Cell insightPub Date : 2024-10-01Epub Date: 2024-07-19DOI: 10.1016/j.cellin.2024.100193
Qiankun Wang , Liang Shan
{"title":"Role of the CARD8 inflammasome in HIV pathogenesis","authors":"Qiankun Wang , Liang Shan","doi":"10.1016/j.cellin.2024.100193","DOIUrl":"10.1016/j.cellin.2024.100193","url":null,"abstract":"<div><p>Human immunodeficiency virus (HIV) continues to be a significant global health challenge despite decades of research and advances in treatment. Substantial gaps in our understanding of the mechanisms of HIV pathogenesis and the host immune responses still exist. The interaction between HIV and these immune responses is pivotal in the disease progression to acquired immunodeficiency syndrome (AIDS). Recently, the caspase recruitment domain-containing protein 8 (CARD8) inflammasome has emerged as a crucial factor in orchestrating innate immune responses to HIV infection and exerting a substantial impact on viral pathogenesis. CARD8 restricts viral replication by detecting the activity of HIV protease. Conversely, it also contributes to the depletion of CD4<sup>+</sup> T cells, a key feature of disease progression towards AIDS. The purpose of this review is to summarize the role of the CARD8 inflammasome in HIV pathogenesis, delving into its mechanisms of action and potential implications for the development of therapeutic strategies.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 5","pages":"Article 100193"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000488/pdfft?md5=db72195e8e4be00589a164a2210e8966&pid=1-s2.0-S2772892724000488-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141848303","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}
Cell insightPub Date : 2024-10-01Epub Date: 2024-07-14DOI: 10.1016/j.cellin.2024.100184
Marxa L. Figueiredo , Sagar Utturkar , Shreya Kumar , Carlos Eduardo Fonseca-Alves
{"title":"Transcriptomic analysis of mouse TRAMP cell lines and tumors provide insights into shared pathways and therapeutic targets","authors":"Marxa L. Figueiredo , Sagar Utturkar , Shreya Kumar , Carlos Eduardo Fonseca-Alves","doi":"10.1016/j.cellin.2024.100184","DOIUrl":"10.1016/j.cellin.2024.100184","url":null,"abstract":"<div><p>The present study focused on comparing the gene expression profiles of different mouse models of prostate cancer, focusing on the TRAMP transgenic model and its derived cell lines and extending the comparisons to relevant genetically engineered mouse models and human prostate cancer datasets. Employing RNA sequencing, we examined different levels of prostate cancer aggressiveness from the original TRAMP cells to the TRAMP-C2 (TC2) derived cell line and extending to the aggressive TC2-Ras (TC2R) cells and tumors. TC2R acquire the ability to grow in bone tissue upon implantation, unlike the parental TC2 cells. Analysis identified upregulated genes in cell cycle regulation, immune response, and mitotic processes in TRAMP compared to wild-type tissues. TC2 cells exhibited unique gene profiles enriched in ECM organization and tissue development pathways, while TC2R cells showed increased cytokine signaling and motility genes, with decreased ECM and immune response pathways. <em>In vivo</em> TC2R models demonstrated enhanced ECM organization and receptor tyrosine kinase signaling in tumors, notably enriching immune processes and collagen degradation pathways in intratibial tumors. Comparative analysis among mouse and human datasets showed overlaps, particularly in pathways relating to mitotic cycle regulation, ECM organization, and immune interactions. A gene signature identified in TC2R tumors correlated with aggressive tumor behavior and poor survival in human datasets. Further immune cell landscape analysis of TC2R tumors revealed altered T cell subsets and macrophages, confirmed in single-cell RNA-seq from human samples. TC2R models thus hold significant promise in helping advance preclinical therapeutics, potentially contributing to improved prostate cancer patient outcomes.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 5","pages":"Article 100184"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000397/pdfft?md5=4524069e2dbfa3aa662ff78d8038cbac&pid=1-s2.0-S2772892724000397-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141715513","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}
Cell insightPub Date : 2024-10-01Epub Date: 2024-08-05DOI: 10.1016/j.cellin.2024.100194
Tomoyasu Sugiyama
{"title":"Finding new roles of classic biomolecular condensates in the nucleus: Lessons from fission yeast","authors":"Tomoyasu Sugiyama","doi":"10.1016/j.cellin.2024.100194","DOIUrl":"10.1016/j.cellin.2024.100194","url":null,"abstract":"<div><p>Decades have passed since the initial discovery of membrane-less nuclear compartments, commonly called nuclear bodies or nuclear condensates. These compartments have drawn attention to their unique characteristics and functions, especially after introducing \"liquid-liquid phase separation\" to this research field. While the majority of the studies on nuclear condensates have been conducted in multicellular organisms, recent genetic, biochemical, and cell biological analyses using the fission yeast <em>Schizosaccharomyces pombe</em> have yielded valuable insights into biomolecular condensates. This review article focuses on two 'classic' nuclear condensates and discusses how research using fission yeast has unveiled previously unknown functions of these known nuclear bodies.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 5","pages":"Article 100194"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277289272400049X/pdfft?md5=c0d8ed3e8c65d10e7a2ab263d8d5bc3e&pid=1-s2.0-S277289272400049X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141979922","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}
