Cell and Bioscience最新文献

{"title":"The RBM39 degrader indisulam inhibits acute megakaryoblastic leukemia by altering the alternative splicing of ZMYND8.","authors":"Ying Yang, Zhiheng Li, Yang Yang, Peifang Xiao, Zhixu He, Zimu Zhang, Yizhen Li, Lei Shi, Xiaodong Wang, Yanfang Tao, Junjie Fan, Fenli Zhang, Chunxia Yang, Fahua Yao, Tongting Ji, Yongping Zhang, Bi Zhou, Juanjuan Yu, Ailian Guo, Zhongling Wei, Wanyan Jiao, Yumeng Wu, Yan Li, Di Wu, Yijun Wu, Li Gao, Yixin Hu, Jian Pan, Shaoyan Hu, Xiaoyan Yang","doi":"10.1186/s13578-025-01380-3","DOIUrl":"https://doi.org/10.1186/s13578-025-01380-3","url":null,"abstract":"<p><strong>Background: </strong>Acute megakaryoblastic leukemia (AMKL) is a rare hematological malignancy in adults but children. Alternative splicing (AS) has been shown to affect hematological cancer progression, making splicing factors promising targets. Our research aims to investigate the efficacy of the molecular glue degrader indisulam, which targets the splicing factor RNA binding motif protein 39 (RBM39) in AMKL models.</p><p><strong>Results: </strong>Public drug sensitivity data analysis revealed that AMKL cell lines exhibited the highest sensitivity to indisulam compared with other tumor types. Then we confirmed that RBM39 depletion by indisulam treatment induced AMKL cell cycle arrest and apoptosis. In AMKL mouse model, indisulam treatment significantly reduced the leukemic burden and prolonged the lifetime of AMKL mice. Mechanically, integration of transcriptomic and proteomic analyses revealed that indisulam-mediated RBM39 degradation resulted in AS of the transcription factor zinc finger MYND-type containing 8 (ZMYND8), an AMKL cell growth regulator. Finally, the effectiveness of indisulam depended on DDB1- and Cul4- Associated Factor 15 (DCAF15) expression because knockout of DCAF15 rescued the indisulam-induced RBM39 degradation and mis-splicing of ZMYND8.</p><p><strong>Conclusion: </strong>Indisulam is a promising therapeutic candidate for AMKL and the RBM39-mediated ZMYND8 splicing plays an important role in promoting the development of AMKL.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"46"},"PeriodicalIF":6.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated ac4C modification of mRNA in a mouse model of early-stage Alzheimer's disease.","authors":"Hao-Nan Ji, Hai-Qian Zhou, Jing-Bo Qie, Wen-Mei Lu, Hai-Tao Gao, Dan-Hong Wu","doi":"10.1186/s13578-025-01389-8","DOIUrl":"https://doi.org/10.1186/s13578-025-01389-8","url":null,"abstract":"<p><strong>Background: </strong>The identification and intervention of Alzheimer's Disease (AD) in its early-stage allows for the timely implementation of lifestyle modifications and therapeutic strategies. Although dysregulation of protein expression has been reported in the brain from AD patients and AD animal models, the underlying mechanisms remain poorly understood. N4-acetylcytidine (ac4C), the only known form of RNA acetylation in eukaryotes, has recently been shown to regulate mRNA stability and translation efficiency. However, the dysregulation of ac4C associated with abnormal protein expression levels in the brain of early-stage mouse models of AD remains to be elucidated.</p><p><strong>Methods: </strong>This study investigated ac4C modifications, mRNA and protein expression in the hippocampus of 3 and 6-month-old 5×FAD mice, a mouse model of AD, and wild-type (WT) littermates. The multi-omics analysis was performed: acetylated RNA immunoprecipitation followed by next-generation sequencing (acRIP-seq) to identify ac4C mRNAs, deep RNA sequencing (RNA-seq) to quantify mRNA abundance, and label-free quantitative proteomics to assess protein expression levels. In addition, we used acRIP-qPCR, regular qPCR and western blots to verify the ac4C, mRNA and protein levels of some key genes that were identified by the high-throughput assays.