Review
Immunology
Andres Vidal-Itriago, Rowan A. W. Radford, Jason A. A. Aramideh, Cindy Maurel, Natalie M. M. Scherer, Emily K. K. Don, Albert Lee, Roger S. S. Chung, Manuel B. B. Graeber, Marco Morsch
Summary: Microglia, originating from mesoderm, play key roles in the development, homeostasis, and innate immunity of the central nervous system (CNS). Their diverse morphological characteristics are closely related to their wide range of functions. However, our knowledge of the morphophysiological attributes and interactions with neurons of microglia is limited. Exploring the correlation between microglial shape and function is a current challenge and opportunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Rei Mishima, Masayuki Taniguchi, Kazutoshi Matsushita, Bowen Tian, Tomoyuki Furuyashiki
Summary: Using single-cell RNA sequencing, distinct microglial subpopulations with different transcriptome signatures were identified in the resting brain. The distribution of these subpopulations varied across brain regions, particularly between the cerebral cortices and the hypothalamus. Lipopolysaccharide and chronic social defeat stress, both involving the innate immune receptor TLR4, upregulated marker genes of selective microglial subpopulations. These findings highlight the contribution of microglial subpopulations to the heterogeneity of microglial transcriptome and responsiveness in different brain regions.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2023)
Review
Clinical Neurology
Sandra Amor, Niamh B. McNamara, Emma Gerrits, Manuel C. Marzin, Susanne M. Kooistra, Veronique E. Miron, Erik Nutma
Summary: Microglia, the resident myeloid cells in the central nervous system, have diverse roles in maintaining homeostasis, responding to diseases, and promoting repair. Advances in technology have revealed the complexity of microglial functions in white matter health. Additionally, microglia are intricately linked to various diseases and disease mechanisms.
ACTA NEUROPATHOLOGICA
(2022)
Article
Cell Biology
Jingyu Wang, Lintao Xu, Weiwei Lin, Yin Yao, Heyangzi Li, Gerong Shen, Xi Cao, Ning He, Jun Chen, Jue Hu, Mingzhi Zheng, Xinghui Song, Yuemin Ding, Yueliang Shen, Jinjie Zhong, Lin-lin Wang, Ying-ying Chen, Yongjian Zhu
Summary: Neuroinflammation is an important pathological process in spinal cord injury (SCI), and repopulation of microglia has been shown to aid in recovery. However, the origin and regulatory factors of microglia repopulation after SCI are still unknown. In this study, researchers used single-cell RNA sequencing to study the immune cells during different phases of SCI in mice. They found that residual microglia were the source of repopulated microglia after SCI, and Hif1 alpha played a role in their proliferation. These findings provide new insights into the immune heterogeneity in SCI and suggest that targeting Hif1 alpha may promote axon regeneration and functional recovery.
CELL DEATH & DISEASE
(2022)
Article
Immunology
Moein Yaqubi, Adam M. R. Groh, Marie-France Dorion, Elia Afanasiev, Julia Xiao Xuan Luo, Hadi Hashemi, Sarthak Sinha, Nicholas W. Kieran, Manon Blain, Qiao-Ling Cui, Jeff Biernaskie, Myriam Srour, Roy Dudley, Jeffery A. Hall, Joshua A. Sonnen, Nathalie Arbour, Alexandre Prat, Jo Anne Stratton, Jack Antel, Luke M. Healy
Summary: This study aimed to characterize the transcriptional landscape of ex vivo human microglia at different developmental ages. The results showed that pre-natal microglia have a distinct transcriptional signature and an upregulation of phagocytic pathways. Adult microglia exhibit a more pro-inflammatory signature and are more immune responsive. The study also indicated that the transcriptional signatures of microglia are in response to a changing brain microenvironment and not predetermined developmental states.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Multidisciplinary Sciences
Di Zhang, Yanxiang Deng, Petra Kukanja, Eneritz Agirre, Marek Bartosovic, Mingze Dong, Cong Ma, Sai Ma, Graham Su, Shuozhen Bao, Yang Liu, Yang Xiao, Gorazd B. Rosoklija, Andrew J. Dwork, J. John Mann, Kam W. Leong, Maura Boldrini, Liya Wang, Maximilian Haeussler, Benjamin J. Raphael, Yuval Kluger, Goncalo Castelo-Branco, Rong Fan
Summary: Emerging spatial technologies such as spatial transcriptomics and spatial epigenomics have become powerful tools in profiling cellular states in tissue contexts. However, current methods only capture one layer of omics information at a time, limiting the examination of mechanistic relationships in molecular biology. In this study, two technologies are presented for joint profiling of the epigenome and transcriptome at a genome-wide, spatially resolved, and near-single-cell resolution. These technologies provide new insights into spatial epigenetic priming, differentiation, and gene regulation within tissue architecture.
