Cell insight最新文献_第9页

ULI-ssDRIP-seq revealed R-loop dynamics during vertebrate early embryogenesis ULI-ssDRIP-seq揭示脊椎动物早期胚胎发生过程中的R环动态变化

Cell insight Pub Date : 2024-08-01 Epub Date: 2024-06-01 DOI: 10.1016/j.cellin.2024.100179

Wei Xu , Xin Liu , Jinjin Li , Changbin Sun , Luxi Chen , Jincong Zhou , Kuan Li , Qin Li , Anming Meng , Qianwen Sun

{"title":"ULI-ssDRIP-seq revealed R-loop dynamics during vertebrate early embryogenesis","authors":"Wei Xu , Xin Liu , Jinjin Li , Changbin Sun , Luxi Chen , Jincong Zhou , Kuan Li , Qin Li , Anming Meng , Qianwen Sun","doi":"10.1016/j.cellin.2024.100179","DOIUrl":"10.1016/j.cellin.2024.100179","url":null,"abstract":"<div><p>R-loop, a chromatin structure containing one RNA:DNA hybrid and one unpaired single-stranded DNA, plays multiple biological roles. However, due to technical limitations, the landscapes and potential functions of R-loops during embryogenesis remain elusive. Here, we developed a quantitative and high-resolution ultra-low input R-loop profiling method, named ULI-ssDRIP-seq, which can map global R-loops with as few as 1000 cells. By using ULI-ssDRIP-seq, we reveal the R-loop dynamics in the zebrafish from gametes to early embryos. In oocytes, the R-loop level is relatively low in most regions of the nuclear genome, except maternal-inherited rDNA and mitochondrial genome. The correlation between R-loop and CG methylation dynamics during early development is relatively weak. Furthermore, either up- or down-regulation of global R-loops by knockdown or overexpression of RNase H1 causes a delay of embryonic development with dramatic expression changes in zygotic and maternal genes. This study provides comprehensive R-loop landscapes during early vertebrate embryogenesis and demonstrates the implication of R-loops in embryonic development.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 4","pages":"Article 100179"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000348/pdfft?md5=845ed7a5b7e0179ac90c1b9e6fcac5a7&pid=1-s2.0-S2772892724000348-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141281137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optimizing antigen selection for the development of tuberculosis vaccines 优化抗原选择以开发结核病疫苗

Cell insight Pub Date : 2024-06-01 Epub Date: 2024-03-16 DOI: 10.1016/j.cellin.2024.100163

Yang Yang , Yi-Zhen Chen , Tian Xia

{"title":"Optimizing antigen selection for the development of tuberculosis vaccines","authors":"Yang Yang , Yi-Zhen Chen , Tian Xia","doi":"10.1016/j.cellin.2024.100163","DOIUrl":"10.1016/j.cellin.2024.100163","url":null,"abstract":"<div><p>Tuberculosis (TB) remains a prevalent global infectious disease caused by genetically closely related tubercle bacilli in <em>Mycobacterium tuberculosis</em> complex (MTBC). For a century, the Bacillus Calmette-Guérin (BCG) vaccine has been the primary preventive measure against TB. While it effectively protects against extrapulmonary forms of pediatric TB, it lacks consistent efficacy in providing protection against pulmonary TB in adults. Consequently, the exploration and development of novel TB vaccines, capable of providing broad protection to populations, have consistently constituted a prominent area of interest in medical research. This article presents a concise overview of the novel TB vaccines currently undergoing clinical trials, discussing their classification, protective efficacy, immunogenicity, advantages, and limitations. In vaccine development, the careful selection of antigens that can induce strong and diverse specific immune responses is essential. Therefore, we have summarized the molecular characteristics, biological function, immunogenicity, and relevant studies associated with the chosen antigens for TB vaccines. These insights gained from vaccines and immunogenic proteins will inform the development of novel mycobacterial vaccines, particularly mRNA vaccines, for effective TB control.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 3","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277289272400018X/pdfft?md5=28d7d06a013d7480bbc9a9a9167eed03&pid=1-s2.0-S277289272400018X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140271468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 development and the genetic diseases of the ciliary body 睫状体的发育和遗传疾病

Cell insight Pub Date : 2024-06-01 Epub Date: 2024-03-15 DOI: 10.1016/j.cellin.2024.100162

