Article
Neurosciences
Yuanyuan Wang, Roxanne V. Kyauk, Yun-An A. Shen, Luke Xie, Mike Reichelt, Han Lin, Zhiyu Jiang, Hai Ngu, Kimberle Shen, Jacob J. Greene, Morgan Sheng, Tracy J. Yuen
Summary: Disability in multiple sclerosis (MS) is partially caused by the failure of remyelination and progressive neurodegeneration. The role of microglia, especially triggering receptor expressed on myeloid cells 2 (TREM2), in remyelination is significant. In this study, using a mouse model of focal demyelination, we found that TREM2 knockout mice had persistent demyelination and subsequent neurodegeneration lasting more than 6 weeks. Furthermore, TREM2 knockout microglia showed defects in migration and phagocytosis of myelin debris.
Article
Cell Biology
Renato Socodato, Tiago O. Almeida, Camila C. Portugal, Evelyn C. S. Santos, Joana Tedim-Moreira, Joao Galvao-Ferreira, Teresa Canedo, Filipa I. Baptista, Ana Magalhaes, Antonio F. Ambrosio, Cord Brakebusch, Boris Rubinstein, Irina S. Moreira, Teresa Summavielle, Ines Mendes Pinto, Joao B. Relvas
Summary: This study demonstrates that Rac1 in microglia is crucial for sensing and interpreting the brain microenvironment, as well as for the communication between microglia and synapses that drives experience-dependent plasticity and cognitive performance.
Article
Cell Biology
Kimberle Shen, Mike Reichelt, Roxanne Kyauk, Hai Ngu, Yun-An A. Shen, Oded Foreman, Zora Modrusan, Brad A. Friedman, Morgan Sheng, Tracy J. Yuen
Summary: The Mertk gene plays a crucial role in microglial activation, phagocytosis, and migration during remyelination, with its deficiency leading to impaired clearance of myelin debris and inhibited remyelination. IFN gamma is identified as a key mediator in the inhibitory effect of myelin debris on remyelination, hindering microglial clearance of myelin debris and oligodendrocyte differentiation.
Article
Neurosciences
Sameera Zia, Brady P. Hammond, Martin Zirngibl, Anastasia Sizov, Charbel S. Baaklini, Sharmistha P. Panda, Madelene F. S. Ho, Kelly V. Lee, Apurba Mainali, Mena K. Burr, Sioned Williams, Andrew V. Caprariello, Christopher Power, Thomas Simmen, Bradley J. Kerr, Jason R. Plemel
Summary: This study investigates the response of microglia during demyelination using a mouse model and in vitro culture system. The results indicate that microglia play multiple roles in the process of demyelination and exhibit a transcriptomic state similar to other neurodegenerative conditions.
MOLECULAR NEURODEGENERATION
(2022)
Article
Multidisciplinary Sciences
Pablo Izquierdo, Hiroko Shiina, Chanawee Hirunpattarasilp, Grace Gillis, David Attwell
Summary: Microglia are immune cells in the central nervous system responsible for phagocytosing redundant synapses and debris. The THIK-1 K+ channels play a crucial role in regulating microglial phagocytosis and synaptic pruning. Changes in THIK-1 expression levels may impact neural circuit function.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Nathaniel G. Jones, Vincent Geoghegan, Gareth Moore, Juliana B. T. Carnielli, Katherine Newling, Felix Calderon, Raquel Gabarro, Julio Martin, Rab K. Prinjha, Inmaculada Rioja, Anthony J. Wilkinson, Jeremy C. Mottram
Summary: Leishmania require the bromodomain-enriched CRKT complex for interpreting histone acetylation marks and maintaining normal gene expression and cellular viability.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Xinyun Chen, Ying Liu, Chen Xu, Lina Ba, Zhuo Liu, Xiuya Li, Jie Huang, Ed Simpson, Hongyu Gao, Dayan Cao, Wei Sheng, Hanping Qi, Hongrui Ji, Maria Sanderson, Chen-Leng Cai, Xiaohui Li, Lei Yang, Jie Na, Kenichi Yamamura, Yunlong Liu, Guoying Huang, Weinian Shou, Ning Sun