Cell insightPub Date : 2024-10-01Epub Date: 2024-07-14DOI: 10.1016/j.cellin.2024.100183
Rong Luo , Jiannan Wu , Xueman Chen , Yulan Liu , Dequan Liu , Erwei Song , Man-Li Luo
{"title":"ATR/Chk1 interacting lncRNA modulates DNA damage response to induce breast cancer chemoresistance","authors":"Rong Luo , Jiannan Wu , Xueman Chen , Yulan Liu , Dequan Liu , Erwei Song , Man-Li Luo","doi":"10.1016/j.cellin.2024.100183","DOIUrl":"10.1016/j.cellin.2024.100183","url":null,"abstract":"<div><p>The ATR-Chk1 pathway is essential in cellular responses to DNA damage and replication stress, whereas the role of long noncoding RNAs (lncRNAs) in regulating this pathway remains largely unknown. In this study, we identify an ATR and Chk1 interacting lncRNA (ACIL, also known as LRRC75A-AS1 or SNHG29), which promotes the phosphorylation of Chk1 by ATR upon DNA damages. High ACIL levels are associated with chemoresistance to DNA damaging agents and poor outcome of breast cancer patients. ACIL knockdown sensitizes breast cancer cells to DNA damaging drugs <em>in vitro</em> and <em>in vivo</em>. ACIL protects cancer cells against DNA damages by inducing cell cycle arrest, stabilizing replication forks and inhibiting unscheduled origin firing, thereby guarding against replication catastrophe and contributing to DNA damage repair. These findings demonstrate a lncRNA-dependent mechanism of activating the ATR-Chk1 pathway and highlight the potential of utilizing ACIL as a predictive biomarker for chemotherapy sensitivity, as well as targeting ACIL to reverse chemoresistance in breast cancer.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 5","pages":"Article 100183"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000385/pdfft?md5=6755b14d725e10ac0eeb2f6f35905bc8&pid=1-s2.0-S2772892724000385-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141695249","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}
Cell insightPub Date : 2024-08-01Epub Date: 2024-07-02DOI: 10.1016/j.cellin.2024.100181
Ahmad Jawad Sabir , Lijun Rong , Christopher C. Broder , Moushimi Amaya
{"title":"Cedar virus biology and its applications as a surrogate for highly pathogenic henipaviruses","authors":"Ahmad Jawad Sabir , Lijun Rong , Christopher C. Broder , Moushimi Amaya","doi":"10.1016/j.cellin.2024.100181","DOIUrl":"10.1016/j.cellin.2024.100181","url":null,"abstract":"<div><p>Nipah Virus (NiV) and Hendra Virus (HeV), are the prototype species of the genus <em>Henipavirus</em> and are highly pathogenic agents capable of causing fatal diseases in both animals and humans. Both NiV and HeV are classified as biosafety level-4 (BSL-4) restricted pathogens and remain the only henipaviruses within the genus known to cause systemic, severe respiratory and encephalitic henipaviral disease, and represent substantial transboundary threats. There are no approved prophylactic or therapeutic treatments for human henipavirus infections, and the World Health Organization acknowledges them as priority pathogens needing urgent research. The discovery of Cedar virus (CedV), the only recognized non-pathogenic henipavirus, has provided a number of unique opportunities to study henipavirus and host interactions and also facilitate countermeasure development research at lower BSL-2 containment. This review will highlight the unique aspects of CedV biology and how it has been exploited as a model for developing therapeutic strategies against more virulent henipavirus species.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 4","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000361/pdfft?md5=0595314a62733ce59358b6e4a7a0c2ab&pid=1-s2.0-S2772892724000361-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141630883","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}
Cell insightPub Date : 2024-08-01Epub Date: 2024-06-27DOI: 10.1016/j.cellin.2024.100180
Liwen Jiang , Linfeng Huang , Wei Jiang
{"title":"H3K27me3-mediated epigenetic regulation in pluripotency maintenance and lineage differentiation","authors":"Liwen Jiang , Linfeng Huang , Wei Jiang","doi":"10.1016/j.cellin.2024.100180","DOIUrl":"https://doi.org/10.1016/j.cellin.2024.100180","url":null,"abstract":"<div><p>Cell fate determination is an intricate process which is orchestrated by multiple regulatory layers including signal pathways, transcriptional factors, epigenetic modifications, and metabolic rewiring. Among the sophisticated epigenetic modulations, the repressive mark H3K27me3, deposited by PRC2 (polycomb repressive complex 2) and removed by demethylase KDM6, plays a pivotal role in mediating the cellular identity transition through its dynamic and precise alterations. Herein, we overview and discuss how H3K27me3 and its modifiers regulate pluripotency maintenance and early lineage differentiation. We primarily highlight the following four aspects: 1) the two subcomplexes PRC2.1 and PRC2.2 and the distribution of genomic H3K27 methylation; 2) PRC2 as a critical regulator in pluripotency maintenance and exit; 3) the emerging role of the eraser KDM6 in early differentiation; 4) newly identified additional factors influencing H3K27me3. We present a comprehensive insight into the molecular principles of the dynamic regulation of H3K27me3, as well as how this epigenetic mark participates in pluripotent stem cell-centered cell fate determination.