Glia最新文献 - Book学术

R-Ras1 and R-Ras2 regulate mature oligodendrocyte subpopulations. R-Ras1和R-Ras2调控成熟的少突胶质细胞亚群。

IF 5.4 2区医学

Glia Pub Date : 2024-11-19 DOI: 10.1002/glia.24643

Berta Alcover-Sanchez, Gonzalo Garcia-Martin, Víctor Paleo-García, Ana Quintas, Ana Dopazo, Agnès Gruart, José María Delgado-García, Pedro de la Villa, Francisco Wandosell, Marta P Pereira, Beatriz Cubelos

{"title":"R-Ras1 and R-Ras2 regulate mature oligodendrocyte subpopulations.","authors":"Berta Alcover-Sanchez, Gonzalo Garcia-Martin, Víctor Paleo-García, Ana Quintas, Ana Dopazo, Agnès Gruart, José María Delgado-García, Pedro de la Villa, Francisco Wandosell, Marta P Pereira, Beatriz Cubelos","doi":"10.1002/glia.24643","DOIUrl":"https://doi.org/10.1002/glia.24643","url":null,"abstract":"In the mammalian central nervous system, axonal myelination, executed by mature oligodendrocytes (MOLs), enables rapid neural transmission. Conversely, myelin deficiencies are hallmark features of multiple sclerosis, optic neuromyelitis, and some leukodystrophies. Recent studies have highlighted that MOLs are heterogeneous; however, how MOL subpopulations are specified and balanced in physiological settings is poorly understood. Previous works have demonstrated an essential role of the small GTPases R-Ras1 and R-Ras2 in the survival and myelination of oligodendrocytes. In this study, we aimed to determine how R-Ras1 and R-Ras2 contribute to the heterogeneity of MOL subpopulations. Our results evidence that R-Ras1 and R-Ras2 affect specification into the distinct subpopulations MOL1, MOL2, and MOL5/6, which in turn vary in their dependence of these GTPases. In R-Ras1 and/or R-Ras2 mutant mice, we observed an increase in the MOL1 subpopulation and a decrease in the MOL2 and MOL5/6 subpopulations. We identified R-Ras1 and R-Ras2 as key elements in balancing the heterogeneity of MOLs. Our results contribute to the understanding of the molecular mechanisms underlying the heterogeneity of MOLs and the myelination processes, which is crucial for innovating regenerative therapies for nervous system disorders.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

All the single cells: Single-cell transcriptomics/epigenomics experimental design and analysis considerations for glial biologists. 所有单细胞神经胶质生物学家的单细胞转录组学/表观组学实验设计和分析注意事项。

IF 5.4 2区医学

Glia Pub Date : 2024-11-19 DOI: 10.1002/glia.24633

Katherine E Prater, Kevin Z Lin

{"title":"All the single cells: Single-cell transcriptomics/epigenomics experimental design and analysis considerations for glial biologists.","authors":"Katherine E Prater, Kevin Z Lin","doi":"10.1002/glia.24633","DOIUrl":"https://doi.org/10.1002/glia.24633","url":null,"abstract":"Single-cell transcriptomics, epigenomics, and other 'omics applied at single-cell resolution can significantly advance hypotheses and understanding of glial biology. Omics technologies are revealing a large and growing number of new glial cell subtypes, defined by their gene expression profile. These subtypes have significant implications for understanding glial cell function, cell-cell communications, and glia-specific changes between homeostasis and conditions such as neurological disease. For many, the training in how to analyze, interpret, and understand these large datasets has been through reading and understanding literature from other fields like biostatistics. Here, we provide a primer for glial biologists on experimental design and analysis of single-cell RNA-seq datasets. Our goal is to further the understanding of why decisions are made about datasets and to enhance biologists' ability to interpret and critique their work and the work of others. We review the steps involved in single-cell analysis with a focus on decision points and particular notes for glia. The goal of this primer is to ensure that single-cell 'omics experiments continue to advance glial biology in a rigorous and replicable way.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astrocytic NHERF-1 Increases Seizure Susceptibility by Inhibiting Surface Expression of TREK-1. 星形胶质细胞 NHERF-1 通过抑制 TREK-1 的表面表达增加癫痫易感性

