IF 5.4 2区医学

Glia Pub Date : 2025-03-19 DOI: 10.1002/glia.70012

Niki Ktena, Dimitrios Spyridakos, Alexandros Georgilis, Ilias Kalafatakis, Efstathia Thomoglou, Angeliki Kolaxi, Vassiliki Nikoletopoulou, Maria Savvaki, Domna Karagogeos

{"title":"Disruption of Oligodendroglial Autophagy Leads to Myelin Morphological Deficits, Neuronal Apoptosis, and Cognitive Decline in Aged Mice","authors":"Niki Ktena, Dimitrios Spyridakos, Alexandros Georgilis, Ilias Kalafatakis, Efstathia Thomoglou, Angeliki Kolaxi, Vassiliki Nikoletopoulou, Maria Savvaki, Domna Karagogeos","doi":"10.1002/glia.70012","DOIUrl":"10.1002/glia.70012","url":null,"abstract":"The aging central nervous system (CNS) is often marked by myelin degeneration, yet the underlying mechanisms remain elusive. This study delves into the previously unexplored role of autophagy in maintaining CNS myelin during aging. We generated the transgenic mouse line plpCre\u0000 \u0000 ERT2\u0000 ; atg5\u0000 \u0000 f/f\u0000 , enabling selective deletion of the core autophagic component Atg5 in oligodendrocytes (OLs) following tamoxifen administration in adulthood, while analysis was conducted on aged mice. Our findings reveal that oligodendroglial autophagy inactivation leads to significant alterations in myelin protein levels. Moreover, the ultrastructural analysis revealed pronounced myelin deficits and increased degeneration of axons, accompanied by apoptosis, as confirmed by immunohistochemistry. Behaviorally, aged knockout (cKO) mice exhibited marked deficits in learning and memory tasks, indicative of cognitive impairment. Additionally, we observed increased activation of microglia, suggesting an inflammatory response linked to the absence of autophagic activity in OLs. These results underscore the critical role of autophagy in OLs for the preservation of CNS myelin and axonal integrity during aging. Our study highlights autophagy as a vital mechanism for neural maintenance, offering potential therapeutic avenues for combating age-related neurodegenerative diseases.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 7","pages":"1383-1397"},"PeriodicalIF":5.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655899","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

Fibroblasts and hiPS-Derived Astrocytes From CoPAN Patients Showed Different Levels of Iron Overload Correlated With Senescent Phenotype 来自CoPAN患者的成纤维细胞和hips来源的星形细胞显示不同水平的铁超载与衰老表型相关。

IF 5.4 2区医学

Glia Pub Date : 2025-03-19 DOI: 10.1002/glia.70017

Anna Cozzi, Paolo Santambrogio, Andrea Stefano Moro, Alessio Pelagatti, Alicia Rubio, Chiara Balestrucci, Ivano Di Meo, Valeria Tiranti, Sonia Levi

{"title":"Fibroblasts and hiPS-Derived Astrocytes From CoPAN Patients Showed Different Levels of Iron Overload Correlated With Senescent Phenotype","authors":"Anna Cozzi, Paolo Santambrogio, Andrea Stefano Moro, Alessio Pelagatti, Alicia Rubio, Chiara Balestrucci, Ivano Di Meo, Valeria Tiranti, Sonia Levi","doi":"10.1002/glia.70017","DOIUrl":"10.1002/glia.70017","url":null,"abstract":"COASY protein-associated neurodegeneration (CoPAN) is a rare autosomal recessive disorder within the Neurodegeneration with Brain Iron Accumulation spectrum, resulting from mutations in COASY. This gene encodes the bifunctional enzyme essential for the final steps of coenzyme A biosynthesis. To elucidate the pathophysiology and iron dyshomeostasis underlying CoPAN, we analyzed fibroblasts and human induced pluripotent stem (hiPS)-derived astrocytes from two patients carrying distinct COASY mutations. Our findings reveal that CoPAN fibroblasts display altered iron homeostasis, characterized by iron aggregates, elevated cytosolic labile iron pool, and impaired tubulin acetylation. Patients hiPS-derived astrocytes showed mitochondrial morphological abnormalities and compromised vesicular trafficking. Notably, both cell types demonstrated evidence of ferroptosis, but the astrocytes exhibited more pronounced iron accumulation and lipid peroxidation. These results demonstrate that astrocytes may more accurately recapitulate the pathological phenotype of CoPAN compared to fibroblasts. Interestingly, astrocytes exhibited different levels of iron accumulation concomitant with cellular senescence, indicating a possible role of iron-induced cellular senescence. This finding suggests that the accumulation of cytosolic iron, possibly caused by mitochondrial dysfunction, actively promotes senescence. Our data emphasize the potential therapeutic efficacy of drugs that enhance mitochondrial functionality to attenuate the effects of CoPAN.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 7","pages":"1467-1482"},"PeriodicalIF":5.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655838","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

