Mammalian Genome最新文献_第2页

Single-cell and bulk RNA sequencing reveals specific Trem2 positive B cell subtype niche after myocardial infarction in mice. 单细胞和大量RNA测序揭示了小鼠心肌梗死后Trem2阳性B细胞特异性亚型生态位。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-09-01 Epub Date: 2025-06-16 DOI: 10.1007/s00335-025-10144-w

Xue Qiu, Qiang Wang, Yongyu Chen, Bin Liang, Jiansheng Huang, Yequan Lu, Jianchao Ma, Lang Li

{"title":"Single-cell and bulk RNA sequencing reveals specific Trem2 positive B cell subtype niche after myocardial infarction in mice.","authors":"Xue Qiu, Qiang Wang, Yongyu Chen, Bin Liang, Jiansheng Huang, Yequan Lu, Jianchao Ma, Lang Li","doi":"10.1007/s00335-025-10144-w","DOIUrl":"10.1007/s00335-025-10144-w","url":null,"abstract":"This study aims to characterize B cell subtypes in mice following myocardial infarction (MI) and identify potential therapeutic targets for adverse remodeling post-MI. The scRNA-seq (GSE163129) and bulk RNA sequencing data (GSE19322) of mice post-MI were obtained from the GEO database. Seurat, gene set enrichment analysis, SCENIC analysis, Monocle 2 and NichNet analysis were performed in scRNA-seq data. Only the changes of immune cell populations in the infarct areas at different points after MI and pre - MI (steady - state) condition were compared. Bulk RNA-seq data for myocardium of post-MI in mice was used for validation. Twelve cell types were identified on scRNA-seq data and B cells were divided into five subtypes including B_Trem2 and others. B_Trem2 exhibited regulatory B (Breg) cells characteristics, displaying expressions of the cardiac repair gene Trem2, the anti-inflammatory marker Il10, and the myocardial remodeling molecule Spp1. B_Trem2 activated anti-inflammatory pathways. Nfe2l2, Rxrb, Zfp672, Prdm1 and Hivep3 were activated in the B_Trem2 subtype occupying the terminal stage of B cell development. Apoe was a potential activator of Spp1 overexpression in B_Trem2. Receptors of Apoe, namely Lrp1, Sdc4, and Sdc3, exhibited elevated expression within B_Trem2 subtype. This study identified a specific B cell subtype (B_Trem2) with Breg characteristics that overexpressed Spp1 in post- MI mice. Apoe may promote Spp1 expression in B_Trem2, by binding Apoe to Lrp1, Sdc4 and Sdc3 receptors on B_Trem2. This provides a new therapeutic target for MI.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"735-745"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Snrnp25 is a candidate for the peri-implantation lethal phenotype of the Hba deletions. Snrnp25是Hba缺失的着床期致死性表型的候选基因。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-09-01 Epub Date: 2025-05-21 DOI: 10.1007/s00335-025-10133-z

Ana María Velásquez-Escobar, Andrew E Hillhouse, Terry Magnuson, David W Threadgill

{"title":"Snrnp25 is a candidate for the peri-implantation lethal phenotype of the Hba deletions.","authors":"Ana María Velásquez-Escobar, Andrew E Hillhouse, Terry Magnuson, David W Threadgill","doi":"10.1007/s00335-025-10133-z","DOIUrl":"10.1007/s00335-025-10133-z","url":null,"abstract":"Mutations in adult hemoglobin alpha genes in humans lead to blood disorders commonly known as α-thalassemia. In search of a mouse model for this disease, mutagenesis screens have identified several deletions that resemble these phenotypes. The Hbab2(th) deletion, in particular, replicates the characteristics of alpha-thalassemia minor in heterozygous mice but presents a homozygous embryonic lethal phenotype. Previous analyses of Hbab2(th) mice suggested that the deletion affects both Hba genes (Hba-a1 and Hba-a2) and considered epidermal growth factor receptor (Egfr) or rhomboid 5 homolog 1 (Rhbdf1) to be responsible for the embryonic lethality. Molecular analysis of Hbab2(th) revealed a deletion spanning a 1 cM region of mouse chromosome 11. Importantly, the Hbab2(th) deletion does not extend to Egfr, indicating that the observed lethality of homozygous embryos is not due to the loss of Egfr. Sequence analysis of the Hbab2(th) deletion showed that the Hba-a2 gene is not deleted, but the lack of expression is likely due to the disruption of upstream regulatory regions. Furthermore, we identify Snrnp25, which codes for the small nuclear ribonucleoprotein 25 (U11/U12), as the candidate gene most likely responsible for the peri-implantation lethality of Hbab2(th) homozygous mice. These findings enhance the understanding of the genetic mechanisms underlying α-thalassemia and provide insights into novel genes essential for early mammalian development.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"727-734"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic and immune landscape of keratoconus: insights from Mendelian randomization analysis. 圆锥角膜的遗传和免疫景观：来自孟德尔随机化分析的见解。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-09-01 Epub Date: 2025-05-16 DOI: 10.1007/s00335-025-10135-x