Summary: The RNA-binding protein Quaking (QKI) plays a crucial role in cardiac development and contractile physiology through its regulation of alternative splicing in genes involved in Z-disc formation and contractile physiology. Deficiency of QKI results in the failure of cardiomyocytes to mature into functional cells, highlighting its importance in cardiac pathophysiology.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Shenjie Zhong, Haoyi Li, Yun-Sheng Wang, Ying Wang, Guangdong Ji, Hong-Yan Li, Shicui Zhang, Zhenhui Liu
Summary: Bmp8a is a newly-identified positive regulator for antiviral immune responses, which interacts with Alk6a to promote the phosphorylation of Tbk1 and Irf3 through the p38 MAPK pathway, inducing the production of type I interferons to control viral infection.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Cyriel Sebastiaan Olie, Adan Pinto-Fernandez, Andreas Damianou, Iolanda Vendrell, Hailiang Mei, Bianca den Hamer, Erik van der Wal, Jessica C. de Greef, Vered Raz, Benedikt M. Kessler
Summary: The ubiquitin proteasomal system plays a critical role in muscle physiology, but the function of deubiquitinating enzymes (DUBs) in muscle cells remains poorly understood. Through a genetic screen, we discovered that the depletion of USP18, a DUB, affects muscle cell differentiation. USP18 regulates differentiation initiation and maintenance independently of ISG15 and the ISG response. Alterations in gene networks and protein expression profiles were observed in the absence of USP18, leading to disrupted calcium homeostasis and reduced contractile force.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Sol Beccari, Virginia Sierra-Torre, Jorge Valero, Marta Pereira-Iglesias, Mikel Garcia-Zaballa, Federico N. Soria, Laura De Las Heras-garcia, Alejandro Carretero-Guillen, Estibaliz Capetillo-Zarate, Maria Domercq, Paloma R. Huguet, David Ramonet, Ahmed Osman, Wei Han, Cecilia Dominguez, Travis E. Faust, Omar Touzani, Olatz Pampliega, Patricia Boya, Dorothy Schafer, Guillermo Marino, Emmanuelle Canet-Soulas, Klas Blomgren, Ainhoa Plaza-Zabala, Amanda Sierra
Summary: The dysfunction of microglial phagocytosis, resulting in impaired engulfment and degradation, is found in stroke and other brain disorders. This dysfunction is not explained by transcriptional changes but is related to energy depletion triggered by oxygen and nutrient deprivation. Modulating microglial autophagy may be a potential therapeutic strategy for stroke and other brain disorders.
Article
Biochemistry & Molecular Biology
Mona Abdollahi, Margaret Fahnestock
Summary: Nurr1 and BDNF play important roles in cognition, with Nurr1 regulating BDNF in different brain areas. However, Nurr1 does not regulate BDNF in cortical neurons. Treatment with Nurr1 agonist AQ and membrane depolarization increased Nurr1 and BDNF expression in cortical neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nikola Sekulovski, Allison E. Whorton, Mingxin Shi, Kanako Hayashi, James A. MacLean
Summary: Insulin signaling is crucial for the development of preovulatory follicles and progression through the antral stage in mice. Knockout of both INSR and IGF1R results in infertility, defects in ovulation, luteinization, steroidogenesis, and early embryo development due to compromised uterine cell proliferation and decidualization. Additionally, insulin signaling acts downstream of ESR1 and PGR in regulating uterine proliferation and implantation.
Article
Multidisciplinary Sciences
Samantha C. Quintanilla, Neda Habibi Arejan, Parthvi Patel, Cara Boutte
Summary: This study identifies a new polar factor, PlrA, that is responsible for restricting peptidoglycan metabolism at the cell poles in Mycobacterium smegmatis. It is found that only the N-terminal membrane domain of PlrA is necessary for its function. Furthermore, PlrA is shown to regulate the polar foci of the polar growth factor, Wag31.
