Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution

Masuda, Takahiro; Sankowski, Roman; Staszewski, Ori; Böttcher, Chotima; Amann, Lukas; Sagar,; Scheiwe, Christian; Nessler, Stefan; Kunz, Patrik; Loo, Geert; Coenen, Volker A.; Reinacher, Peter C.; Michel, Anna; Sure, Ulrich; Gold, Ralf; Grün, Dominic; Priller, Josef; Stadelmann, Christine; Prinz, Marco

doi:10.1038/s41586-019-0924-x

Cited by 981 publications

(1,066 citation statements)

References 35 publications

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“…Interestingly, the authors were not able to detect an effect of sex on microglial diversity during normal development. Masuda et al also report a reduced heterogeneity in mouse microglia with increasing developmental stage (Masuda et al, ). A total of 10 microglial clusters are identified with a reported strong regional specificity, mirroring that of previous reports (Grabert et al, ).…”

Section: Microgliamentioning

confidence: 94%

“…In comparison, through the analysis of 1,180 human microglia from resected human brain tissue, Masuda et al report four distinct clusters. Although no formal comparison was carried out, the authors report a certain degree of conservation in the homeostatic profile but also distinct gene expression patterns that “partially overlap with those of adult mouse microglia” (Masuda et al, ). Commenting on regional differences in human microglia remains difficult, as resected tissue is typically obtained as part of the surgical treatment for temporal lobe epilepsy.…”

Section: Microgliamentioning

confidence: 99%

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Species differences in immune‐mediated CNS tissue injury and repair: A (neuro)inflammatory topic

Healy

Yaqubi

Ludwin

et al. 2019

Glia

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Cells of the adaptive and innate immune systems in the brain parenchyma and in the meningeal spaces contribute to physiologic functions and disease states in the central nervous system (CNS). Animal studies have demonstrated the involvement of immune constituents, along with major histocompatibility complex (MHC) molecules, in neural development and rare genetic disorders (e.g., colony stimulating factor 1 receptor [CSF1R] deficiency). Genome wide association studies suggest a comparable role of the immune system in humans. Although the CNS can be the target of primary autoimmune disorders, no current experimental model captures all of the features of the most common human disorder placed in this category, multiple sclerosis (MS). Such features include spontaneous onset, environmental contributions, and a recurrent/progressive disease course in a genetically predisposed host. Numerous therapeutic interventions related to antigen and cytokine specific therapies have demonstrated effectiveness in experimental autoimmune encephalomyelitis (EAE), the animal model used to define principles underlying immune‐mediated mechanisms in MS. Despite the similarities in the two diseases, most treatments used to ameliorate EAE have failed to translate to the human disease. As directly demonstrated in animal models and implicated by correlative studies in humans, adaptive and innate immune constituents within the systemic compartment and resident in the CNS contribute to the disease course of neurodegenerative and neurobehavioral disorders. The expanding knowledge of the molecular properties of glial cells provides increasing insights into species related variables. These variables affect glial bidirectional interactions with the immune system as well as their own production of “immune molecules” that mediate tissue injury and repair.

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Section: Microgliamentioning

confidence: 94%

Section: Microgliamentioning

confidence: 99%

Species differences in immune‐mediated CNS tissue injury and repair: A (neuro)inflammatory topic

Healy

Yaqubi

Ludwin

et al. 2019

Glia

View full text Add to dashboard Cite

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“…In particular, subsets of the cells already express markers for phagocytic activation, for oxygen radical productions, such as for instance NADPH oxidase (CYBB) and for antigen presentation (MHC Class I and Class II antigens and costimulatory molecules) and these activation markers are even expressed in microglia, which still show otherwise a homeostatic marker profile with reactivity for TMEM119 and P2RY12 (Wimmer et al, ; Zrzavy et al, ). This is also reflected in gene expression, revealing additional and more complex clusters of microglia phenotypes (Masuda et al, ) and by different age related gene expression patterns between mice and humans (Galatro et al, ). Another difference between rodent and human microglia is the abundance of dystrophic or senescent microglia, containing iron or ferritin in humans (Lopes, Sparks, & Streit, ; Streit, Sammons, Kuhns, & Sparks, ), which appears to be related to age dependent iron accumulation in the normal human brain (Hallgren & Sourander, ; Hametner et al, ).…”

Section: Microglia In the Normal Rodent And Human Brainmentioning

confidence: 99%

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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“…Through development, microglia express an age‐dependent gene signature and morphology, shifting from an ameboid morphology (large round soma, few to no processes) in early life to a ramified morphology (smaller soma, many complex processes) as the animal matures . In the adult animal, microglial morphology differs throughout the brain depending upon the tissue type, region, age, sex and presence or absence of an immune challenge or injury . Very broadly, however, microglia display a highly ramified “surveillant” morphology under unstimulated conditions, at which time they are highly motile, with continuous extension and retraction of their thin long processes, whereas the soma remains relatively stationary.…”

Section: Microgliamentioning

confidence: 99%

“…During brain development, they are important in regulating neuronal survival and death, synaptogenesis, and angiogenesis and, in adults, they are key in responding to brain injury and pathogens . Recently, additional roles for these cells in the healthy brain are starting to emerge along with evidence that subtypes with distinct functions are important in central responses to challenge . The present review not only provides a brief overview of the known roles of microglia in development and in responding to pathogens and injury, but also discusses new evidence suggesting that microglia play an integral role in at least two fairly disparate physiological functions in the healthy adult animal: cognition and satiety signalling.…”

Section: Introductionmentioning

confidence: 99%

Microglial regulation of satiety and cognition

Luca

Miller

Sominsky

et al. 2020

J Neuroendocrinology

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Microglia have been known for decades as key immune cells that shape the central nervous system (CNS) during development and respond to brain pathogens and injury in adult life. Recent findings now suggest that these cells also play a highly complex role in several other functions of the CNS. In this review, we provide a brief overview of the established microglial functions in development and disease. We also discuss emerging research suggesting that microglia are important for both cognitive function and the regulation of food intake. With respect to cognitive function, current data suggest microglia are not indispensable for neurogenesis, synaptogenesis or cognition in the healthy young adult, although they crucially modulate and support these functions. In doing so, they are likely important in supporting the balance between apoptosis and survival of newborn neurones and in orchestrating appropriate synaptic remodelling in response to a learning stimulus. We also explore the possibility of a role for microglia in feeding and satiety. Microglia have been implicated in both appetite suppression with sickness and obesity and in promoting feeding under some conditions and we discuss these findings here, highlighting the contribution of these cells to healthy brain function.

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Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution

Cited by 981 publications

References 35 publications

Species differences in immune‐mediated CNS tissue injury and repair: A (neuro)inflammatory topic

Species differences in immune‐mediated CNS tissue injury and repair: A (neuro)inflammatory topic

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

Microglial regulation of satiety and cognition

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