</p><p><strong>Results: </strong>Proteomic analysis revealed significant change of protein expression in the hippocampus of 3-months-old 5×FAD mice, compared with WT littermates. In contrast, RNA-seq analysis indicated that there were no substantial alterations in mRNA expression levels in the hippocampus of 3-months-old 5×FAD mice, compared to WT littermates. Strikingly, acRIP-seq revealed notable variations in ac4C modification on mRNAs, particularly those associated with synaptic structure and function, in the hippocampus of 3-months-old 5×FAD mice, compared with WT littermates. The ac4C modifications were found to be correlated with protein expression changes. Genes that are essential for synaptic function and cognition, including GRIN1, MAP2, and DNAJC6, exhibited reduced ac4C and protein levels in 3-months-old 5×FAD mice, without any corresponding changes in the mRNA levels, compared with WT littermates. Moreover, only a small part of dysregulated ac4C mRNAs identified in the 3-month-old 5×FAD mice were found in the 6-month-old 5×FAD mice.</p><p><strong>Conclusions: </strong>Altogether these results identified abnormal ac4C modification of mRNAs that may contribute to the dysregulation of protein synthesis in the hippocampus from an early-stage mouse model of AD.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"45"},"PeriodicalIF":6.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special correlation between diet and MASLD: positive or negative?","authors":"Jia Liu, Changmeng Li, Yun Yang, Jingtao Li, Xiaoguang Sun, Yinqiang Zhang, Runping Liu, Fafeng Chen, Xiaojiaoyang Li","doi":"10.1186/s13578-025-01382-1","DOIUrl":"https://doi.org/10.1186/s13578-025-01382-1","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic and systemic metabolic liver disease characterized by the presence of hepatic steatosis and at least one cardiometabolic risk factor (CMRF). The pathogenesis of MASLD involves multiple mechanisms, including lipid metabolism disorders, insulin resistance, inflammatory responses, and the hepato-intestinal axis of metabolic dysfunction. Among these factors, diet serves as both an inducement and a potential remedy in the disease's development. Notably, a high-lipid diet exacerbates fat accumulation, oxidative stress, and inflammatory responses, thereby promoting the progression of MASLD. Consequently, dietary induction models have become vital tools for studying the pathological mechanisms of MASLD, providing a foundation for identifying potential therapeutic targets. Additionally, we summarize the therapeutic effects of dietary optimization on MASLD and elucidate the role of specific dietary components in regulating the hepato-intestinal axis, lipid metabolism, and inhibiting inflammatory responses. In conclusion, studies utilizing animal models of MASLD offer significant insights into dietary therapy, particularly concerning the regulation of lipid metabolism-related and hepatoenteric axis-related signaling pathways as well as the beneficial mechanism of probiotics in hepatoenteric regulation. By understanding the specific mechanisms by which different dietary patterns affect MASLD, we can assess the clinical applicability of current dietary strategies and provide new directions for research and treatment aimed at disease modification.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"44"},"PeriodicalIF":6.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of SARS-CoV-2 spike protein exposure on retinal development in the human retinal organoids.","authors":"Jing Gong, Lingling Ge, Yuxiao Zeng, Cao Yang, Yushan Luo, Jiahui Kang, Ting Zou, Haiwei Xu","doi":"10.1186/s13578-025-01383-0","DOIUrl":"https://doi.org/10.1186/s13578-025-01383-0","url":null,"abstract":"<p><strong>Background: </strong>Pregnant women are considered a high-risk population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as the virus can infect the placenta and embryos. Recently, SARS-CoV-2 has been widely reported to cause retinal pathological changes and to infect the embryonic retina. The infection of host cells by SARS-CoV-2 is primarily mediated through spike (S) protein, which also plays a crucial role in the pathogenesis of SARS-CoV-2. However, it remains poorly understood how the S protein of SARS-CoV-2 affects retinal development, and the underlying mechanism has not yet been clarified.</p><p><strong>Methods: </strong>We used human embryonic stem cell-derived retinal organoids (hEROs) as a model to study the effect of S protein exposure at different stages of retinal development. hEROs were treated with 2 μg/mL of S protein on days 90 and 280. Immunofluorescence staining, RNA sequencing, and RT-PCR were performed to assess the influence of S protein exposure on retinal development at both early and late stages.