in many neurological conditions. Mounting evidence indicates that microglia, the innate immune cells of the central nervous system, are intricately involved in these sex‐specific processes of differentiation. In this review, we synthesize literature demonstrating sex differences in microglial number, morphology, transcriptional state, and functionality throughout spatiotemporal development as well as highlight current literature regarding ontogeny of microglia. Along with vanRyzin et al. in this issue, we explore the idea that differences in microglia imparted by chromosomal or ontogeny‐related programming can influence microglial‐driven sexual differentiation of the brain, as well as the idea that extrinsic differences in the male and female brain microenvironment may in turn impart sex differences in microglia.

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“…The dynamic changes of microglia activation and the contribution of recruited myeloid cells in the course of lesion development and resolution has recently been studied by single‐cell‐mass cytometry (CYTOF), which allows to determine the dynamic changes of different cell populations by a combined marker profile (Ajami et al, ). The study confirms earlier work discussed above by showing that already in the preclinical phase of the disease microglia become activated and circulating monocytes are recruited into the inflammatory lesions.…”

Section: Microglia and Macrophages In Inflammatory Diseases Of Rodentsmentioning

confidence: 99%

“… Note : The table compares the key features of inflammatory lesions in the central nervous system mediated by different T‐cell populations, B‐cells, and innate immunity in rodent models and humans, also describing the reaction patterns of microglia/macrophages and astrocytes. References 1: Ajami et al (), 2: Ben‐Nun, Wekerle, and Cohen (), Lassmann et al (), 4: Wolf et al (), 5: Blaabjerg et al (). 6: Mayo et al (), 7: Basso et al (). 8: Bradl and Lassmann (), 9: Linington, Bradl, Lassmann, Brunner, and Vass (), 10: Misu et al (), 11: Pohl et al, , 12: Storch et al (). 13: Bien et al (), 14: Cabarrocas, Bauer, Piaggio, Liblau, and Lassmann (), 15: Dauvilliers et al (), 16: Ji, Perchellet, and Goverman (), 17: Laukoter et al (), 18: Na et al (), 19: Saxena et al (), 20: Steinbach et al (), 21: Tröscher et al (). 22: Machado‐Santos et al (), 23: van Nierop et al (), 24: Zrzavy et al (). 25: Felts et al (), 26: Marik, Felts, Bauer, Lassmann, and Smith (), 27: Nau and Brück (2002). …”

Section: Introductionmentioning

confidence: 99%

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Pathology of inflammatory diseases of the nervous system: Human disease versus animal models

Lassmann

2019

Glia

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Numerous recent studies have been performed to elucidate the function of microglia, macrophages, and astrocytes in inflammatory diseases of the central nervous system. Regarding myeloid cells a core pattern of activation has been identified, starting with the activation of resident homeostatic microglia followed by recruitment of blood borne myeloid cells. An initial state of proinflammatory activation is at later stages followed by a shift toward an‐anti‐inflammatory and repair promoting phenotype. Although this core pattern is similar between experimental models and inflammatory conditions in the human brain, there are important differences. Even in the normal human brain a preactivated microglia phenotype is evident, and there are disease specific and lesion stage specific differences in the contribution between resident and recruited myeloid cells and their lesion state specific activation profiles. Reasons for these findings reside in species related differences and in differential exposure to different environmental cues. Most importantly, however, experimental rodent studies on brain inflammation are mainly focused on autoimmune encephalomyelitis, while there is a very broad spectrum of human inflammatory diseases of the central nervous system, triggered and propagated by a variety of different immune mechanisms.

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Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models

Cited by 263 publications

References 61 publications

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

Microglia and sexual differentiation of the developing brain: A focus on ontogeny and intrinsic factors

Pathology of inflammatory diseases of the nervous system: Human disease versus animal models

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