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 4","pages":"Article 100180"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277289272400035X/pdfft?md5=5fde7f4c838766c83f6029073026497b&pid=1-s2.0-S277289272400035X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141543449","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}
Cell insightPub Date : 2024-08-01Epub Date: 2024-07-04DOI: 10.1016/j.cellin.2024.100182
Xiaoyu Zhang , Jian Wang , Wangxin Guo , Hongjiong Zhang , Bin Zhou , Chen Yu , Dong Gao
{"title":"The cell fates of intermediate cell population in prostate development","authors":"Xiaoyu Zhang , Jian Wang , Wangxin Guo , Hongjiong Zhang , Bin Zhou , Chen Yu , Dong Gao","doi":"10.1016/j.cellin.2024.100182","DOIUrl":"https://doi.org/10.1016/j.cellin.2024.100182","url":null,"abstract":"<div><p>Organ development, regeneration and cancer initiation are typically influenced by the proliferation and lineage plasticity of tissue-specific stem cells. Prostate intermediate cells, which exhibit characteristics of both basal and luminal cells, are prevalent in pathological states and during organ development. However, the identity, fate and function of these intermediate cells in prostate development are not well understood. Through single-cell RNA-seq analysis on neonatal urogenital sinus tissue, we identified intermediate cells exhibiting stem cell potential. A notable decline in the population of intermediate cells was observed during prostate development. Prostate intermediate cells were specifically labeled in early and late postnatal development by the enhanced dual-recombinase-mediated genetic tracing systems. Our findings revealed that these cells possess significant stem cell capabilities as demonstrated in organoid formation and cell fate mapping assays. These intermediate cells also exhibited intrinsic bipotential properties, enabling them to differentiate into both basal and luminal cells. Additionally, we discovered a novel transition from intermediate cell expressing neuroendocrine markers to neuroendocrine cell during prostate development. This study highlights intermediate cells as a crucial stem cell population and enhances our understanding of their role in prostate development and the plasticity of prostate cancer lineage.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 4","pages":"Article 100182"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000373/pdfft?md5=1be553b77f3c68110f3368aed46e5a2b&pid=1-s2.0-S2772892724000373-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141594865","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}
Cell insightPub Date : 2024-08-01Epub Date: 2024-06-15DOI: 10.1016/j.cellin.2024.100178
Rong Hua , Kaitao Zhao , Zaichao Xu , Yingcheng Zheng , Chuanjian Wu , Lu Zhang , Yan Teng , Jingjing Wang , Mengfei Wang , Jiayu Hu , Lang Chen , Detian Yuan , Wei Dong , Xiaoming Cheng , Yuchen Xia
{"title":"Stratifin-mediated activation of AKT signaling and therapeutic targetability in hepatocellular carcinoma progression","authors":"Rong Hua , Kaitao Zhao , Zaichao Xu , Yingcheng Zheng , Chuanjian Wu , Lu Zhang , Yan Teng , Jingjing Wang , Mengfei Wang , Jiayu Hu , Lang Chen , Detian Yuan , Wei Dong , Xiaoming Cheng , Yuchen Xia","doi":"10.1016/j.cellin.2024.100178","DOIUrl":"10.1016/j.cellin.2024.100178","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and presents a significant threat to human health. Despite its prevalence, the underlying regulatory mechanisms of HCC remain unclear. In this study, we integrated RNA-seq datasets, proteome dataset and survival analysis and unveiled Stratifin (SFN) as a potential prognostic biomarker for HCC. SFN knockdown inhibited HCC progression in cell cultures and mouse models. Conversely, ectopic expression of Sfn in primary mouse HCC model accelerated HCC progression. Mechanistically, SFN acted as an adaptor protein, activating AKT1 signaling by fostering the interaction between PDK1 and AKT1, with the R56 and R129 sites on SFN proving to be crucial for this binding. In the syngeneic implantation model, the R56A/R129A mutant of SFN inhibited Akt signaling activation and impeded HCC growth. Additionally, peptide inhibitors designed based on the binding motif of AKT1 to SFN significantly inhibited HCC progression. In summary, our findings establish that SFN promotes HCC progression by activating AKT signaling through the R56 and R129 binding sites. This discovery opens new avenues for a promising therapeutic strategy for the treatment of HCC.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 4","pages":"Article 100178"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000336/pdfft?md5=a8eb78e9c0e26d11d91f21cb11dd6077&pid=1-s2.0-S2772892724000336-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141403421","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}