</p><p><strong>Results: </strong>The results showed that ACE2 and TMPRSS2, the receptors facilitating SARS-CoV-2 entry into host cells, were expressed in hEROs. Exposure to the S protein induced an inflammatory response in both the early and late stages of retinal development in the hEROs. Additionally, RNA sequencing indicated that early exposure of the S protein to hEROs affected nuclear components and lipid metabolism, while late-stages exposure resulted in changes to cell membrane components and the extracellular matrix.</p><p><strong>Conclusion: </strong>This work highlights the differential effects of SARS-CoV-2 S protein exposure on retinal development at both early and late stages, providing insights into the cellular and molecular mechanisms underlying SARS-CoV-2-induced developmental impairments in the human retina.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"43"},"PeriodicalIF":6.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11987193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared and distinct peripheral blood immune cell landscape in MCTD, SLE, and pSS.","authors":"Yanling Cui, Huina Zhang, Yaxuan Deng, Orion Fan, Junbang Wang, Zhonggang Xing, Jianping Tang, Wenmin Zhu, Bangdong Gong, Yi Eve Sun","doi":"10.1186/s13578-025-01374-1","DOIUrl":"https://doi.org/10.1186/s13578-025-01374-1","url":null,"abstract":"<p><strong>Background: </strong>Mixed connective tissue disease (MCTD) is a rare autoimmune disease, and little is known about its pathogenesis. Furthermore, MCTD, systemic lupus erythematosus (SLE), and primary Sjögren's syndrome (pSS) share many clinical, laboratory, and immunological manifestations. This overlap complicates early diagnosis and accurate treatment.</p><p><strong>Methods: </strong>The transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) from MCTD patients was performed using both bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) for the first time. Additionally, we applied MCTD scRNA-seq data, along with datasets from SLE (GSE135779) and pSS (GSE157278) from the Gene Expression Omnibus database, to characterize and compare the similarities and heterogeneity among MCTD, SLE, and pSS.</p><p><strong>Results: </strong>We first resolved transcriptomic changes in peripheral blood immune cells of MCTD, and then revealed the shared and unique features among MCTD, SLE, and pSS. Analyses showed that the percentage of CD8⁺ effector T cells was increased, while mucosal-associated invariant T cells were decreased in all three diseases. Genes related to the 'interferon (IFN) γ response' and 'IFN α response' were significantly upregulated. SCENIC analysis revealed activation of STAT1 and IRF7 in disease states, targeting IFN-related genes. The IFN-II signaling network was notably elevated in all three diseases. Unique features of MCTD, SLE, and pSS were also identified.</p><p><strong>Conclusion: </strong>We dissected the immune landscape of MCTD at single-cell resolution, providing new insights into the development of novel biomarkers and immunotherapies for MCTD. Furthermore, we offer insights into the transcriptomic similarities and heterogeneity across different autoimmune diseases, while highlighting prospective therapeutic targets.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"42"},"PeriodicalIF":6.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of the 661W cell line as a tool to facilitate treatment development for retinal diseases.","authors":"Alicia A Brunet, Rebekah E James, Petria Swanson, Livia S Carvalho","doi":"10.1186/s13578-025-01381-2","DOIUrl":"10.1186/s13578-025-01381-2","url":null,"abstract":"<p><p>Retinal diseases encompass a diverse group of disorders that affect the structure and function of the retina, leading to visual impairment and, in some cases, irreversible vision loss. The investigation of retinal diseases is crucial for understanding their underlying mechanisms, identifying potential therapeutic targets, and developing effective treatments. The use of in vitro cell models has become instrumental in advancing our knowledge of these disorders, but given that these conditions usually affect retinal neuronal cell types, access to appropriate cell models can be potentially challenging. Among the available in vitro cell models, the 661W cone-like cell line has emerged as a valuable tool for studying various retinal diseases, ranging from monogenic conditions, such as inherited