The X-Linked Intellectual Disability Gene, ZDHHC9, Is Important for Oligodendrocyte Subtype Determination and Myelination x连锁智力残疾基因ZDHHC9对少突胶质细胞亚型测定和髓鞘形成很重要

IF 5.4 2区医学

Glia Pub Date : 2025-03-19 DOI: 10.1002/glia.70016

Rocio B. White, Angela R. Wild, Timothy P. O'Leary, Andrew J. Thompson, Stephane Flibotte, Angie Peng, Jason C. Rogalski, Mila Mair, Neeki Derhami, Shernaz X. Bamji

{"title":"The X-Linked Intellectual Disability Gene, ZDHHC9, Is Important for Oligodendrocyte Subtype Determination and Myelination","authors":"Rocio B. White, Angela R. Wild, Timothy P. O'Leary, Andrew J. Thompson, Stephane Flibotte, Angie Peng, Jason C. Rogalski, Mila Mair, Neeki Derhami, Shernaz X. Bamji","doi":"10.1002/glia.70016","DOIUrl":"10.1002/glia.70016","url":null,"abstract":"Two percent of patients with X-linked intellectual disability (XLID) exhibit loss-of-function mutations in the enzyme, ZDHHC9. One of the main anatomical deficits observed in these patients is a decrease in corpus callosum volume and a concurrent disruption in white matter integrity. In this study, we demonstrate that deletion of Zdhhc9 in mice disrupts the balance of mature oligodendrocyte subtypes within the corpus callosum. While overall mature oligodendrocyte numbers are unchanged, there is a marked increase in MOL5/6 cells that are enriched in genes associated with cell adhesion and synapses, and a concomitant decrease in MOL2/3 cells that are enriched in genes associated with myelination. In line with this, we observed a decrease in the density of myelinated axons and disruptions in myelin compaction in the corpus callosum of Zdhhc9 knockout mice. RNA sequencing and proteomic analysis further revealed a reduction in genes and proteins essential for lipid metabolism, cholesterol synthesis, gene expression, and myelin compaction, offering insights into the underlying mechanisms of the pathology. These findings reveal a previously underappreciated and fundamental role for ZDHHC9 and protein palmitoylation in regulating oligodendrocyte subtype determination and myelinogenesis, offering mechanistic insights into the deficits observed in white matter volume in patients with mutations in ZDHHC9.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 7","pages":"1452-1466"},"PeriodicalIF":5.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655841","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

Cover Image, Volume 73, Issue 5 封面图片，第73卷，第5期

IF 5.4 2区医学

Glia Pub Date : 2025-03-18 DOI: 10.1002/glia.24552

Helmut Kettenmann, Bilge Ugursu, Bruce R. Ransom, Christian Steinhäuser

引用次数: 0

Cholinergic and Glutamatergic Axons Differentially Require Glial Support in the Drosophila PNS 胆碱能和谷氨酸能轴突在果蝇PNS中需要不同的胶质支持。

