The use and limitations of single‐cell mass cytometry for studying human microglia function

Fernández-Zapata, Camila; Leman, Julia Kh; Priller, Josef; Böttcher, Chotima

doi:10.1111/bpa.12909

Cited by 23 publications

(16 citation statements)

References 87 publications

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“…Taking advantage of antibody coupling to non-radioactive isotopes of heavy metals that can be detected by mass spectrometry, cytometry by time of flight (CyTOF) enhances the study and analysis of very specific types of cells. 280 This technique allows the detection of a large number of cell types and the assessment of the immune cell activation state (around 60 markers) and overcomes the limitations of the use of fluorophores in flow cytometry. Using this technique, Couloume et al .…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications

Galoppin

Kari

Soldati

et al. 2022

Brain Communications

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Vitamin D deficiency has been associated with the risk of multiple sclerosis, disease activity and progression. Results from in vitro experiments, animal models and analysis of human samples from randomized controlled trials provide comprehensive data illustrating the pleiotropic actions of Vitamin D on the immune system. They globally result in immunomodulation by decreasing differentiation of effector T and B cells while promoting regulatory subsets. Vitamin D also modulates innate immune cells such as macrophages, monocytes and dendritic cells, and acts at the level of the blood-brain-barrier reducing immune cell trafficking. Vitamin D exerts additional activity within the central nervous system reducing microglial and astrocytic activation. The immunomodulatory role of Vitamin D detected in animal models of multiple sclerosis has suggested its potential therapeutic use for treating multiple sclerosis. In this review, we focus on recent published data describing the biological effects of Vitamin D in animal models of multiple sclerosis on immune cells, blood-brain-barrier function, activation of glial cells and its potential neuroprotective effects. Based on the current knowledge, we also discuss optimization of therapeutic interventions with Vitamin D in patients with multiple sclerosis, as well as new technologies allowing in-depth analysis of immune cell regulations by vitamin D.

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Section: Discussion and Perspectivesmentioning

confidence: 99%

Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications

Galoppin

Kari

Soldati

et al. 2022

Brain Communications

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show abstract

“…While we admit the importance of the transcriptome, such studies do not provide any information on functional protein expression. Upcoming multiplexed proteome studies, such as imaging masscytometry, should overcome the points (Fernández-Zapata et al, 2020 ). As abovementioned, there is no complex and specific immune memory in innate immunity, but the feature of heterogeneity might be a form of the memory in innate immunity.…”

Section: Microglia Heterogeneity and Roles For Modulating Activity Of...mentioning

confidence: 99%

Immune-Triggered Forms of Plasticity Across Brain Regions

Hikosaka

Kawano

Wada

et al. 2022

Front. Cell. Neurosci.

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Immune cells play numerous roles in the host defense against the invasion of microorganisms and pathogens, which induces the release of inflammatory mediators (e.g., cytokines and chemokines). In the CNS, microglia is the major resident immune cell. Recent efforts have revealed the diversity of the cell types and the heterogeneity of their functions. The refinement of the synapse structure was a hallmark feature of the microglia, while they are also involved in the myelination and capillary dynamics. Another promising feature is the modulation of the synaptic transmission as synaptic plasticity and the intrinsic excitability of neurons as non-synaptic plasticity. Those modulations of physiological properties of neurons are considered induced by both transient and chronic exposures to inflammatory mediators, which cause behavioral disorders seen in mental illness. It is plausible for astrocytes and pericytes other than microglia and macrophage to induce the immune-triggered plasticity of neurons. However, current understanding has yet achieved to unveil what inflammatory mediators from what immune cells or glia induce a form of plasticity modulating pre-, post-synaptic functions and intrinsic excitability of neurons. It is still unclear what ion channels and intracellular signaling of what types of neurons in which brain regions of the CNS are involved. In this review, we introduce the ubiquitous modulation of the synaptic efficacy and the intrinsic excitability across the brain by immune cells and related inflammatory cytokines with the mechanism for induction. Specifically, we compare neuro-modulation mechanisms by microglia of the intrinsic excitability of cerebellar Purkinje neurons with cerebral pyramidal neurons, stressing the inverted directionality of the plasticity. We also discuss the suppression and augmentation of the extent of plasticity by inflammatory mediators, as the meta-plasticity by immunity. Lastly, we sum up forms of immune-triggered plasticity in the different brain regions with disease relevance. Together, brain immunity influences our cognition, sense, memory, and behavior via immune-triggered plasticity.

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“…These 6 categories are (1) global structure preservation, (2) local structure preservation, (3) cluster reconstruction (assessing whether similar clusters can be reconstructed each time in the DR space), (4) cluster concordance (concordance of the clusters reconstructed in the DR space and the original space), (5) scRNA concordance (concordance with scRNA-seq data generated from the same samples when available), and (6) cell type-clustering concordance (concordance of the clusters reconstructed in the DR space and the cell typing results). In our study, the DR methods were assessed and ranked mainly by these metrics focusing on the accuracy of DR.…”

Section: Resultsmentioning

confidence: 99%

Comparative Analysis of Dimension Reduction Methods for Cytometry by Time-of-Flight Data

Wang

Yang

et al. 2022

Preprint

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Recently developed single-cell profiling technologies, such as single cell sequencing (scRNA-seq) and mass cytometry (CyTOF), provide critical biological insights from a large number of cells and a large number of features. While experimental and informatic techniques around scRNA-seq are much more advanced, research around CyTOF data analysis has severely lagged behind. However, CyTOF profiles the proteomics makeup of the single cells and are more closely related to disease phenotypes than scRNA-seq. CyTOF data are also dramatically different from scRNA-seq data in many aspects. This calls for the evaluation and development of statistical methods for CyTOF data. Dimension reduction (DR) is one of the most critical first steps of analyses of scRNA-seq and CyTOF data. Here, we benchmark 20 of these methods on 110 real and 425 synthetic CyTOF datasets, including 10 Imaging CyTOF datasets, for accuracy, scalability and usability. In particular, we checked the concordance of DR for CyTOF data against scRNA-seq data that were generated from the same samples. We found that SAUCIE and scvis surprisingly perform well across all categories, whereas UMAP particularly excels in downstream analyses and MDS preserves local and global structure well. Our results highlight the complementarity of existing tools, and that the choice of method should depend on the underlying data structure of the single cells. Based on these results, we develop a set of guidelines to help users select the best DR method for their dataset. Our freely available data and evaluation pipeline will aid in the development of improved DR algorithms specifically tailored to analyze data generated from the increasingly popular CyTOF technique.

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The use and limitations of single‐cell mass cytometry for studying human microglia function

Cited by 23 publications

References 87 publications

Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications

Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications

Immune-Triggered Forms of Plasticity Across Brain Regions

Comparative Analysis of Dimension Reduction Methods for Cytometry by Time-of-Flight Data

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