retinal diseases, to complex conditions such as age-related macular degeneration (AMD), diabetic retinopathy, amongst others. Developed from immortalized murine photoreceptor cells, and freely available for academics from its creator, the 661W cell line has offered visual scientists and clinicians around the world a reliable and well-characterised platform for investigating disease pathogenesis, exploring disease-specific molecular signatures, and evaluating potential therapeutic interventions. This review aims to provide an overview of the 661W cell line and its applications in the study of both inherited and acquired retinal diseases. By examining the applications and limitations of this unique cell line, we may gain valuable insights into its contributions in unravelling the complexities of retinal diseases and its potential impact on the development of novel treatments for these diseases.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"41"},"PeriodicalIF":6.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of OBSCN expression promotes bladder cancer progression but enhances the efficacy of PD-L1 inhibitors.","authors":"Tao Wang, Tuanjie Guo, Juanjuan Sun, Xinyue Zang, Lei Dong, Jian Zhang, Siteng Chen, Guihua Chen, Sicong Ma, Xinyu Zhai, Chuanmin Chu, Chaofu Wang, Xiang Wang, Dongliang Xu, Mingyue Tan","doi":"10.1186/s13578-025-01379-w","DOIUrl":"10.1186/s13578-025-01379-w","url":null,"abstract":"<p><strong>Background: </strong>As the objective overall response rate to immune checkpoint inhibitors (ICIs) is less than 30% in late stage or metastatic bladder cancer (BLCA), elucidating the intrinsic mechanisms of immune evasion is of great importance for the discovery of predictive and prognostic biomarkers and the exploration of novel targets for intervention. Recent studies have shown that OBSCN and the cytoskeletal protein it encodes, obscurin, play an important role in tumour progression. However, no studies have reported the role of OBSCN in BLCA.</p><p><strong>Methods: </strong>RNA sequencing and clinical data were downloaded from multiple public databases including The Cancer Genome Atlas and the Gene Expression Omnibus. Immunohistochemistry (IHC) was performed on tissue microarrays including 80 BLCA patients from Shuguang Hospital. Kaplan-Meier curves with log-rank test, univariate and multivariate COX regression were performed to evaluate the prognostic efficacy of OBSCN expression. In vitro experiments were conducted to determine the role of OBSCN deficiency in promoting BLCA progression. Pan-cancer tumour immune microenvironment (TIME) analysis was performed to explore the potential correlation between OBSCN deficiency and immune evasion.</p><p><strong>Results: </strong>Pan-cancers and single-cell sequencing analysis revealed that the expression level and proportion of OBSCN was significantly decreased in BLCA cells compared to normal urothelium. Survival curves showed that BLCA patients with low OBSCN expression had a worse prognosis, yet a better clinical response to PD-L1 ICIs. Gene set variation analysis and Gene set enrichment analysis revealed that epithelial-mesenchymal transition (EMT) and immune-related processes were significantly enriched in BLCA samples with low OBSCN expression. In vitro experiments identified that OBSCN-deficient BLCA cells enhanced invasion, migration and EMT. Pan-cancer analysis of TIME revealed that neoantigen, tumor mutation burden, CD8⁺T cells and immune checkpoints were significantly negatively associated with OBSCN expression. IHC and Western blot assay identified that BLCA samples with low OBSCN expression had more CD8⁺ T-cell infiltration and higher PD-L1 expression.</p><p><strong>Conclusions: </strong>This study confirmed that BLCA patients with low OBSCN expression had a worse prognosis but a superior response to ICIs, providing a reference for individualised treatment of BLCA patients.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"40"},"PeriodicalIF":6.