Single-cell RNA-seq analysis reveals compartment-specific heterogeneity and plasticity of microglia

Zheng, Junying; Ru, Wenjuan; Adolacion, Jay R T.; Spurgat, Michael S.; Liu, Xin; Yuan, Subo; Liang, Rommel X.; Dong, Jianli; Potter, Andrew; Potter, S. Steven; Chen, Ken; Chen, Rui; Varadarajan, Navin; Tang, Shao-Jun

doi:10.1016/j.isci.2021.102186

Cited by 36 publications

(30 citation statements)

References 40 publications

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“…Despite the emerging evidence from animal models of the existence of distinct transcriptional profiles in glial cells [3, 10, 12, 13], little information is known about the heterogeneity within glial cells from human tissues. To the best of our knowledge, this is the first study to elucidate the cellular and molecular complexity of glial cells, including SGCs in the DRG and astrocytes, microglia, and oligodendrocytes in the spinal cord using 10× Genomics snRNA-seq.…”

Section: Discussionmentioning

confidence: 99%

“…van Weperen et al performed scRNA-seq on mouse stellate ganglia and divided SGCs into six distinct transcriptomic subtypes [3]. Zheng et al performed scRNA-seq to compare microglial subtypes in the cortex and spinal cord identifying three subclusters in the cortex and two in the spinal cord and showing distinct subpopulations between spinal and cortical microglia [13]. Using a combination of scRNA-seq and multicolor flow cytometry, Sousa et al identified distinct microglial activation profiles under inflammation, which are substantially different from neurodegenerative disease-related profiles [14].…”

Section: Introductionmentioning

confidence: 99%

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Single-nucleus transcriptomic analysis reveals divergence of glial cells in peripheral somatosensory system between human and mouse

Zhang

Wei

Liu

et al. 2022

Preprint

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Glial cells play a crucial role in regulating physiological and pathological functions, such as sensation, infections, acute injuries, and chronic neurodegenerative disorders. Glial cells include astrocytes, microglia, and oligodendrocytes in the central nervous system (CNS) and satellite glial cells (SGCs) in the peripheral nervous system (PNS). Despite the understanding of glial subtypes and functional heterogeneity in animal models achieved by single-cell or single-nucleus RNA sequencing, no research has investigated the transcriptomic profiles of glial cells in the human PNS and spinal cord. Here, we used high-throughput single-nucleus RNA sequencing to map the cellular and molecular heterogeneity of SGCs in the human dorsal root ganglion (DRG) and astrocytes, microglia, and oligodendrocytes in the human spinal cord. To explore the conservation and divergence across species, we compared these human findings with those from mice. Additionally, the expression profiles of risk genes of common DRG and spinal cord diseases in glial cells were compared between humans and mice. As a result, little SGCs heterogeneity was found in both human and mouse DRG. In the human spinal cord, astrocytes, microglia, and oligodendrocytes were respectively divided into six distinct transcriptomic subclusters. In the mouse spinal cord, astrocytes, microglia, and oligodendrocytes were divided into six, five, and six distinct transcriptomic subclusters, respectively. The comparative results revealed substantial heterogeneity in all glial cells between humans and mice. Notably, we also identified transcriptomic heterogeneity in several classical genes and risk genes for neurological disorders across humans and mice. Together, the present data comprehensively profiled glial cell heterogeneity and provides a powerful resource for investigating the cellular basis of glial-related physiological and pathological conditions in peripheral somatosensory system.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Single-nucleus transcriptomic analysis reveals divergence of glial cells in peripheral somatosensory system between human and mouse

Zhang

Wei

Liu

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…They are intercalated in neuropil, myelinated tracts as well as neuronal layers and their morphological and functional diversity is determined by local cues (De Biase et al, 2017;Kapoor et al, 2016;Zheng et al, 2021). In contrast, the density of neurons across brain regions can considerably differ (Keller et al, 2018), depending on the neuron size and spatial organization.…”

Section: Discussionmentioning

confidence: 99%

Microglia form satellites with different neuronal subtypes in the adult murine central nervous system

Bakina

Kettenmann

Nolte

2022

J of Neuroscience Research

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Microglia are the resident immune cells of the central nervous system (CNS) and function as a first line of defense against pathogens, during brain perturbations and in neurodegeneration. They also have important roles during development and for homeostasis in the uncompromised CNS, where they contribute to synaptic plasticity and neuronal function (Colonna & Butovsky, 2017;Kettenmann et al., 2011;Schafer et al., 2012;Tremblay et al., 2011). Microglia originate from the yolk sac and colonize the CNS during early embryonic development. In the mature healthy brain, they are characterized by a distinct ramified morphology with small cell bodies and branched processes that constantly surveil their surrounding environment (Davalos et al., 2005;Kettenmann et al., 2011;Nimmerjahn et al. 2005). Each microglial cell occupies a defined territory and microglial cell bodies are not in direct contact with each other (Lawson et al., 1990). It is well established that microglia represent a phenotypic diversity in terms of number, morphology, activity, and transcriptomics across brain regions in the adult healthy brain (De

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“… 52 , 54 - 56 Despite advancements in technology such as single-cell RNA sequencing, it remains difficult to differentiate between microglia and macrophages that have infiltrated the brain. 28 , 53 , 57 - 59 …”

Section: Innate Immune Responsementioning

confidence: 99%

Inflammation Unleashed in Viral-Induced Epileptogenesis

et al. 2021

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Viral infection of the central nervous system increasingly places people at risk of developing life-threatening and treatment-resistant acute and chronic seizures (epilepsy). The emergence of new human viruses due to ongoing social, political, and ecological changes places people at risk more than ever before. The development of new preventative or curative strategies is critical to address this burden. However, our understanding of the complex relationship between viruses and the brain has been hindered by the lack of animal models that survive the initial infection and are amenable for long-term mechanistic, behavioral, and pharmacological studies in the process of viral-induced epileptogenesis. In this review, we focus on the Theiler’s murine encephalomyelitis virus (TMEV) mouse model of viral infection–induced epilepsy. The TMEV model has a number of important advantages to address the quintessential processes underlying the development of epilepsy following a viral infection, as well as fuel new therapeutic development. In this review, we highlight the contributions of the TMEV model to our current understanding of the relationship between viral infection, inflammation, and seizures.

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Single-cell RNA-seq analysis reveals compartment-specific heterogeneity and plasticity of microglia

Cited by 36 publications

References 40 publications

Single-nucleus transcriptomic analysis reveals divergence of glial cells in peripheral somatosensory system between human and mouse

Single-nucleus transcriptomic analysis reveals divergence of glial cells in peripheral somatosensory system between human and mouse

Microglia form satellites with different neuronal subtypes in the adult murine central nervous system

Inflammation Unleashed in Viral-Induced Epileptogenesis

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