Article
Immunology
Isabel M. Alonso Bellido, Mercedes Posada-Perez, Francisco Hernandez-Rasco, Sandra Vazquez-Reyes, Maria Cabanillas, Antonio J. Herrera, Sara Bachiller, Jesus Soldan-Hidalgo, Ana M. Espinosa-Oliva, Bertrand Joseph, Rocio M. de Pablos, Jose L. Venero, Rocio Ruiz
Summary: The study aims to investigate the role of Caspase-3 in neurogenesis-related microglial functions. Using Caspase-3 conditional knockout mice, it was found that the reduction of Caspase-3 led to decreased microglia and neurogenic neurons in the hippocampus, as well as a lower phagocytic capacity of microglia. Behavioral analysis also showed impaired memory and learning in the absence of Caspase-3. These findings highlight the essential role of Caspase-3 in microglial function and the importance of a specific microglial phenotype in the maintenance of adult hippocampal neurogenesis.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Review
Immunology
Junqiu Jia, Lixuan Yang, Yan Chen, Lili Zheng, Yanting Chen, Yun Xu, Meijuan Zhang
Summary: Microglia play diverse roles in the pathogenesis of ischemic stroke, with their phagocytic properties being a subject of debate. Understanding the precise mechanisms of microglial phagocytosis after stroke may help in developing regulatory molecules that promote inflammation resolution without harming functional cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Peng Zhang, Dandan He, Yi Xu, Jiakai Hou, Bih-Fang Pan, Yunfei Wang, Tao Liu, Christel M. Davis, Erik A. Ehli, Lin Tan, Feng Zhou, Jian Hu, Yonghao Yu, Xi Chen, Tuan M. Nguyen, Jeffrey M. Rosen, David H. Hawke, Zhe Ji, Yiwen Chen
NATURE COMMUNICATIONS
(2017)
Article
Biology
Xin Zhou, Seula Shin, Chenxi He, Qiang Zhang, Matthew N. Rasband, Jiangong Ren, Congxin Dai, Rocio Zorrilla-Veloz, Takashi Shingu, Liang Yuan, Yunfei Wang, Yiwen Chen, Fei Lan, Jian Hu
Summary: This study reveals the crucial role of Qki in controlling cholesterol biosynthesis in the central nervous system, which is essential for myelinogenesis. Depletion of Qki results in reduced cholesterol concentration in the brain, impairing proper myelin assembly.
Article
Oncology
Andrew Fedoriw, Leilei Shi, Shane O'Brien, Kimberly N. Smitheman, Yunfei Wang, Jiakai Hou, Christian Sherk, Satyajit Rajapurkar, Jenny Laraio, Leila J. Williams, Chunyu Xu, Guangchun Han, Qin Feng, Mark T. Bedford, Linghua Wang, Olena Barbash, Ryan G. Kruger, Patrick Hwu, Helai P. Mohammad, Weiyi Peng
Summary: Protein arginine methyltransferases play crucial roles in cancer progression, with inhibition of type I PRMTs increasing T-cell infiltration and inducing durable anti-tumor responses in immunotherapy.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Medicine, Research & Experimental
Amber Hickman, Joost Koetsier, Trevin Kurtanich, Michael C. Nielsen, Glenn Winn, Yunfei Wang, Salah-Eddine Bentebibel, Leilei Shi, Simone Punt, Leila Williams, Cara Haymaker, Charles B. Chesson, Faisal Fa'ak, Ana L. Dominguez, Richard Jones, Isere Kuiatse, Amy R. Caivano, Sayadeth Khounlo, Navin D. Warier, Upendra Marathi, Robert Market, Ronald J. Biediger, John W. Craft, Patrick Hwu, Michael A. Davies, Darren G. Woodside, Peter Vanderslice, Adi Diab, Willem W. Overwijk, Yared Hailemichael
Summary: The small-molecule activator 7HP349 enhances the localization of tumor-specific T cells to tumors and improves antitumor response, with combinatorial treatment synergizing with neutrophils in inducing cancer regression.
JOURNAL OF CLINICAL INVESTIGATION
(2022)