Baige Li , Ting Xie , Scott Nawy , Yin Shen

引用次数: 0

Role of tumor cell pyroptosis in anti-tumor immunotherapy 肿瘤细胞热解在抗肿瘤免疫疗法中的作用

Cell insight Pub Date : 2024-06-01 Epub Date: 2024-02-10 DOI: 10.1016/j.cellin.2024.100153

Lincheng Zhang , Haotian Bai , Jing Zhou , Lilin Ye , Leiqiong Gao

{"title":"Role of tumor cell pyroptosis in anti-tumor immunotherapy","authors":"Lincheng Zhang , Haotian Bai , Jing Zhou , Lilin Ye , Leiqiong Gao","doi":"10.1016/j.cellin.2024.100153","DOIUrl":"10.1016/j.cellin.2024.100153","url":null,"abstract":"<div><p>Peripheral tumor-specific CD8<sup>+</sup> T cells often fail to infiltrate into tumor parenchyma due to the immunosuppression of tumor microenvironment (TME). Meanwhile, a significant portion of tumor-specific CD8<sup>+</sup> T cells infiltrated into TME are functionally exhausted. Despite the enormous success of anti-PD-1/PD-L1 immune-checkpoint blockade (ICB) treatment in a wide variety of cancer types, the majority of patients do not respond to this treatment largely due to the failure to efficiently drive tumor-specific CD8<sup>+</sup> T cell infiltration and reverse their exhaustion states. Nowadays, tumor cell pyroptosis, a unique cell death executed by pore-forming gasdermin (GSDM) family proteins dependent or independent on inflammatory caspase activation, has been shown to robustly promote immune-killing of tumor cells by enhancing tumor immunogenicity and altering the inflammatory state in the TME, which would be beneficial in overcoming the shortages of anti-PD-1/PD-L1 ICB therapy. Therefore, in this review we summarize the current progresses of tumor cell pyroptosis in enhancing immune function and modulating TME, which synergizes anti-PD-1/PD-L1 ICB treatment to achieve better anti-tumor effect. We also enumerate several strategies to better amply the efficiency of anti-PD-1/PD-L1 ICB therapy by inducing tumor cell pyroptosis.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 3","pages":"Article 100153"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000087/pdfft?md5=39a7d9101fba716296014a6bd04f729f&pid=1-s2.0-S2772892724000087-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139872599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cortactin-dependent control of Par1b-regulated epithelial cell polarity in Helicobacter infection 在螺旋杆菌感染过程中，Par1b调控的上皮细胞极性受Cortactin依赖性控制

Cell insight Pub Date : 2024-06-01 Epub Date: 2024-03-05 DOI: 10.1016/j.cellin.2024.100161

Irshad Sharafutdinov , Aileen Harrer , Mathias Müsken , Klemens Rottner , Heinrich Sticht , Christian Täger , Michael Naumann , Nicole Tegtmeyer , Steffen Backert

{"title":"Cortactin-dependent control of Par1b-regulated epithelial cell polarity in Helicobacter infection","authors":"Irshad Sharafutdinov , Aileen Harrer , Mathias Müsken , Klemens Rottner , Heinrich Sticht , Christian Täger , Michael Naumann , Nicole Tegtmeyer , Steffen Backert","doi":"10.1016/j.cellin.2024.100161","DOIUrl":"10.1016/j.cellin.2024.100161","url":null,"abstract":"<div><p>Cell polarity is crucial for gastric mucosal barrier integrity and mainly regulated by polarity-regulating kinase partitioning-defective 1b (Par1b). During infection, the carcinogen <em>Helicobacter pylori</em> hijacks Par1b via the bacterial oncoprotein CagA leading to loss of cell polarity, but the precise molecular mechanism is not fully clear. Here we discovered a novel function of the actin-binding protein cortactin in regulating Par1b, which forms a complex with cortactin and the tight junction protein zona occludens-1 (ZO-1). We found that serine phosphorylation at S405/418 and the SH3 domain of cortactin are important for its interaction with both Par1b and ZO-1. Cortactin knockout cells displayed disturbed Par1b cellular localization and exhibited morphological abnormalities that largely compromised transepithelial electrical resistance, epithelial cell polarity, and apical microvilli. <em>H. pylori</em> infection promoted cortactin/Par1b/ZO-1 abnormal interactions in the tight junctions in a CagA-dependent manner. Infection of human gastric organoid-derived mucosoids supported these observations. We therefore hypothesize that CagA disrupts gastric epithelial cell polarity by hijacking cortactin, and thus Par1b and ZO-1, suggesting a new signaling pathway for the development of gastric cancer by <em>Helicobacter</em>.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 3","pages":"Article 100161"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000166/pdfft?md5=b780b245a0d10298a9ea435fb1f6c10e&pid=1-s2.0-S2772892724000166-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140270019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innate immune signal transduction pathways to fungal infection: Components and regulation 真菌感染的先天免疫信号转导途径：成分与调节