IF 5.4 2区医学

Glia Pub Date : 2025-03-17 DOI: 10.1002/glia.70011

Steffen Kautzmann, Simone Rey, Amber Krebs, Christian Klämbt

{"title":"Cholinergic and Glutamatergic Axons Differentially Require Glial Support in the Drosophila PNS","authors":"Steffen Kautzmann, Simone Rey, Amber Krebs, Christian Klämbt","doi":"10.1002/glia.70011","DOIUrl":"10.1002/glia.70011","url":null,"abstract":"In vertebrates, there is a differential interaction between peripheral axons and their associated glial cells. While large-caliber axons are covered by a myelin sheath, small-diameter axons are simply wrapped in Remak fibers. In peripheral nerves of Drosophila larvae, axons are covered by wrapping glial cell processes similar to vertebrate Remak fibers. Whether differences in axonal diameter influence the interaction with glial processes in Drosophila has not yet been analyzed. Likewise, it is not understood whether the modality of the neuron affects the interaction with the wrapping glia. To start to decipher the mechanisms underlying glial wrapping, we employed APEX2 labeling in larval filet preparations. This allowed us to follow individual axons of defined segmental nerves at ultrastructural resolution in the presence or absence of wrapping glia. Using these tools, we first demonstrate that motor axons are larger compared to sensory axons. Sensory axons fasciculate in larger groups than motor axons, suggesting that they do not require direct contact with wrapping glia. However, unlike motor axons, sensory axons show length-dependent degeneration upon ablation of wrapping glia. These data suggest that Drosophila may help to understand peripheral neuropathies caused by defects in Schwann cell function, in which a similar degeneration of sensory axons is observed.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 7","pages":"1365-1382"},"PeriodicalIF":5.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646567","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

Amyloid-β Dysregulates Oligodendroglial Lineage Cell Dynamics and Myelination via PKC in the Zebrafish Spinal Cord 淀粉样蛋白-β通过PKC调控斑马鱼脊髓少突胶质谱系细胞动力学和髓鞘形成。

IF 5.4 2区医学

Glia Pub Date : 2025-03-14 DOI: 10.1002/glia.70015

Uxue Balantzategi, Adhara Gaminde-Blasco, Christina A. Kearns, Laura Bayón-Cordero, María Victoria Sánchez-Gómez, José Luis Zugaza, Bruce Appel, Elena Alberdi

{"title":"Amyloid-β Dysregulates Oligodendroglial Lineage Cell Dynamics and Myelination via PKC in the Zebrafish Spinal Cord","authors":"Uxue Balantzategi, Adhara Gaminde-Blasco, Christina A. Kearns, Laura Bayón-Cordero, María Victoria Sánchez-Gómez, José Luis Zugaza, Bruce Appel, Elena Alberdi","doi":"10.1002/glia.70015","DOIUrl":"10.1002/glia.70015","url":null,"abstract":"Soluble forms of amyloid-β (Aβ) peptide have been proposed as candidates to induce oligodendrocyte (OL) and myelin dysfunctions in the early stages of Alzheimer's disease (AD) pathology. Nevertheless, little is known about how Aβ affects OL differentiation and myelination in vivo, and the underlying molecular mechanisms. In this study, we explored the effects of a brain intraventricular injection of Aβ on OLs and myelin in the developing spinal cord of zebrafish larvae. Using quantitative fluorescent in situ RNA hybridization assays, we demonstrated that Aβ altered myrf and mbp mRNA levels and the regional distribution of mbp during larval development, suggesting an early differentiation of OLs. Through live imaging of Tg(myrf:mScarlet) and Tg(mbpa:tagRFP) zebrafish lines, both crossed with Tg(olig2:EGFP), we found that Aβ increased the number of myrf\u0000 + and mbp\u0000 + OLs in the dorsal spinal cord at 72 hpf and 5 dpf, respectively, without affecting total cell numbers. Furthermore, Aβ also increased the number of Sox10+cells, myelin sheaths per OL, and the number of myelinated axons in the dorsal spinal cord at 8 dpf compared to vehicle-injected control animals. Interestingly, the treatment of Aβ-injected zebrafish with the pan-PKC inhibitor Gö6983 restored the aforementioned alterations in OLs and myelin to control levels. Altogether, not only do we demonstrate that Aβ induces a precocious oligodendroglial differentiation leading to dysregulated myelination, but we also identified PKC as a key player in Aβ-induced pathology.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 7","pages":"1437-1451"},"PeriodicalIF":5.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633281","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