IF 5.4 2区医学

Glia Pub Date : 2024-11-14 DOI: 10.1002/glia.24644

Yeonju Bae, Soomin Lee, Ajung Kim, Shinae Lee, Seong-Seop Kim, Sunyoung Park, Junyeol Noh, Kanghyun Ryoo, Gwan-Su Yi, Jae-Yong Park, Eun Mi Hwang

{"title":"Astrocytic NHERF-1 Increases Seizure Susceptibility by Inhibiting Surface Expression of TREK-1.","authors":"Yeonju Bae, Soomin Lee, Ajung Kim, Shinae Lee, Seong-Seop Kim, Sunyoung Park, Junyeol Noh, Kanghyun Ryoo, Gwan-Su Yi, Jae-Yong Park, Eun Mi Hwang","doi":"10.1002/glia.24644","DOIUrl":"10.1002/glia.24644","url":null,"abstract":"Mature hippocampal astrocytes exhibit a linear current-to-voltage (I-V) K+ membrane conductance called passive conductance. It is estimated to enable astrocytes to keep potassium homeostasis in the brain. We previously reported that the TWIK-1/TREK-1 heterodimeric channels are crucial for astrocytic passive conductance. However, the regulatory mechanism of these channels by other binding proteins remains elusive. Here, we identified Na+/H+ exchange regulator-1 (NHERF-1), a protein highly expressed in astrocytes, as a novel interaction partner for these channels. NHERF-1 endogenously bound to TWIK-1/TREK-1 in hippocampal cultured astrocytes. When NHERF-1 is overexpressed or silenced, surface expression and activity of TWIK-1/TREK-1 heterodimeric channels are inhibited or enhanced, respectively. Furthermore, we confirmed that reduced astrocytic passive conductance by NHERF-1 overexpressing in the hippocampus increases kainic acid (KA)-induced seizure sensitivity. Taken together, these results suggest that NHERF-1 is a key regulator of TWIK-1/TREK-1 heterodimeric channels in astrocytes and suppression of TREK-1 surface expression by NHERF-1 increases KA-induced seizure susceptibility via reduction of astrocytic passive conductance.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aquaporin-4 activation facilitates glymphatic system function and hematoma clearance post-intracerebral hemorrhage. 激活Aquaporin-4有助于脑出血后的肾上腺系统功能和血肿清除。

IF 5.4 2区医学

Glia Pub Date : 2024-11-12 DOI: 10.1002/glia.24639

Wenchao Chen, Chuntian Liang, Shasha Peng, Shuangjin Bao, Fang Xue, Xia Lian, Yinghong Liu, Gaiqing Wang

{"title":"Aquaporin-4 activation facilitates glymphatic system function and hematoma clearance post-intracerebral hemorrhage.","authors":"Wenchao Chen, Chuntian Liang, Shasha Peng, Shuangjin Bao, Fang Xue, Xia Lian, Yinghong Liu, Gaiqing Wang","doi":"10.1002/glia.24639","DOIUrl":"https://doi.org/10.1002/glia.24639","url":null,"abstract":"Efficient clearance of hematomas is crucial for improving clinical outcomes in patients with intracerebral hemorrhage (ICH). The glymphatic system, facilitated by aquaporin-4 (AQP4), plays a crucial role in cerebrospinal fluid (CSF) entry and metabolic waste clearance. This study examined the role of the glymphatic system in ICH pathology, with a focus on AQP4. Collagenase-induced ICH models were established, with AQP4 expression regulated through mifepristone as an agonist, TGN-020 as an inhibitor, and Aqp4 gene knockout. Fluorescence tracing and multimodal magnetic resonance imaging (MRI) were employed to observe glymphatic system functionality, hematoma, and edema volumes. Neurological deficit scoring was performed using the modified Garcia Scale. AQP4 expression was quantified using RT-qPCR and Western blotting, and cellular localization was explored using immunofluorescence. The brain tissue sections were examined for neuronal morphology, degenerative changes, and iron deposition. Three days post-ICH, the AQP4 agonist group showed increased AQP4 protein expression and perivascular polarization, decreased hemoglobin levels, and reduced iron deposition. Conversely, the inhibition group exhibited contrasting trends. AQP4 activation improved glymphatic system function, leading to a wider distribution, improved neurological function, and reduced hematoma. Pharmacological inhibition and genetic knockout of AQP4 have opposing effects. The glymphatic system, facilitated by AQP4, plays a crucial role in hematoma clearance following cerebral hemorrhage. Upregulation of AQP4 improves glymphatic system function, facilitates hematoma clearance, and promotes brain tissue recovery.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

