生物学最新文献

{"title":"Single nuclear RNA sequencing and analysis of basal cells in pulmonary acute respiratory distress syndrome.","authors":"Haoran Chen, Xiaobing Chen, Jinqiu Ding, Haoyue Xue, Xinyi Tang, Xiaomin Li, Yongpeng Xie","doi":"10.1016/j.gene.2024.149131","DOIUrl":"10.1016/j.gene.2024.149131","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to find the gene expression profile specifically in basal cells from pulmonary acute respiratory distress syndrome (ARDSp) patients using single-cell level analysis.</p><p><strong>Methods: </strong>Single nuclear RNA sequencing (snRNA-seq) data of lung samples, including 18 ARDSp participants and 7 healthy participants, were sourced from the GEO database (GSE171524). The differentially expressed genes (DEGs) were screened by | log2FC | >1 and P < 0.05. Functional enrichment was constructed via Gene Ontology (GO) analysis. Pathway enrichment was conducted via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The protein-protein interaction (PPI) network of the DEGs was performed via the STRING database. Cytoscape software was employed to find hub genes. The hub genes were sequenced and validated via data set after constructing the rat model of ARDSp.</p><p><strong>Results: </strong>Using DESeq2 package, 299 genes were disclosed to be downregulated, while 228 were upregulated in ARDSp participants. GO analysis disclosed DEGs were enriched in processes like actin filament organization, regulation of small GTPase-mediated signal transduction, response to unfolded protein, wound healing, and response to oxygen levels. Meanwhile, KEGG analysis disclosed DEGs were involved in protein digestion and absorption, Th17 cell differentiation, iron death, and other biological effects. Ten hub genes, including FN1, HIF1A, HSP90AA1, SMAD3, FOS, CDKN2A, COL1A1, HSPA8, FLNA, and NFKBIA were highlighted based on their network centrality and biological significance. HIF1A, HSPA8, NFKBIA, and CDKN2A were differentially expressed in the validation dataset.</p><p><strong>Conclusions: </strong>Basal cells in ARDSp exhibit significant changes in gene expression, with ten hub genes identified. Among them, four (HIF1A, HSPA8, NFKBIA, CDKN2A) were validated experimentally using RNA-Seq data from an ARDSp rat model. This study emphasizes the role of basal cells in ARDSp, highlighting the altered gene networks involved in repair and inflammatory responses, providing potential targets for further therapeutic exploration. These findings suggest that alterations in these hub genes may be crucial to basal cell-driven inflammatory and reparative responses in ARDSp.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"149131"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Regulation of cell proliferation and migration in gallbladder cancer by zinc finger X-chromosomal protein\" [528(2) (2013) 261-266].","authors":"Zhujun Tan, Shenglai Zhang, Maolan Li, Xiangsong Wu, Hao Weng, Qian Ding, Yang Cao, Runfa Bao, Yijun Shu, Jiasheng Mu, Qichen Ding, Wenguang Wu, Jiahua Yang, Lin Zhang, Yingbin Liu","doi":"10.1016/j.gene.2024.149113","DOIUrl":"10.1016/j.gene.2024.149113","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149113"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life lipid overload in Native American Myopathy is phenocopied by stac3 knockout in zebrafish.","authors":"Rajashekar Donaka, Houfeng Zheng, Cheryl L Ackert-Bicknell, David Karasik","doi":"10.1016/j.gene.2024.149123","DOIUrl":"10.1016/j.gene.2024.149123","url":null,"abstract":"<p><p>Understanding the early stages of human congenital myopathies is critical for proposing strategies for improving musculoskeletal muscle performance, such as restoring the functional integrity of the cytoskeleton. SH3 and cysteine-rich domain 3 (STAC3) are proteins involved in nutrient regulation and are an essential component of the excitation-contraction (EC) coupling machinery for Ca²⁺ releasing. A mutation in STAC3 causes debilitating Native American Myopathy (NAM) in humans, while loss of this gene in mice and zebrafish (ZF) results in premature death. Clinically, NAM patients demonstrated increased lipids in skeletal muscle, but it is unclear if neutral lipids are associated with altered muscle function in NAM. Using a CRISPR/Cas9 induced stac3^-/- knockout (KO) zebrafish model, we determined that loss of stac3 leads to delayed larval hatching which corresponds with muscle weakness and decreased whole-body Ca²⁺ level during early skeletal development. Specifically, we observed defects in the cytoskeleton in F-actin and slow muscle fibers at 5 and 7 days post-fertilizations (dpf). Myogenesis regulators such as myoD and myf5, mstnb were significantly altered in stac3^-/- larvae. These muscle alterations were associated with elevated neutral lipid levels starting at 5 dpf and persisting beyond 7 dpf. Larva lacking stac3 had reduced viability with no larva knockouts surviving past 11 dpf. This data suggests that our stac3^-/- zebrafish serve as an alternative model to study the diminished muscle function seen in NAM patients. The data gathered from this new model over time supports a mechanistic view of lipotoxicity as a critical part of the pathology of NAM and the associated loss of function in muscle.