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural basis of human ABCC4 recognition of cAMP and ligand recognition flexibility.","authors":"Xuepeng Wen, Kaixue Si, Dantong Zhu, Anqi Zhang, Changyou Guo, Minghui Li, Weiming Tian","doi":"10.1186/s13578-025-01377-y","DOIUrl":"10.1186/s13578-025-01377-y","url":null,"abstract":"<p><strong>Background: </strong>ABCC4 (ATP-binding cassette sub-family C member 4) is a transporter protein that is primarily localized to the plasma membrane, and its efflux activity is associated with the progression of various cancers and the development of drug resistance. Cyclic adenosine monophosphate (cAMP) is an important biomolecule that is considered a transport substrate of ABCC4. However, there is currently no direct structural understanding of how ABCC4 binds cAMP, and the mechanisms by which it recognizes a diverse range of substrate ligands remain poorly understood. Some studies have indicated that, under physiological conditions, cAMP does not significantly stimulate the ATPase activity of ABCC4, making the commonly used ATPase activity assays for ABC proteins unsuitable for studying cAMP.</p><p><strong>Results: </strong>Here, we successfully resolved the cryo-electron microscopy (cryo-EM) structure of the human ABCC4-cAMP (hABCC4-cAMP) complex, revealing how hABCC4 binds to cAMP and identifying the key residues involved. This structure was compared with two other hABCC4 complex structures we obtained (Methotrexate and Prostaglandin E₂) and with previously published structures. We discovered some new structural insights into how hABCC4 binds ligands. On the basis of the structural information obtained, we confirmed the feasibility of using 8-[Fluo]-cAMP in a transport assay to detect cAMP translocation and found that some challenges remain to be addressed.</p><p><strong>Conclusions: </strong>These results suggest that hABCC4 can bind cAMP and exhibits varying degrees of flexibility when binding with different substrates, including cAMP. These findings expand our understanding of the structural biology of ABCC4.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"39"},"PeriodicalIF":6.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal CD47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild-type and Alzheimer's mouse models.","authors":"Wenjie Hu, Mengting Chen, Yuxue Lin, Hui Zhang, Li Sun, Wei Shao, Yuping Ye, Yujie Cheng, Shanshan Zhou, Panpan Hu, Xingqi Wu, Yin Xu, Kai Wang","doi":"10.1186/s13578-025-01378-x","DOIUrl":"10.1186/s13578-025-01378-x","url":null,"abstract":"<p><strong>Background: </strong>Microglia are brain-resident macrophages that play a crucial role in synapse pruning during the development and progression of various neuropsychiatric disorders, including autism spectrum disorder (ASD) and Alzheimer's disease (AD). Mechanistically, CD47 protein acts as a potent 'do not eat me' signal, protecting synapses from phagocytosis by microglia. However, the functional role of the upregulated neuronal CD47 signal under both physiological and pathological conditions remains unclear.</p><p><strong>Results: </strong>We utilized an adeno-associated virus gene expression system to induce neuron-specific overexpression of CD47 in wild-type and 5xFAD mice, assessing its effects on microglial synaptic phagocytosis and mouse behaviors. Our results indicate that neuronal CD47 induces ASD-like behaviors and synaptic pruning defects, while promoting behavioral disinhibition and improving memory in wild-type mice. Single-nucleus RNA sequencing was employed to profile gene expression patterns in subpopulations of neurons and microglia. Notably, neuronal CD47 enhances synaptic pathways in neurons and particularly shifts microglial subpopulations from a disease-associated state to a homeostatic state. Additionally, neuronal CD47 reduces excessive microglial synaptic phagocytosis induced by Aβ pathology in 5xFAD mice.</p><p><strong>Conclusion: </strong>Our study provides evidence that neuronal CD47 overexpression results in synaptic pruning defects and is involved in the pathogenesis of ASD, while also playing a beneficial role in mitigating excessive synaptic loss in Alzheimer's disease.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"38"},"PeriodicalIF":6.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: L-Arginine, as an essential amino acid, is a potential substitute for treating COPD via regulation of ROS/NLRP3/NF-κB signaling pathway.","authors":"Chunhua Ma, Kexi Liao, Jing Wang, Tao Li, Liangming Liu","doi":"10.1186/s13578-025-01373-2","DOIUrl":"10.1186/s13578-025-01373-2","url":null,"abstract":"","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"37"},"PeriodicalIF":6.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}