YAP and TAZ regulate remyelination in the central nervous system YAP和TAZ调节中枢神经系统的髓鞘再生

IF 6.2 2区医学

Glia Pub Date : 2023-09-19 DOI: 10.1002/glia.24467

Jiayue Hong, Julia M. Kirkland, Jenica Acheta, Leandro N. Marziali, Brianna Beck, Haley Jeanette, Urja Bhatia, Grace Davis, Jacob Herron, Clémence Roué, Charly Abi-Ghanem, M. Laura Feltri, Kristen L. Zuloaga, Marie E. Bechler, Yannick Poitelon, Sophie Belin

{"title":"YAP and TAZ regulate remyelination in the central nervous system","authors":"Jiayue Hong, Julia M. Kirkland, Jenica Acheta, Leandro N. Marziali, Brianna Beck, Haley Jeanette, Urja Bhatia, Grace Davis, Jacob Herron, Clémence Roué, Charly Abi-Ghanem, M. Laura Feltri, Kristen L. Zuloaga, Marie E. Bechler, Yannick Poitelon, Sophie Belin","doi":"10.1002/glia.24467","DOIUrl":"10.1002/glia.24467","url":null,"abstract":"Myelinating cells are sensitive to mechanical stimuli from their extracellular matrix. Ablation of YAP and TAZ mechanotransducers in Schwann cells abolishes the axon–Schwann cell recognition, myelination, and remyelination in the peripheral nervous system. It was unknown if YAP and TAZ are also required for myelination and remyelination in the central nervous system. Here we define the importance of oligodendrocyte (OL) YAP and TAZ in vivo, by specific deletion in oligodendroglial cells in adult OLs during myelin repair. Blocking YAP and TAZ expression in OL lineage cells did not affect animal viability or any major defects on OL maturation and myelination. However, using a mouse model of demyelination/remyelination, we demonstrate that YAP and TAZ modulate the capacity of OLs to remyelinate axons, particularly during the early stage of the repair process, when OL proliferation is most important. These results indicate that YAP and TAZ signaling is necessary for effective remyelination of the mouse brain.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 1","pages":"156-166"},"PeriodicalIF":6.2,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10313067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel method of isolating nuclei of human oligodendrocyte precursor cells reveals substantial developmental changes in gene expression and H3K27ac histone modification 分离人少突胶质前体细胞细胞核的新方法揭示了基因表达和H3K27ac组蛋白修饰的实质性发育变化

IF 6.2 2区医学

Glia Pub Date : 2023-09-15 DOI: 10.1002/glia.24462

Alexey Kozlenkov, Ramu Vadukapuram, Ping Zhou, Peter Fam, Michael Wegner, Stella Dracheva

{"title":"Novel method of isolating nuclei of human oligodendrocyte precursor cells reveals substantial developmental changes in gene expression and H3K27ac histone modification","authors":"Alexey Kozlenkov, Ramu Vadukapuram, Ping Zhou, Peter Fam, Michael Wegner, Stella Dracheva","doi":"10.1002/glia.24462","DOIUrl":"10.1002/glia.24462","url":null,"abstract":"Oligodendrocyte precursor cells (OPCs) generate differentiated mature oligodendrocytes (MOs) during development. In adult brain, OPCs replenish MOs in adaptive plasticity, neurodegenerative disorders, and after trauma. The ability of OPCs to differentiate to MOs decreases with age and is compromised in disease. Here we explored the cell specific and age-dependent differences in gene expression and H3K27ac histone mark in these two cell types. H3K27ac is indicative of active promoters and enhancers. We developed a novel flow-cytometry-based approach to isolate OPC and MO nuclei from human postmortem brain and profiled gene expression and H3K27ac in adult and infant OPCs and MOs genome-wide. In adult brain, we detected extensive H3K27ac differences between the two cell types with high concordance between gene expression and epigenetic changes. Notably, the expression of genes that distinguish MOs from OPCs appears to be under a strong regulatory control by the H3K27ac modification in MOs but not in OPCs. Comparison of gene expression and H3K27ac between infants and adults uncovered numerous developmental changes in each cell type, which were linked to several biological processes, including cell proliferation and glutamate signaling. A striking example was a subset of histone genes that were highly active in infant samples but fully lost activity in adult brain. Our findings demonstrate a considerable rearrangement of the H3K27ac landscape that occurs during the differentiation of OPCs to MOs and during postnatal development of these cell types, which aligned with changes in gene expression. The uncovered regulatory changes justify further in-depth epigenetic studies of OPCs and MOs in development and disease.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 1","pages":"69-89"},"PeriodicalIF":6.2,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human iPSC-derived endothelial cells promote CNS remyelination via BDNF and mTORC1 pathway 人ipsc来源的内皮细胞通过BDNF和mTORC1途径促进中枢神经系统再髓鞘形成

