Article
Immunology
I. Y. Quiroga, A. E. Cruikshank, M. L. Bond, K. S. M. Reed, B. A. Evangelista, J. H. Tseng, J. Ragusa, R. B. Meeker, H. Won, S. Cohen, T. J. Cohen, D. H. Phanstiel
Summary: This study found that human induced pluripotent stem cell (hIPSC)-derived microglia (IMGL) is the in vitro cell model that best resembles primary microglia in the AD brain. Surprisingly, synthetic A beta does not trigger a significant transcriptional response in any of the cellular models analyzed, while bacterial LPS and INF gamma can activate microglia and induce transcriptional changes similar to those observed in microglia detected in AD brains.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Neurosciences
Omkar L. Patkar, Melanie Caruso, Ngari Teakle, Sahar Keshvari, Stephen J. Bush, Clare Pridans, Arnauld Belmer, Kim M. Summers, Katharine M. Irvine, David A. Hume
Summary: Mutations in the human CSF1R gene have been associated with neurodegenerative diseases. Results from rat models with Csf1r mutations show reduced fiber tracts and microglial markers, with minimal impact on other neuronal markers. Defects in dendritic arborization and expression of specific neural cell adhesion molecules were also observed. These findings suggest that microglia may play a significant role in brain development, while CSF1R haploinsufficiency is unlikely to cause leukoencephalopathy.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biotechnology & Applied Microbiology
Daniel C. Shippy, Jyoti J. Watters, Tyler K. Ulland
Summary: The study revealed that AD activates multiple signaling pathways that regulate numerous genes in microglia, contributing to Aβ phagocytosis and neuroinflammation. These findings identified several regulatory factors and biomarkers in microglia, which could be beneficial for further comprehension of AD neuropathology.
Article
Immunology
Kate M. Sutton, Katrina M. Morris, Dominika Borowska, Helen Sang, Pete Kaiser, Adam Balic, Lonneke Vervelde
Summary: This study characterized the cells of the mononuclear phagocyte system (MPS) in the chicken spleen using CSF1R-reporter transgenic chickens. Different subsets of macrophages and conventional dendritic cells were identified in the chicken spleen, showing diverse functions and expression profiles that are essential for future research on immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Meng Liy Pan, Nur Nabilah Ahmad Puzi, Yin Yin Ooi, Rajesh Ramasamy, Sharmili Vidyadaran
Summary: The latest research shows that microglia phenotype is not limited to the binary states of "resting" and "activated", but exhibits wide diversity. Testing different stimulation protocols for BV2 microglia, we found differences in the response of the cells in terms of intracellular ROS, nitric oxide, CD40 expression, and migratory capacity.
Article
Biochemistry & Molecular Biology
Peter Wieghofer, Nora Hagemeyer, Roman Sankowski, Anja Schlecht, Ori Staszewski, Lukas Amann, Markus Gruber, Jana Koch, Annika Hausmann, Peipei Zhang, Stefaniya Boneva, Takahiro Masuda, Ingo Hilgendorf, Tobias Goldmann, Chotima Boettcher, Josef Priller, Fabio M. Rossi, Clemens Lange, Marco Prinz
Summary: The study identified different transcriptional states of myeloid subsets in the eye, particularly disease-specific macrophage subpopulations with distinct molecular signatures during choroidal neovascularization, a hallmark of neovascular age-related macular degeneration (AMD). These findings provide new insights into the innate immune system in the eye and potential therapeutic targets for ophthalmological diseases.
Article
Biochemistry & Molecular Biology
Vladimir N. Babenko, Galina T. Shishkina, Dmitriy A. Lanshakov, Ekaterina Sukhareva, Nikolay N. Dygalo
Summary: In this study, transcriptome analysis was performed in the hippocampus 24 h after lipopolysaccharide (LPS) administration. Glial-specific genes were observed, which accounted for two-thirds of all differentially expressed genes (DEGs). Differential alternative splicing (DAS) analysis revealed the most numerous DAS events in astrocytes, while microglial DEGs were the most abundant in the LPS group. Additionally, distinct major isoform switching in the Ptbp1 gene was observed, with skipping of exon 8 in the LPS group. The study suggests that alternative splicing plays an immune modulating role in the brain.
Article
Cell Biology
Jiwei Jiang, Wenyi Li, Xiaohong Wang, Zhongli Du, Jinlong Chen, Yaou Liu, Wei Li, Zhonghua Lu, Yanli Wang, Jun Xu
Summary: This study describes two novel heterozygous splicing variants of the CSF1R gene in two unrelated Han Chinese families with CSF1R-microglial encephalopathy. The findings highlight the value of pCASL for early detection of this disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Yan Mei, Xiumei Wang, Ji Zhang, Dan Liu, Junjie He, Chunliu Huang, Jing Liao, Yingzhao Wang, Yongyi Feng, Hongyu Li, Xiuying Liu, Lingdan Chen, Wei Yi, Xi Chen, Hong-Min Bai, Xinyu Wang, Yiyi Li, Lixiang Wang, Zhigang Liang, Xianwen Ren, Li Qiu, Yuan Hui, Qingling Zhang, Qibin Leng, Jun Chen, Guangshuai Jia
Summary: By analyzing the single-cell RNA sequencing and spatial transcriptomics of patients with glioblastoma multiforme (GBM) treated with neoadjuvant anti-PD-1 therapy, researchers identified a subpopulation of monocyte-derived tumor-associated macrophages that highly express the immunosuppressive SIGLEC9 gene and are resistant to anti-PD-1 treatment. Deletion of Siglece (murine homolog) resulted in suppressed tumor growth and improved survival in mouse models by activating CD4(+) T cells and CD8(+) T cells. Furthermore, Siglece deletion synergized with anti-PD-1/PD-L1 treatment to enhance antitumor efficacy.