Yuhui Yu, Qiang Liu, Chen Zhou, Juan Jiang, Yanchun Li

{"title":"Genetic and immune landscape of keratoconus: insights from Mendelian randomization analysis.","authors":"Yuhui Yu, Qiang Liu, Chen Zhou, Juan Jiang, Yanchun Li","doi":"10.1007/s00335-025-10135-x","DOIUrl":"10.1007/s00335-025-10135-x","url":null,"abstract":"This study aimed to identify key genes and immune features associated with keratoconus (KC), a progressive eye disorder, by integrating genomic and transcriptomic data using Mendelian randomization (MR) methods. We employed summary data-based Mendelian randomization (SMR) and inverse-variance weighted Mendelian randomization (IVW-MR) to analyze genetic variations from public databases. The study included expression quantitative trait loci (eQTL) data for 16,987 genes and GWAS summary statistics for 19,942 gene traits and 731 immune traits. We also utilized gene expression data from keratoconus patients and controls to validate findings and explore causal relationships. We identified 715 genes associated with KC, including 371 risk genes and 344 protective genes. Pathway over-representation analyses indicated that risk genes are involved in the regulation of the cytoskeleton, while protective genes are related to metabolic processes. Differential expression analysis showed significant overexpression of risk genes in KC samples. Additionally, we found 21 immune phenotypes with causal effects on KC, highlighting the role of immune cells in the disease's pathogenesis. The study revealed multiple risk and protective genes linked to KC, providing new insights into its pathophysiological mechanisms. The findings underscore the importance of cytoskeletal remodeling and immune regulation in KC and suggest potential targets for future diagnostic and therapeutic strategies. Further research is needed to validate these genes and immune traits' functions and their clinical application potential.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"859-871"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genomic signatures of selection in drug metabolizing genes across cattle populations. 牛种群中药物代谢基因选择的基因组特征。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-09-01 Epub Date: 2025-06-17 DOI: 10.1007/s00335-025-10139-7

Sonali Sonejita Nayak, Manjit Panigrahi, Ayushi Vaidhya, G Ravi Prakash, Subhashree Parida, Triveni Dutt

{"title":"Genomic signatures of selection in drug metabolizing genes across cattle populations.","authors":"Sonali Sonejita Nayak, Manjit Panigrahi, Ayushi Vaidhya, G Ravi Prakash, Subhashree Parida, Triveni Dutt","doi":"10.1007/s00335-025-10139-7","DOIUrl":"10.1007/s00335-025-10139-7","url":null,"abstract":"Cattle are integral to agriculture and rural livelihoods in India, where diverse indigenous breeds have adapted to varied environments. The diversity of Indian breeds has shaped genetic traits linked to toxin processing, disease resistance, and metabolic efficiency. The genomic study of cattle reveals significant insights into the evolutionary pressures shaping drug-metabolizing genes (DMGs) across breeds. This study analyzed genome-wide selection signatures in seven cattle breeds, including Indigenous such as Red Sindhi (n = 96), Tharparkar (n = 72), Gir (n = 96), crossbred such as Frieswal (n = 14), Vrindavani (n = 72), and exotic cattle populations such as Holstein Friesian (n = 63), Jersey (n = 28). We utilized 50K and ddRAD SNP genotyping data to perform intra-population analyses (iHS, CLR, ROH) and inter-population analyses (FST, XP-EHH) for detecting genomic regions under selection. Key findings include the identification of cytochrome P450 genes (e.g., CYP7A1, CYP4A11, CYP19A1) and other DMGs exhibiting selection signatures linked to metabolic and biosynthetic processes. Red Sindhi cattle exhibited selection in genes like CYP7A1 and CYP2W1, which were involved in steroid biosynthesis and chemical stimulus response. Tharparkar cattle demonstrated positive selection in CYP4A11 and related genes involved in the functionalization of compounds. Crossbreeds of Vrindavani and Frieswal displayed intermediate signatures, reflecting mixed genetic contributions. Our research shows that Indigenous purebred cattle possess a superior selection signature of drug-metabolizing ability, enhanced disease resistance, and greater adaptability than crossbred and exotic breeds. This research contributes to understanding breed-specific adaptations, informing pharmacological interventions and conservation efforts.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"842-858"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elucidation of novel diagnostic biomarkers and therapeutic targets in colorectal carcinoma: an integrative approach leveraging multi-omics, computational biology, and single-cell sequencing technologies. 结直肠癌新的诊断生物标志物和治疗靶点的阐明：利用多组学、计算生物学和单细胞测序技术的综合方法。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-09-01 Epub Date: 2025-06-25 DOI: 10.1007/s00335-025-10141-z