IF 6.2 2区医学

Glia Pub Date : 2023-09-07 DOI: 10.1002/glia.24466

Dan Ma, Huiyuan Zhang, Le Yin, Hao Xu, Lida Wu, Rahul Shaji, Fatema Rezai, Ayesha Mulla, Sukhteerath Kaur, Shengjiang Tan, Boris Kysela, Yilong Wang, Zhiguo Chen, Chao Zhao, Yuchun Gu

{"title":"Human iPSC-derived endothelial cells promote CNS remyelination via BDNF and mTORC1 pathway","authors":"Dan Ma, Huiyuan Zhang, Le Yin, Hao Xu, Lida Wu, Rahul Shaji, Fatema Rezai, Ayesha Mulla, Sukhteerath Kaur, Shengjiang Tan, Boris Kysela, Yilong Wang, Zhiguo Chen, Chao Zhao, Yuchun Gu","doi":"10.1002/glia.24466","DOIUrl":"10.1002/glia.24466","url":null,"abstract":"Damage of myelin is a component of many diseases in the central nervous system (CNS). The activation and maturation of the quiescent oligodendrocyte progenitor cells (OPCs) are the crucial cellular processes for CNS remyelination, which is influenced by neuroinflammation in the lesion microenvironment. Endothelial cells derived from human induced pluripotent stem cells (hiPSC-ECs) have shown promise in restoring function in various preclinical animal models. Here we ask whether and whether transplantation of hiPSC-ECs could benefit remyelination in a mouse model of CNS demyelination. Our results show that in vitro, hiPSC-ECs increase OPC proliferation, migration and differentiation via secreted soluble factors including brain-derived neurotrophic factor (BDNF). hiPSC-ECs also promote the survival of oligodendrocyte lineage cells in vitro and in vivo. Transplantation of hiPSC-ECs into a toxin-induced demyelination lesion in mouse corpus callosum (CC) leads to increased density of oligodendrocyte lineage cells and level of myelin in demyelinated area, correlated with a decreased neuroinflammation and an increased proportion of pro-regenerative M2 phenotype in microglia/macrophages. The hiPSC-EC-exposed oligodendrocyte lineage cells showed significant increase in the level of phosphorylated S6 ribosomal protein (pS6) both in vitro and in vivo, indicating an involvement of mTORC1 pathway. These results suggest that hiPSC-ECs may benefit myelin protection and regeneration which providing a potential source of cell therapy for a wide range of diseases and injuries associated with myelin damage.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 1","pages":"133-155"},"PeriodicalIF":6.2,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10226932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronic psychosocial stress triggers microglial-/macrophage-induced inflammatory responses leading to neuronal dysfunction and depressive-related behavior 慢性社会心理应激触发小胶质/巨噬细胞诱导的炎症反应，导致神经元功能障碍和抑郁相关行为

IF 6.2 2区医学

Glia Pub Date : 2023-09-07 DOI: 10.1002/glia.24464

Alexandros G. Kokkosis, Miguel M. Madeira, Zachary Hage, Kimonas Valais, Dimitris Koliatsis, Emran Resutov, Stella E. Tsirka