Temporal Profiling of Male Cortical Astrocyte Transcription Predicts Molecular Shifts From Early Development to Aging 男性皮质星形胶质细胞转录的时间谱预测从早期发育到衰老的分子转变。

IF 5.4 2区医学

Glia Pub Date : 2025-03-13 DOI: 10.1002/glia.70010

Xiaoran Wei, Jiangtao Li, Michelle L. Olsen

{"title":"Temporal Profiling of Male Cortical Astrocyte Transcription Predicts Molecular Shifts From Early Development to Aging","authors":"Xiaoran Wei, Jiangtao Li, Michelle L. Olsen","doi":"10.1002/glia.70010","DOIUrl":"10.1002/glia.70010","url":null,"abstract":"Astrocytes are the most abundant glial cell type in the central nervous system (CNS). Astrocytes are born during the early postnatal period in the rodent brain and mature alongside neurons, demonstrating remarkable morphological structural complexity, which is attained in the second postnatal month. Throughout this period of development and across the remainder of the lifespan, astrocytes participate in CNS homeostasis, support neuronal partners, and contribute to nearly all aspects of CNS function. In the present study, we analyzed astrocyte gene expression in the cortex of wild-type male rodents throughout their lifespan (postnatal 7 days to 18 months). A pairwise timepoint comparison of differential gene expression during early development and CNS maturation (7–60 days) revealed four unique astrocyte gene clusters, each with hundreds of genes, which demonstrate unique temporal profiles. These clusters are distinctively related to cell division, cell morphology, cellular communication, and vascular structure and regulation. A similar analysis across adulthood and in the aging brain (3 to 18 months) identified similar patterns of grouped gene expression related to cell metabolism and cell structure. Additionally, our analysis identified that during the aging process astrocytes demonstrate a bias toward shorter transcripts, with loss of longer genes related to synapse development and a significant increase in shorter transcripts related to immune regulation and the response to DNA damage. Our study highlights the critical role that astrocytes play in maintaining CNS function throughout life and reveals molecular shifts that occur during development and aging in the cortex of male mice.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 7","pages":"1349-1364"},"PeriodicalIF":5.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613044","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

Unexpected Remyelination in the Absence of Matrix Metalloproteinase 7 缺乏基质金属蛋白酶的意外再髓鞘形成

IF 5.4 2区医学

Glia Pub Date : 2025-03-10 DOI: 10.1002/glia.70005

Rianne P. Gorter, Andrea J. Arreguin, Wendy Oost, Jenny C. de Jonge, Harm H. Kampinga, Sandra Amor, Holly Colognato, Wia Baron

{"title":"Unexpected Remyelination in the Absence of Matrix Metalloproteinase 7","authors":"Rianne P. Gorter, Andrea J. Arreguin, Wendy Oost, Jenny C. de Jonge, Harm H. Kampinga, Sandra Amor, Holly Colognato, Wia Baron","doi":"10.1002/glia.70005","DOIUrl":"10.1002/glia.70005","url":null,"abstract":"In multiple sclerosis (MS), an influx of immune cells into the central nervous system leads to focal demyelinating lesions in the brain, optic nerve, and spinal cord. As MS progresses, remyelination increasingly fails, leaving neuronal axons vulnerable to degeneration and resulting in permanent neurological disability. In chronic MS lesions, the aberrant accumulation of extracellular matrix (ECM) molecules, including fibronectin and hyaluronan, impairs oligodendrocyte progenitor cell differentiation, contributing to remyelination failure. Removing inhibitory ECM is therefore a therapeutic target to stimulate remyelination in MS. Intriguingly, the expression of the fibronectin-degrading enzyme matrix metalloproteinase 7 (MMP7) is decreased in chronic MS lesions compared to control white matter. Therefore, we examined the role of MMP7 upon cuprizone-induced demyelination, hypothesizing that the lack of MMP7 would lead to impaired breakdown of its ECM substrates, including fibronectin, and diminished remyelination. Unexpectedly, remyelination proceeded efficiently in the absence of MMP7. In the remyelination phase, the lack of MMP7 did not lead to the accumulation of fibronectin or of laminin, another MMP7 substrate. Moreover, in the setting of chronic demyelination, levels of fibronectin were actually lower in MMP7−/− mice, while levels of hyaluronan, which is not a known MMP7 substrate, were also lower. Overall, these results indicate that MMP7 is not essential for remyelination in the cuprizone model and point to an unexpected complexity in how MMP7 deficiency influences fibronectin and hyaluronan levels in chronic demyelination.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 6","pages":"1288-1306"},"PeriodicalIF":5.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583880","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