Cell insight Pub Date : 2024-06-01 Epub Date: 2024-02-10 DOI: 10.1016/j.cellin.2024.100154

Tian Chen , Chengjiang Gao

{"title":"Innate immune signal transduction pathways to fungal infection: Components and regulation","authors":"Tian Chen , Chengjiang Gao","doi":"10.1016/j.cellin.2024.100154","DOIUrl":"https://doi.org/10.1016/j.cellin.2024.100154","url":null,"abstract":"<div><p><em>Candida</em> species are significant causes of mucosal and systemic infections in immune compromised populations, including HIV-infected individuals and cancer patients. Drug resistance and toxicity have limited the use of anti-fungal drugs. A good comprehension of the nature of the immune responses to the pathogenic fungi will aid in the developing of new approaches to the treatment of fungal diseases. In recent years, extensive research has been done to understand the host defending systems to fungal infections. In this review, we described how pattern recognition receptors senses the cognate fungal ligands and the cellular and molecular mechanisms of anti-fungal innate immune responses. Furthermore, particular focus is placed on how anti-fungal signal transduction cascades are being activated for host defense and being modulated to better treat the infections in terms of immunotherapy. Understanding the role that these pathways have in mediating host anti-fungal immunity will be crucial for future therapeutic development.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 3","pages":"Article 100154"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000099/pdfft?md5=d4276ae414de9b9ba8958cee89aa85d4&pid=1-s2.0-S2772892724000099-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140030102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LUC7L3 is a downstream factor of SRSF1 and prevents genomic instability LUC7L3 是 SRSF1 的下游因子，可防止基因组不稳定

Cell insight Pub Date : 2024-06-01 Epub Date: 2024-03-23 DOI: 10.1016/j.cellin.2024.100170

Xiaqing Zhang , Jing Guo , Xin Shi , Xin Zhou , Qiang Chen

{"title":"LUC7L3 is a downstream factor of SRSF1 and prevents genomic instability","authors":"Xiaqing Zhang , Jing Guo , Xin Shi , Xin Zhou , Qiang Chen","doi":"10.1016/j.cellin.2024.100170","DOIUrl":"10.1016/j.cellin.2024.100170","url":null,"abstract":"<div><p>The RNA-binding protein LUC7L3 is the human homolog of yeast U1 small nuclear RNA (snRNA)-related splicing factor Luc7p. While the primary function of LUC7L3 as an RNA-binding protein is believed to be involved in RNA metabolism, particularly in the splicing process, its exact role and other functions are still not fully understood. In this study, we aimed to elucidate the role of LUC7L3 and its impact on cell proliferation. Our study revealed that LUC7L3 depletion impairs cell proliferation compared to the other Luc7p paralogs, resulting in cell apoptosis and senescence. We explored the underlying mechanisms and found that LUC7L3 depletion leads to R-loop accumulation, DNA replication stress, and genome instability. Furthermore, we discovered that LUC7L3 depletion caused abnormalities in spindle assembly, leading to the formation of multinuclear cells. This was attributed to the dysregulation of protein translation of spindle-associated proteins. Additionally, we investigated the interplay between LUC7L3 and SRSF1 and identified SRSF1 as an upper stream regulator of LUC7L3, promoting the translation of LUC7L3 protein. These findings highlight the importance of LUC7L3 in maintaining genome stability and its relationship with SRSF1 in this regulatory pathway.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 3","pages":"Article 100170"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000257/pdfft?md5=92373ec7e69bb4abff4fc8655df333ae&pid=1-s2.0-S2772892724000257-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140272330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 封面

Cell insight Pub Date : 2024-06-01 Epub Date: 2024-06-04 DOI: 10.1016/S2772-8927(24)00026-9

引用次数: 0

STING guides the STX17-SNAP29-VAMP8 complex assembly to control autophagy STING 引导 STX17-SNAP29-VAMP8 复合物组装以控制自噬