Article
Clinical Neurology
Philip W. Tipton, Daniel Kenney-Jung, Beth K. Rush, Erik H. Middlebrooks, David Nascene, Balvindar Singh, Shernan Holtan, Ernesto Ayala, Daniel F. Broderick, Troy Lund, Zbigniew K. Wszolek
Summary: The study found that HSCT treatment for CSF1R-related leukoencephalopathy can stabilize the disease in some patients, but there is variability in patient responsiveness. Therefore, measures of disease heterogeneity and severity should be considered when evaluating a patient's candidacy for transplant.
MOVEMENT DISORDERS
(2021)
Article
Immunology
Baoying Cheng, Xin Li, Kai Dai, Shengshun Duan, Zhouyi Rong, Yingmin Chen, Liangcheng Lu, Zhaoji Liu, Xiaohua Huang, Huaxi Xu, Yun-Wu Zhang, Honghua Zheng
Summary: TREM2 and CSF1R interact directly in microglia cells, modulating their expression levels. Administration of CSF1 partially restores the survival ability of Trem2-deficient microglia, showing potential therapeutic intervention in TREM2 variant-bearing patients with a high risk of Alzheimer's disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Menglong Feng, Xiaoqing Zhou, Yaqin Hu, Juhong Zhang, Ting Yang, Zhiji Chen, Wei Yuan
Summary: This study reveals the differential m6A methylation patterns in the cochlear tissues of age-related hearing loss (ARHL) mice and identifies m6A methylation regulators that are downregulated in ARHL. The study also identifies genes with differential m6A methylation and significant differences in mRNA expression in the cochlear tissues of ARHL mice, which are mainly enriched in the PI3K-AKT signaling pathway. These findings provide a theoretical basis for further understanding the pathogenesis of ARHL and potential therapeutic strategies.
Article
Cell & Tissue Engineering
Yijing Su, Yi Zhou, Mariko L. Bennett, Shiying Li, Marc Carceles-Cordon, Lu Lu, Sooyoung Huh, Dennisse Jimenez-Cyrus, Benjamin C. Kennedy, Sudha K. Kessler, Angela N. Viaene, Ingo Helbig, Xiaosong Gu, Joel E. Kleinman, Thomas M. Hyde, Daniel R. Weinberger, David W. Nauen, Hongjun Song, Guo-li Ming
Summary: This study used single-nucleus RNA sequencing to analyze the transcriptome atlas of glia in the human hippocampus. The results revealed distinct molecular signatures of glial subpopulations and their associations with physiological functions, age-dependent changes, and relevance to diseases such as Alzheimer's disease. Furthermore, the study characterized the spatiotemporal heterogeneity of certain astrocyte subpopulations and identified dysregulated genes and pathological processes in specific glial subpopulations in Alzheimer's disease. The findings significantly contribute to our understanding of human glial diversity and the dysregulation in Alzheimer's disease, as well as provide a reference atlas for stem cell-based glial differentiation.
Article
Neurosciences
Dave E. Marzan, Valerie Brugger-Verdon, Brian L. West, Shane Liddelow, Jayshree Samanta, James L. Salzer
Summary: The activated microglia play a crucial role in demyelination, with CSF1 signaling being implicated in these events.
Article
Immunology
Lan Wang, Danfeng Zhao, Huan Wang, Lele Wang, Xiaohui Liu, Haiyan Zhang
Summary: FPS-ZM1 was found to inhibit LPS-induced microglial inflammation, with the possible mechanism involving the JAK/STAT signaling pathway. The study demonstrated the anti-inflammatory effects of FPS-ZM1 in both in vivo and in vitro models.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Critical Care Medicine
Zoe M. Tapp, Julia E. Kumar, Kristina G. Witcher, Ravitej R. Atluri, John A. Velasquez, Shane M. O'Neil, Julia E. Dziabis, Chelsea E. Bray, John F. Sheridan, Jonathan P. Godbout, Olga N. Kokiko-Cochran
JOURNAL OF NEUROTRAUMA
(2020)
Article
Biochemistry & Molecular Biology
Damon J. DiSabato, Daniel P. Nemeth, Xiaoyu Liu, Kristina G. Witcher, Shane M. O'Neil, Braedan Oliver, Chelsea E. Bray, John F. Sheridan, Jonathan P. Godbout, Ning Quan
Summary: Chronic stress can lead to psychiatric disorders such as anxiety and depression. Inflammatory effects of stress, particularly mediated by IL-1 signaling in hippocampal neurons, play a crucial role in modulating social behavior and cognitive function. Targeting IL-1R1 signaling in glutamatergic neurons may provide a novel therapeutic approach for alleviating stress-induced behavioral deficits.
MOLECULAR PSYCHIATRY
(2021)
Article
Neurosciences
Kristina G. Witcher, Chelsea E. Bray, Titikorn Chunchai, Fangli Zhao, Shane M. O'Neil, Alan J. Gordillo, Warren A. Campbell, Daniel B. McKim, Xiaoyu Liu, Julia E. Dziabis, Ning Quan, Daniel S. Eiferman, Andy J. Fischer, Olga N. Kokiko-Cochran, Candice Askwith, Jonathan P. Godbout
Summary: Traumatic brain injury can lead to significant neuropsychiatric problems and neurodegenerative pathologies that last for years. This study showed that microglia play a crucial role in acute and chronic stages of TBI, influencing inflammation and neuropathology development, which in turn affect neuronal homeostasis and behavioral outcomes.
JOURNAL OF NEUROSCIENCE
(2021)