{"title":"Chronic psychosocial stress triggers microglial-/macrophage-induced inflammatory responses leading to neuronal dysfunction and depressive-related behavior","authors":"Alexandros G. Kokkosis, Miguel M. Madeira, Zachary Hage, Kimonas Valais, Dimitris Koliatsis, Emran Resutov, Stella E. Tsirka","doi":"10.1002/glia.24464","DOIUrl":"10.1002/glia.24464","url":null,"abstract":"Chronic environmental stress and traumatic social experiences induce maladaptive behavioral changes and is a risk factor for major depressive disorder (MDD) and various anxiety-related psychiatric disorders. Clinical studies and animal models of chronic stress have reported that symptom severity is correlated with innate immune responses and upregulation of neuroinflammatory cytokine signaling in brain areas implicated in mood regulation (mPFC; medial Prefrontal Cortex). Despite increasing evidence implicating impairments of neuroplasticity and synaptic signaling deficits into the pathophysiology of stress-related mental disorders, how microglia may modulate neuronal homeostasis in response to chronic stress has not been defined. Here, using the repeated social defeat stress (RSDS) mouse model we demonstrate that microglial-induced inflammatory responses are regulating neuronal plasticity associated with psychosocial stress. Specifically, we show that chronic stress induces a rapid activation and proliferation of microglia as well as macrophage infiltration in the mPFC, and these processes are spatially related to neuronal activation. Moreover, we report a significant association of microglial inflammatory responses with susceptibility or resilience to chronic stress. In addition, we find that exposure to chronic stress exacerbates phagocytosis of synaptic elements and deficits in neuronal plasticity. Importantly, by utilizing two different CSF1R inhibitors (the brain penetrant PLX5622 and the non-penetrant PLX73086) we highlight a crucial role for microglia (and secondarily macrophages) in catalyzing the pathological manifestations linked to psychosocial stress in the mPFC and the resulting behavioral deficits usually associated with depression.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 1","pages":"111-132"},"PeriodicalIF":6.2,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10173503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cover Image, Volume 71, Issue 11 封面图片，第71卷，第11期

IF 6.2 2区医学

Glia Pub Date : 2023-09-05 DOI: 10.1002/glia.24214

Tenna Bering, Camilla Gadgaard, Henrik Vorum, Bent Honoré, Martin Fredensborg Rath

引用次数: 0

Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis 神经节苷脂GD3调节神经干细胞静止并控制出生后神经发生

IF 6.2 2区医学

Glia Pub Date : 2023-09-05 DOI: 10.1002/glia.24468

Takahiro Fuchigami, Yutaka Itokazu, Robert K. Yu

{"title":"Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis","authors":"Takahiro Fuchigami, Yutaka Itokazu, Robert K. Yu","doi":"10.1002/glia.24468","DOIUrl":"10.1002/glia.24468","url":null,"abstract":"The postnatal neural stem cell (NSC) pool hosts quiescent and activated radial glia-like NSCs contributing to neurogenesis throughout adulthood. However, the underlying regulatory mechanism during the transition from quiescent NSCs to activated NSCs in the postnatal NSC niche is not fully understood. Lipid metabolism and lipid composition play important roles in regulating NSC fate determination. Biological lipid membranes define the individual cellular shape and help maintain cellular organization and are highly heterogeneous in structure and there exist diverse microdomains (also known as lipid rafts), which are enriched with sugar molecules, such as glycosphingolipids. An often overlooked but key aspect is that the functional activities of proteins and genes are highly dependent on their molecular environments. We previously reported that ganglioside GD3 is the predominant species in NSCs and that the reduced postnatal NSC pools are observed in global GD3-synthase knockout (GD3S-KO) mouse brains. The specific roles of GD3 in determining the stage and cell-lineage determination of NSCs remain unclear, since global GD3S-KO mice cannot distinguish if GD3 regulates postnatal neurogenesis or developmental impacts. Here, we show that inducible GD3 deletion in postnatal radial glia-like NSCs promotes NSC activation, resulting in the loss of the long-term maintenance of the adult NSC pools. The reduced neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of GD3S-conditional-knockout mice led to the impaired olfactory and memory functions. Thus, our results provide convincing evidence that postnatal GD3 maintains the quiescent state of radial glia-like NSCs in the adult NSC niche.","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 1","pages":"167-183"},"PeriodicalIF":6.2,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10197774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1