Cell insight Pub Date : 2024-04-01 Epub Date: 2024-02-02 DOI: 10.1016/j.cellin.2024.100147

Xiaoyu Song , Yufeng Xi , Ming Dai , Tao Li , Shihao Du , Yuxin Zhu , Mengjie Li , Yunze Li , Siqi Liu , Xia Ding , Xuebiao Yao , Ying Lai , Xing Liu

{"title":"STING guides the STX17-SNAP29-VAMP8 complex assembly to control autophagy","authors":"Xiaoyu Song , Yufeng Xi , Ming Dai , Tao Li , Shihao Du , Yuxin Zhu , Mengjie Li , Yunze Li , Siqi Liu , Xia Ding , Xuebiao Yao , Ying Lai , Xing Liu","doi":"10.1016/j.cellin.2024.100147","DOIUrl":"https://doi.org/10.1016/j.cellin.2024.100147","url":null,"abstract":"<div><p>The stimulator of interferon genes (STING) plays a pivotal role in orchestrating innate immunity, and dysregulated activity of STING has been implicated in the pathogenesis of autoimmune diseases. Recent findings suggest that bacterial infection activates STING, relieving ER stress, and triggers non-canonical autophagy by spatially regulating STX17. Despite these insights, the precise mechanism governing the dynamics of autophagosome fusion elicited by STING remains unclear. In this study, we demonstrate that dynamic STING activation guides the autophagy flux, mirroring the trajectory of canonical autophagy adaptors. STING engages in a physical interaction with STX17, and agonist-induced phosphorylation or degradation alleviates STING's inhibitory effects on the assembly of the STX17-SNAP29-VAMP8 complex. Consistent with these findings, degradation-deficient mutants hinder autophagy flux by impeding STX17-mediated autophagosome-lysosome fusion. Moreover, STING mutants associated with lupus disrupt the assembly of the STX17-SNAP29-VAMP8 complex and autophagy process, which lead to persistent STING activation and elevated IFN-β production. Our results highlight that the intracellular trajectory of STING, coupled with autophagy flux, guides the assembly and membrane fusion of the STX17-SNAP29-VAMP8 complex, ensuring the accurate regulation of innate immunity.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 2","pages":"Article 100147"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000026/pdfft?md5=13bcefa9ef33609bfc3d346390db259f&pid=1-s2.0-S2772892724000026-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139675394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NSD family proteins: Rising stars as therapeutic targets NSD 家族蛋白：作为治疗靶点的新星

Cell insight Pub Date : 2024-04-01 Epub Date: 2024-02-03 DOI: 10.1016/j.cellin.2024.100151

Lin He , Yiping Cao , Luyang Sun

{"title":"NSD family proteins: Rising stars as therapeutic targets","authors":"Lin He , Yiping Cao , Luyang Sun","doi":"10.1016/j.cellin.2024.100151","DOIUrl":"https://doi.org/10.1016/j.cellin.2024.100151","url":null,"abstract":"<div><p>Epigenetic modifications, including DNA methylation and histone post-translational modifications, intricately regulate gene expression patterns by influencing DNA accessibility and chromatin structure in higher organisms. These modifications are heritable, are independent of primary DNA sequences, undergo dynamic changes during development and differentiation, and are frequently disrupted in human diseases. The reversibility of epigenetic modifications makes them promising targets for therapeutic intervention and drugs targeting epigenetic regulators (e.g., tazemetostat, targeting the H3K27 methyltransferase EZH2) have been applied in clinical therapy for multiple cancers. The NSD family of H3K36 methyltransferase enzymes—including NSD1 (KMT3B), NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1)—are now receiving drug development attention, with the exciting advent of an NSD2 inhibitor (KTX-1001) advancing to Phase I clinical trials for relapsed or refractory multiple myeloma. NSD proteins recognize and catalyze methylation of histone lysine marks, thereby regulating chromatin integrity and gene expression. Multiple studies have implicated NSD proteins in human disease, noting impacts from translocations, aberrant expression, and various dysfunctional somatic mutations. Here, we review the biological functions of NSD proteins, epigenetic cooperation related to NSD proteins, and the accumulating evidence linking these proteins to developmental disorders and tumorigenesis, while additionally considering prospects for the development of innovative epigenetic therapies.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 2","pages":"Article 100151"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000063/pdfft?md5=55b4fd9afbcc6158fe06006158b68116&pid=1-s2.0-S2772892724000063-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139719468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0