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149123"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142727577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"c.640-814T>C mutation in deep intronic region of alpha-galactosidase A gene is associated with Fabry disease via dominant-negative effect.","authors":"Piyi Zhang, Yongxiang Wang, Gaxue Jiang, Yiming Zhang, Yonglin Chen, Yu Peng, Zixian Chen, Ming Bai","doi":"10.1016/j.gene.2024.149127","DOIUrl":"10.1016/j.gene.2024.149127","url":null,"abstract":"<p><p>Fabry disease (FD) is a lysosomal storage disorder resulting from mutations in the alpha-galactosidase A (GLA) gene, characterized by pain, skin lesions, renal failure, and cardiac disease. A 60-year-old proband was hospitalized for recurrent atrial fibrillation (AF) that was unresponsive to medication, with cardiac magnetic resonance imaging (CMRI) revealing left ventricular wall hypertrophy and fat infiltration. Whole-exome sequencing (WES) did not reveal any suspicious pathogenic variants. To further assess the diagnosis, endomyocardial biopsy (EMB) and electron microscopy were performed, revealing abundant zebra bodies in cardiomyocytes, consistent with FD. The diagnosis was ultimately confirmed by GLA enzyme activity analysis (<1.00). Further genetic investigations identified a deep intronic variant (c.640-814T>C) within the GLA gene. Minigene experiments demonstrated that this variant affected the splicing of GLA, resulting in the production of a truncated protein (p.Pro214SerfsTer10). Western blotting (WB) showed that the truncated protein was retained, while immunofluorescence (IF) analysis indicated partial lysosomal localization. In vitro assays confirmed that the retained protein was non-functional and exerted a dominant-negative effect on the normal GLA protein. Molecular docking analysis further revealed that the truncated protein could bind to the wild GLA monomer, significantly reducing cellular GLA enzyme activity. These findings indicate that, beyond being non-functional, the c.640-814T>C mutation may also exerts a dominant-negative effect that impairs the function of the wild GLA protein. These results highlight the importance of recognizing deep intronic mutations in the diagnosis and treatment of FD, contributing to a deeper understanding of the molecular mechanisms, enriching mutation databases, and providing insights into genotype-phenotype correlations.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149127"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis of key genes and signaling pathways in sepsis-associated intestinal mucosal barrier damage.","authors":"Zhao Gao, Zhiyuan Gong, Hai Huang, Xuemeng Ren, Zhenlu Li, Peng Gao","doi":"10.1016/j.gene.2024.149137","DOIUrl":"10.1016/j.gene.2024.149137","url":null,"abstract":"<p><strong>Objectives: </strong>The aim is to analyze differentially expressed genes (DEGs) in mice with sepsis-related intestinal mucosal barrier damage and to explore the diagnostic and protective mechanisms of this condition at the transcriptome level.</p><p><strong>Methods: </strong>Small intestinal tissues from healthy male C57BL/6J mice subjected to Cecal ligation and puncture (CLP) and sham operation were collected. High-throughput sequencing was performed using the paired-end sequencing mode of the Illumina HiSeq platform. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted on the differentially expressed genes (DEGs). A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified with Cytoscape. These hub genes were then validated using quantitative real-time polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>A total of 239 DEGs were identified, with 49 upregulated and 130 downregulated genes. KEGG enrichment analysis showed that these DEGs were primarily involved in cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, viral protein interactions with cytokines and their receptors, and the IL-17 signaling pathway. The top 10 hub genes were selected using the cytoHubba plugin. Experimental validation confirmed that the expression levels of TBX21, CSF3, IL-6, CXCR3, and CXCL9 matched the sequencing results.</p><p><strong>Conclusion: </strong>TBX21, CSF3, IL-6,CXCR3, and CXCL9 may be potential biological markers for the diagnosis and treatment the sepsis-associated intestinal mucosal barrier.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"149137"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Transcriptome analysis to identify key genes involved in terpenoid and rosmarinic acid biosynthesis in lemon balm (Melissa officinalis)\" [Gene 773 (2021) 145417].","authors":"Mehdi Mansouri, Fatemeh Mohammadi","doi":"10.1016/j.gene.2024.149114","DOIUrl":"10.1016/j.gene.2024.149114","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149114"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An eGFP-Col4a2 mouse model reveals basement membrane dynamics underlying hair follicle morphogenesis.","authors":"Duligengaowa Wuergezhen, Eleonore Gindroz, Ritsuko Morita, Kei Hashimoto, Takaya Abe, Hiroshi Kiyonari, Hironobu Fujiwara","doi":"10.1083/jcb.202404003","DOIUrl":"10.1083/jcb.202404003","url":null,"abstract":"<p><p>Precisely controlled remodeling of the basement membrane (BM) is crucial for morphogenesis, but its molecular and tissue-level dynamics, underlying mechanisms, and functional significance in mammals remain largely unknown due to limited visualization tools. We developed mouse lines in which the endogenous collagen IV gene (Col4a2) was fused with a fluorescent tag. Through live imaging of developing hair follicles, we reveal a spatial gradient in the turnover rate of COL4A2 that is closely coupled with both the BM expansion rate and the proliferation rate of epithelial progenitors. Epithelial progenitors are displaced with directionally expanding BMs but do not actively migrate on stationary BM. The addition of a matrix metalloproteinase inhibitor delays COL4A2 turnover, restrains BM expansion, and increases perpendicular divisions of epithelial progenitors, altering hair follicle morphology. Our findings highlight the spatially distinct dynamics of BM and their key roles in orchestrating progenitor cell behavior and organ shape during development.