Tingyang Li, Yuhua Tian, Yinchuan Wang, Jianle Yang, Ziyu Chen, Yiliang Li

{"title":"Elucidation of novel diagnostic biomarkers and therapeutic targets in colorectal carcinoma: an integrative approach leveraging multi-omics, computational biology, and single-cell sequencing technologies.","authors":"Tingyang Li, Yuhua Tian, Yinchuan Wang, Jianle Yang, Ziyu Chen, Yiliang Li","doi":"10.1007/s00335-025-10141-z","DOIUrl":"10.1007/s00335-025-10141-z","url":null,"abstract":"This study employs a comprehensive, multi-layered analytical approach to comprehensively investigate the pathogenesis, diagnostic methodologies, and potential therapeutic targets of colorectal cancer. Integrating data from the Global Burden of Disease (GBD) database, transcriptomics, proteomics, and single-cell sequencing technologies, this study elucidates both the epidemiological characteristics and molecular mechanisms of colorectal cancer. Our findings indicate that VEGFA, ICAM1, and IL6R play prominent roles in cancer progression. Proteomics analysis has identified multiple potential drug targets, and molecular docking and dynamic simulations have provided a theoretical foundation for developing drugs targeting VEGFA. Multi-omics studies have revealed that colorectal cancer progression involves intricate microbiome-host interactions, metabolic regulation, and immune response mechanisms, with factors such as Clostridia, 4E-BP1, AIFM1, and CXCL5 exhibiting dual roles. These discoveries not only deepen our understanding of colorectal cancer pathogenesis but also offer novel insights for optimizing diagnostic and therapeutic strategies, thereby laying the groundwork for developing personalized treatment regimens. Future research should focus on further validating these findings and exploring their potential clinical applications.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"954-972"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transforming beef quality through healthy breeding: a strategy to reduce carcinogenic compounds and enhance human health: a review. 通过健康养殖改变牛肉品质：减少致癌化合物和增进人类健康的策略：综述。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-09-01 Epub Date: 2025-05-09 DOI: 10.1007/s00335-025-10129-9

Belete Kuraz Abebe, Juntao Guo, Diba Dedacha Jilo, Jianfang Wang, Shengchen Yu, Haibing Liu, Gong Cheng, Linsen Zan

{"title":"Transforming beef quality through healthy breeding: a strategy to reduce carcinogenic compounds and enhance human health: a review.","authors":"Belete Kuraz Abebe, Juntao Guo, Diba Dedacha Jilo, Jianfang Wang, Shengchen Yu, Haibing Liu, Gong Cheng, Linsen Zan","doi":"10.1007/s00335-025-10129-9","DOIUrl":"10.1007/s00335-025-10129-9","url":null,"abstract":"The presence of carcinogenic substances in beef poses a significant risk to public health, with far-reaching implications for consumer safety and the meat production industry. Despite advancements in food safety measures, traditional breeding methods have proven inadequate in addressing these risks, revealing a substantial gap in knowledge. This review aims to fill this gap by evaluating the potential of healthy breeding techniques to significantly reduce the levels of carcinogenic compounds in beef. We focus on elucidating the molecular pathways that contribute to the formation of key carcinogens, such as heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs), while exploring the transformative capabilities of advanced genomic technologies. These technologies include genomic selection, CRISPR/Cas9, base editing, prime editing, and artificial intelligence-driven predictive models. Additionally, we examine multi-omics approaches to gain new insights into the genetic and environmental factors influencing carcinogen formation. Our findings suggest that healthy breeding strategies could markedly enhance meat quality, thereby offering a unique opportunity to improve public health outcomes. The integration of these innovative technologies into breeding programs not only provides a pathway to safer beef production but also fosters sustainable livestock management practices. The improvement of these strategies, along with careful consideration of ethical and regulatory challenges, will be crucial for their effective implementation and broader impact.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"787-811"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glycosylated protein-related microenvironmental features in breast cancer are associated with patient prognosis. 乳腺癌中糖基化蛋白相关微环境特征与患者预后相关。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-09-01 Epub Date: 2025-05-24 DOI: 10.1007/s00335-025-10137-9