Article
Cell Biology
Wei Wang, Mengdi Wang, Meng Yang, Bo Zeng, Wenying Qiu, Qiang Ma, Xiaoxi Jing, Qianqian Zhang, Bosong Wang, Chonghai Yin, Jiyao Zhang, Yuxin Ge, Yufeng Lu, Weizhi Ji, Qian Wu, Chao Ma, Xiaoqun Wang
Summary: This study investigates the cellular heterogeneity and molecular characteristics of the hippocampi in macaques and aged humans using droplet-based single-nucleus RNA sequencing (snRNA-seq). The findings reveal the dynamics of the neurogenic lineage and the diversity of astrocytes and microglia in the hippocampus. Primate-specific markers are identified and their functions are validated. Additionally, active astrocytes and microglia with proinflammatory responses are observed in aged samples, suggesting their contribution to the decrease and variability of adult hippocampal neurogenesis.
Review
Cell Biology
Jae Lee, Sung Wook Kim, Kyong-Tai Kim
Summary: In this review, the latest research on the intra- and inter-regional heterogeneity of astrocytes and microglia in the brain is summarized, highlighting their potential applications in aging and neurodegenerative diseases.
Article
Multidisciplinary Sciences
Yanping Liu, Yufei Wang, Lu Yang, Feng Sun, Sheng Li, Yequan Wang, Guo-An Zhang, Tingting Dong, Lei-Lei Zhang, Wanglin Duan, Xiaojun Zhang, Wen Cui, Su Chen
Summary: Histone H2B is mainly degraded through the proteasome-mediated pathway, with the lysine-120 site of H2B essential for its degradation. The nucleolus may play a role in H2B degradation, providing a novel mechanism for the regulation of H2B degradation.
Article
Clinical Neurology
Allison R. Hanaford, Asheema Khanna, Vivian Truong, Katerina James, Yihan Chen, Michael Mulholland, Bernhard Kayser, Ryan W. Liao, Margaret Sedensky, Phil Morgan, Nathan Baerchst, Vandana Kalia, Surojit Sarkar, Simon C. Johnson
Summary: Subacute necrotizing encephalopathy, also known as Leigh syndrome (LS), is a common pediatric presentation of genetic mitochondrial disease. LS affects multiple systems and causes severe neurological, metabolic, and musculoskeletal symptoms. Recent research has found that high-dose pexidartinib, a CSF1R inhibitor, can prevent LS CNS lesions and systemic disease. This study focuses on the role of microglia and peripheral macrophages in the pathogenesis of LS.
Review
Oncology
Takahiro Masuda, Lukas Amann, Marco Prinz
Summary: This mini-review provides an overview of the current knowledge on the ontogenetic relationship and underlying mechanism for the establishment of CNS macrophages, highlighting their comparison with microglia.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Kazuyuki Takata, Florent Ginhoux, Shun Shimohama
Summary: Microglia are specialized macrophages in the central nervous system that play key roles in brain immunity, development, and homeostasis. Recent advances in single-cell and single-nucleus transcriptomic technologies have revealed the heterogeneity of microglia and their involvement in brain pathologies, including Alzheimer's disease. Understanding microglial biology at the single-cell level may lead to new therapeutic targets for treating neuroinflammatory conditions like AD.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Clinical Neurology
Zhijuan Cao, Sean S. Harvey, Terrance Chiang, Aulden G. Foltz, Alex G. Lee, Michelle Y. Cheng, Gary K. Steinberg
Summary: This study investigated the spatiotemporal changes in the secondary degenerative thalamus post-stroke, revealing early microglial activation and later neurodegeneration. Transcriptome analysis at PD28 showed a higher number of differentially expressed genes in the thalamus, with neuroinflammation being the top activated pathway and microglia the most enriched cell type. Additionally, a unique subtype of microglia (CD11c(+)) with features of neurodegenerative disease-associated microglia was identified in the degenerative thalamus after stroke.
Article
Biochemistry & Molecular Biology
Masahiro Nakano, Mineto Ota, Yusuke Takeshima, Yukiko Iwasaki, Hiroaki Hatano, Yasuo Nagafuchi, Takahiro Itamiya, Junko Maeda, Ryochi Yoshida, Saeko Yamada, Aya Nishiwaki, Haruka Takahashi, Hideyuki Takahashi, Yuko Akutsu, Takeshi Kusuda, Hiroyuki Suetsugu, Lu Liu, Kwangwoo Kim, Xianyong Yin, So-Young Bang, Yong Cui, Hye-Soon Lee, Hirofumi Shoda, Xuejun Zhang, Sang-Cheol Bae, Chikashi Terao, Kazuhiko Yamamoto, Tomohisa Okamura, Kazuyoshi Ishigaki, Keishi Fujio
Summary: This study conducted a large-scale transcriptome analysis to understand the dysregulated gene expression patterns in systemic lupus erythematosus (SLE). The researchers identified cell-type-specific transcriptomic signatures associated with disease establishment and exacerbation. The study suggested the clinical value of disease-activity signatures in predicting organ involvement and therapeutic responses.
Article
Biotechnology & Applied Microbiology
Marek Bartosovic, Mukund Kabbe, Goncalo Castelo-Branco
Summary: An improved method for single-cell analysis of histone modifications was applied to the mouse brain, combining CUT&Tag technology with droplet-based single-cell library preparation to produce high-quality data. The results provided unique insights into epigenomic landscapes in the central nervous system at single-cell resolution, highlighting the potential of this method for studying chromatin modifications and transcription factor occupancy.
NATURE BIOTECHNOLOGY
(2021)
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.