Neuroinflammation: An Oligodendrocentric View 神经炎症：少突中心的观点。

IF 5.4 2区医学

Glia Pub Date : 2025-03-10 DOI: 10.1002/glia.70007

Lindsay K. Festa, Kelly L. Jordan-Sciutto, Judith B. Grinspan

{"title":"Neuroinflammation: An Oligodendrocentric View","authors":"Lindsay K. Festa, Kelly L. Jordan-Sciutto, Judith B. Grinspan","doi":"10.1002/glia.70007","DOIUrl":"10.1002/glia.70007","url":null,"abstract":"<div>\u0000 \u0000 Chronic neuroinflammation, driven by central nervous system (CNS)-resident astrocytes and microglia, as well as infiltration of the peripheral immune system, is an important pathologic mechanism across a range of neurologic diseases. For decades, research focused almost exclusively on how neuroinflammation impacted neuronal function; however, there is accumulating evidence that injury to the oligodendrocyte lineage is an important component for both pathologic and clinical outcomes. While oligodendrocytes are able to undergo an endogenous repair process known as remyelination, this process becomes inefficient and usually fails in the presence of sustained inflammation. The present review focuses on our current knowledge regarding activation of the innate and adaptive immune systems in the chronic demyelinating disease, multiple sclerosis, and provides evidence that sustained neuroinflammation in other neurologic conditions, such as perinatal white matter injury, traumatic brain injury, and viral infections, converges on oligodendrocyte injury. Lastly, the therapeutic potential of targeting the impact of inflammation on the oligodendrocyte lineage in these diseases is discussed.\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 6","pages":"1113-1129"},"PeriodicalIF":5.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583877","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

The INO80 Chromatin Remodeling Complex Regulates Histone H2A.Z Mobility and the G1-S Transition in Oligodendrocyte Precursors INO80染色质重塑复合体调控组蛋白H2A。少突胶质细胞前体的Z迁移率和G1-S转变。

IF 5.4 2区医学

Glia Pub Date : 2025-02-28 DOI: 10.1002/glia.70006

Jordan L. Wright, Yi Jiang, Stuart G. Nayar, Huiliang Li, William D. Richardson

{"title":"The INO80 Chromatin Remodeling Complex Regulates Histone H2A.Z Mobility and the G1-S Transition in Oligodendrocyte Precursors","authors":"Jordan L. Wright, Yi Jiang, Stuart G. Nayar, Huiliang Li, William D. Richardson","doi":"10.1002/glia.70006","DOIUrl":"10.1002/glia.70006","url":null,"abstract":"Chromatin remodeling complexes (CRCs) participate in oligodendrocyte (OL) differentiation, survival, and maintenance. We asked whether CRCs also control the proliferation of OL precursors (OPs)—focusing on the INO80 complex, which is known to regulate the proliferation of a variety of other cell types during development and disease. CRISPR/Cas9-mediated inactivation of Ino80 in vitro, or Cre-mediated deletion in vivo, slowed the OP cell cycle substantially by prolonging G1. RNAseq analysis revealed that E2F target genes were dysregulated in OPs from INO80-deficient mice, but correlated RNAseq and ATAC-seq uncovered no general correlation between gene expression and altered nucleosome positioning at transcription start sites. Fluorescence photobleaching experiments in cultured OPs demonstrated that histone H2A.Z mobility increased following the loss of INO80, suggesting that INO80 regulates the cell cycle machinery in OPs through H2A.Z/H2A exchange. We also present evidence that INO80 associates with OLIG2, a master regulator of OL development.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 6","pages":"1307-1323"},"PeriodicalIF":5.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522290","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

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