Xiaoxiao Zhong, Jiaxuan Han, Huan Li, Xiangyu Shen, Bowen Yu, Ting Chen, Haobing Li, Jun Li, Jin Pang, Liyuan Qian, Wei Wu, Xiaoliang Tong, Boni Ding

{"title":"Glycosylated protein-related microenvironmental features in breast cancer are associated with patient prognosis.","authors":"Xiaoxiao Zhong, Jiaxuan Han, Huan Li, Xiangyu Shen, Bowen Yu, Ting Chen, Haobing Li, Jun Li, Jin Pang, Liyuan Qian, Wei Wu, Xiaoliang Tong, Boni Ding","doi":"10.1007/s00335-025-10137-9","DOIUrl":"10.1007/s00335-025-10137-9","url":null,"abstract":"The tumor microenvironment (TME) and aberrant glycosylation have been suggested to play key roles in cancer. This study integrated differentially expressed genes (DEGs) and weighted gene coexpression network analysis (WGCNA) to identify tumor microenvironment-related genes and construct a TME-risk prognostic signature (TMERS) through LASSO Cox regression. After batch effect removal, 44 TME-prognosis-related genes (TMEPGs) were identified and classified into three molecular subtypes via K-means clustering. The finalized 22-gene TMERS model demonstrated robust prognostic predictive capacity in GEO datasets. The results revealed distinct immune profiles and prognostic stratifications among genetic subtypes and risk groups, confirming that the TMERS is an independent prognostic indicator for breast cancer (BRCA). Glycosyltransferase genes (GTs) have potential therapeutic relevance through immune regulation, with TMEPG member killer cell lectin like receptor B1 (KLRB1) significantly correlated with BRCA prognosis. Cellular experiments demonstrated that KLRB1 overexpression suppressed BRCA cell proliferation and migration. This work establishes a novel prognostic model for BRCA while highlighting KLRB1 as a potential biomarker, providing new insights into TME-targeted therapeutic strategies.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"884-902"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of genomic breeding values and accuracy for carcass traits in Korean Hanwoo cows using whole-genome SNP chip panels. 利用全基因组SNP芯片评价韩国韩宇奶牛胴体性状的基因组育种价值和准确性。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-09-01 Epub Date: 2025-06-17 DOI: 10.1007/s00335-025-10142-y

Ji-Hee Jang, Han-Deul Lee, Jong-Joo Kim, Md Azizul Haque

{"title":"Evaluation of genomic breeding values and accuracy for carcass traits in Korean Hanwoo cows using whole-genome SNP chip panels.","authors":"Ji-Hee Jang, Han-Deul Lee, Jong-Joo Kim, Md Azizul Haque","doi":"10.1007/s00335-025-10142-y","DOIUrl":"10.1007/s00335-025-10142-y","url":null,"abstract":"Enhancing the quality and yield of Korean beef relies on improving carcass traits, including carcass weight (CWT), eye muscle area (EMA), backfat thickness (BF), and marbling score (MS). This study aimed to evaluate the accuracy of genomic EBVs for these traits using the genomic BLUP method. Phenotypic data were collected from 19,153 Hanwoo steers and 6,200 Hanwoo cows, with all animals genotyped using the Illumina Bovine 50K SNP chip. The population was divided into three groups to evaluate prediction accuracy. For CWT, theoretical accuracy reached 0.76, 0.75, and 0.78 for Groups 1, 2, and 3, respectively, with realized accuracy ranging from 0.70 to 0.74, indicating a strong correlation between predicted and actual performance. For EMA, theoretical accuracy ranged from 0.74 to 0.76, while realized accuracy was lower (0.64, 0.68, 0.69), suggesting the need for improved prediction models or larger, more diverse reference populations. BF showed theoretical accuracies of 0.75, 0.75, and 0.77, with realized accuracies of 0.59, 0.62, and 0.65. MS demonstrated the highest performance, with theoretical accuracies between 0.78 and 0.81, and realized accuracies between 0.73 and 0.78, reflecting a strong genetic component in marbling traits. This study underscores the importance of building a larger, cow-specific reference population to enhance GEBV prediction accuracy and maximize genetic gains in Hanwoo cow breeding programs.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"827-841"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of novel gene expression patterns and pathways involved in PARP-1 inhibitor resistance. PARP-1抑制剂耐药性的新基因表达模式和途径的鉴定。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-09-01 Epub Date: 2025-05-22 DOI: 10.1007/s00335-025-10134-y