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 proteome-wide yeast degron collection for the dynamic study of protein function.","authors":"Rosario Valenti, Yotam David, Dunya Edilbi, Benjamin Dubreuil, Angela Boshnakovska, Yeynit Asraf, Tomer-Meir Salame, Ehud Sass, Peter Rehling, Maya Schuldiner","doi":"10.1083/jcb.202409050","DOIUrl":"https://doi.org/10.1083/jcb.202409050","url":null,"abstract":"<p><p>Genome-wide collections of yeast strains, known as libraries, revolutionized the way systematic studies are carried out. Specifically, libraries that involve a cellular perturbation, such as the deletion collection, have facilitated key biological discoveries. However, short-term rewiring and long-term accumulation of suppressor mutations often obscure the functional consequences of such perturbations. We present the AID library which supplies \"on demand\" protein depletion to overcome these limitations. Here, each protein is tagged with a green fluorescent protein (GFP) and an auxin-inducible degron (AID), enabling rapid protein depletion that can be quantified systematically using the GFP element. We characterized the degradation response of all strains and demonstrated its utility by revisiting seminal yeast screens for genes involved in cell cycle progression as well as mitochondrial distribution and morphology. In addition to recapitulating known phenotypes, we also uncovered proteins with previously unrecognized roles in these central processes. Hence, our tool expands our knowledge of cellular biology and physiology by enabling access to phenotypes that are central to cellular physiology and therefore rapidly equilibrated.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth-dependent concentration gradient of the oscillating Min system in Escherichia coli.","authors":"Claudia Morais Parada, Ching-Cher Sanders Yan, Cheng-Yu Hung, I-Ping Tu, Chao-Ping Hsu, Yu-Ling Shih","doi":"10.1083/jcb.202406107","DOIUrl":"10.1083/jcb.202406107","url":null,"abstract":"<p><p>Cell division in Escherichia coli is intricately regulated by the MinD and MinE proteins, which form oscillatory waves between cell poles. These waves manifest as concentration gradients that reduce MinC inhibition at the cell center, thereby influencing division site placement. This study explores the plasticity of the MinD gradients resulting from the interdependent interplay between molecular interactions and diffusion in the system. Through live cell imaging, we observed that as cells elongate, the gradient steepens, the midcell concentration decreases, and the oscillation period stabilizes. A one-dimensional model investigates kinetic rate constants representing various molecular interactions, effectively recapitulating our experimental findings. The model reveals the nonlinear dynamics of the system and a dynamic equilibrium among these constants, which underlie variable concentration gradients in growing cells. This study enhances quantitative understanding of MinD oscillations within the cellular environment. Furthermore, it emphasizes the fundamental role of concentration gradients in cellular processes.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-canonical CDK6 activity promotes cilia disassembly by suppressing axoneme polyglutamylation.","authors":"Kai He, Xiaobo Sun, Chuan Chen, San Luc, Jielu Hao Robichaud, Yingyi Zhang, Yan Huang, Biyun Ji, Pei-I Ku, Radhika Subramanian, Kun Ling, Jinghua Hu","doi":"10.1083/jcb.202405170","DOIUrl":"10.1083/jcb.202405170","url":null,"abstract":"<p><p>Tubulin polyglutamylation is a posttranslational modification that occurs primarily along the axoneme of cilia. Defective axoneme polyglutamylation impairs cilia function and has been correlated with ciliopathies, including Joubert Syndrome (JBTS). However, the precise mechanisms regulating proper axoneme polyglutamylation remain vague. Here, we show that cyclin-dependent kinase 6 (CDK6), but not its paralog CDK4, localizes to the cilia base and suppresses axoneme polyglutamylation by phosphorylating RAB11 family interacting protein 5 (FIP5) at site S641, a critical regulator of cilia import of glutamylases. S641 phosphorylation disrupts the ciliary recruitment of FIP5 and its association with RAB11, thereby reducing the ciliary import of glutamylases. Encouragingly, the FDA-approved CDK4/6 inhibitor Abemaciclib can effectively restore cilia function in JBTS cells with defective glutamylation. In summary, our study elucidates the regulatory mechanisms governing axoneme polyglutamylation and suggests that developing CDK6-specific inhibitors could be a promising therapeutic strategy to enhance cilia function in ciliopathy patients.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}