Zulfa Khan, Anish Gomatam, Upadhyayula Suryanarayana Murty, Vaibhav A Dixit

{"title":"Identification of novel gene expression patterns and pathways involved in PARP-1 inhibitor resistance.","authors":"Zulfa Khan, Anish Gomatam, Upadhyayula Suryanarayana Murty, Vaibhav A Dixit","doi":"10.1007/s00335-025-10134-y","DOIUrl":"10.1007/s00335-025-10134-y","url":null,"abstract":"US-FDA has approved PARP-1 inhibitors (Talazoparib, Olaparib, Rucaparib, and Niraparib) as the first line of treatment for many cancer types (e.g., breast, ovarian, pancreatic, and prostate) caused by mutations in breast cancer gene 1 and 2 (BRCA1/2). However, developing resistance to PARP-1 inhibitors is a major concern, which limits therapeutic effectiveness. In the present study, we identified novel gene signatures implicated in developing resistance to Olaparib. Meta-analysis was performed on publicly available RNA-Seq data related to ovarian and breast cancers from the GEO (Gene Expression Omnibus) database. Differential gene expression analysis, gene ontology, KEGG pathway enrichment, and protein-protein interaction (PPI) networking analyses were performed. A total of 139 Common DEGs (Differentially Expressed Genes) were identified, comprising 69 and 70 genes that were upregulated and downregulated respectively. KEGG Pathways \"P53 signaling pathway\" and \"Positive regulation of developmental process(BP)\", \"endoplasmic reticulum lumen(CC),\" and \"growth factor binding(MF)\", were found to be potentially associated with Olaparib resistance. Five hub genes were identified using PPI networking of which FN1, CCN2, and JUN may play a significant role in the development of Olaparib resistance and could be promising therapeutic and diagnostic biomarkers for dealing with Olaparib resistance in BRCA1/2 mutant breast and ovarian cancer.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"872-883"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive identification of crucial biomarkers and therapeutic targets in cholestasis via integrated single-cell RNA and transcriptome sequencing analysis. 通过整合单细胞RNA和转录组测序分析，全面鉴定胆汁淤积症的关键生物标志物和治疗靶点。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2025-09-01 Epub Date: 2025-06-16 DOI: 10.1007/s00335-025-10146-8

Cichun Wu, Da Cheng, Juan Mo, Nianqi Zhou, Shifang Peng, Lei Fu

{"title":"Comprehensive identification of crucial biomarkers and therapeutic targets in cholestasis via integrated single-cell RNA and transcriptome sequencing analysis.","authors":"Cichun Wu, Da Cheng, Juan Mo, Nianqi Zhou, Shifang Peng, Lei Fu","doi":"10.1007/s00335-025-10146-8","DOIUrl":"10.1007/s00335-025-10146-8","url":null,"abstract":"Cholestasis, characterized by impaired bile flow, leads to significant hepatic dysfunction and poses a clinical challenge. This study investigated cellular communication networks and molecular mechanisms underlying cholestasis using advanced single-cell and transcriptomic sequencing. Data from the GEO database, including single-cell sequencing (GSE237622) and transcriptome datasets (GSE206364, GSE183754), were analyzed to identify biomarkers and therapeutic targets. Lasso regression highlighted IL32, CRIP2, ANXA2, and VWF as key genes, supported by immune infiltration, functional enrichment, and drug repurposing analysis via the Connectivity Map (CMap) database. Expression of these genes was validated in liver tissue from 13 cholestatic liver disease (CLD) patients and 10 controls. Single-cell sequencing identified 534 cell-type-specific markers, with significant upregulation of IL32, CRIP2, ANXA2, and VWF in CLD patients, particularly in endothelial cells near liver sinusoids and periportal areas. Their expression correlated with serum ALT and AST levels, reflecting disease severity. Drug repurposing analysis identified dexamethasone, fenofibrate, promazine, and SB-590,885 as potential therapies. This study identifies IL32, CRIP2, ANXA2, and VWF as pivotal biomarkers and therapeutic targets for cholestasis, offering new avenues for targeted interventions.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"928-938"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0