Functional & Integrative Genomics最新文献

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Associations of host gene expression in the brain, liver, muscle with fecal and cecal microbiota composition in pigs 猪脑、肝、肌肉中宿主基因表达与粪便和盲肠微生物群组成的关系
IF 4 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-08-15 DOI: 10.1007/s10142-026-02009-5
Camila Sabino de Oliveira, Bárbara Silva-Vignato, Simara Larissa Fanalli, Mariah Castro Durval, Felipe André Oliveira Freitas, Andrezza Maria Felício, Lucas Echevarria Nascimento, Fernanda Nery Ciconello, Thiago Sugizaki dos Santos, Luciana Correia de Almeida Regitano, Luiz F. Brito, Aline Silva Mello Cesar
{"title":"Associations of host gene expression in the brain, liver, muscle with fecal and cecal microbiota composition in pigs","authors":"Camila Sabino de Oliveira,&nbsp;Bárbara Silva-Vignato,&nbsp;Simara Larissa Fanalli,&nbsp;Mariah Castro Durval,&nbsp;Felipe André Oliveira Freitas,&nbsp;Andrezza Maria Felício,&nbsp;Lucas Echevarria Nascimento,&nbsp;Fernanda Nery Ciconello,&nbsp;Thiago Sugizaki dos Santos,&nbsp;Luciana Correia de Almeida Regitano,&nbsp;Luiz F. Brito,&nbsp;Aline Silva Mello Cesar","doi":"10.1007/s10142-026-02009-5","DOIUrl":"10.1007/s10142-026-02009-5","url":null,"abstract":"<div><p>Understanding the genetic regulation underlying host–microbiota interactions is key to elucidating how microbial communities influence host metabolism, immunity, and physiology. In this context, the main objective of this study was to integrate genomic, transcriptomic, and microbial data to identify shared regulatory variants, highlight key microbial taxa, and prioritize biological pathways related to lipid metabolism, immune function, and host metabolic adaptation across multiple tissues in 72 immunocastrated male Large White pigs (S<i>us scrofa</i>). Expression quantitative trait <i>loci</i> (eQTL)-informed association analyses were performed to link the gut microbiota with host genetics. The analyses included microbial amplicon sequence variants (ASVs, ≥ 10% prevalence) from 16S rRNA sequencing, along with host cis- and trans-eQTL identified in brain, liver, and muscle tissues. Cross-tissue associations were detected between host gene expression and several bacterial genera, particularly <i>Oscillospira</i>, <i>Candidatus Methanoplasma</i>, <i>Roseburia</i>, <i>Anaerostipes</i>, and <i>Monoglobus</i>. A subset of eQTL, cis- and/or trans, showed multiple significant associations and regulated the expression of genes including <i>ZDHHC2</i>, <i>TMEM69</i>, and <i>CCDC167</i>, which have been implicated in lipid metabolism, immune regulation, and energy balance. The brain’s gene expression showed the most significant number of regulatory variants and enriched pathways related to fatty acid metabolism and immune processes, highlighting potential interactions along the gut–brain axis. These findings provide insights into the underlying host–microbiota relationships in pigs. Integrating eQTL and microbiota data across tissues revealed genetically mediated, cross-tissue regulatory networks linking microbial composition to host metabolic and immune functions. This offers a framework for functional validation and multi-omics studies in pigs.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-026-02009-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148752233","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
Integrated profiling identifies NCOA3 as a prognostic factor in patients with glioma 综合分析确定NCOA3是胶质瘤患者的预后因素。
IF 4 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-08-13 DOI: 10.1007/s10142-026-02007-7
Qian Luo, Jiaying Yang, Hailin Yin, Mei Yang, Yueyang Liang, Yixuan Hou, Xinze Sun, Jixuan Liu, Ling Zhang
{"title":"Integrated profiling identifies NCOA3 as a prognostic factor in patients with glioma","authors":"Qian Luo,&nbsp;Jiaying Yang,&nbsp;Hailin Yin,&nbsp;Mei Yang,&nbsp;Yueyang Liang,&nbsp;Yixuan Hou,&nbsp;Xinze Sun,&nbsp;Jixuan Liu,&nbsp;Ling Zhang","doi":"10.1007/s10142-026-02007-7","DOIUrl":"10.1007/s10142-026-02007-7","url":null,"abstract":"<div><p>Nuclear receptor coactivator 3 (NCOA3) is associated with various cancers, but its function and mechanism in glioblastoma multiforme (GBM) are still unclear. Bioinformatics analysis, in vitro cell experiments (NCOA3 silencing (si-NCOA3) or NCOA3 small-molecule inhibitor SI-2), in vivo animal models, and metabolic level detection were used to elucidate the activity of NCOA3 in GBM. The data revealed that GBM tissues had NCOA3 overexpression, which was linked with poor prognosis. It regulates pathways related to glycolysis, the cell cycle, and immunosuppression. Functionally, si-NCOA3/SI-2 suppressed GBM cell proliferation and migration. In vivo, sh-NCOA3/SI-2 demonstrated anti-glioma effects. Metabolically, treatment with si-NCOA3/SI-2 reduced glucose uptake, pyruvate and lactate production, ATP levels, and glycolysis-related enzyme expression in GBM cells. Combination therapy with SI-2 and TMZ enhanced GBM cell sensitivity to TMZ. Single-cell RNA sequencing revealed high NCOA3 expression in glioma stem cells (GSCs). si-NCOA3 inhibited GSCs proliferation and self-renewal while reducing the expression of Nestin and SOX2. NCOA3 is an oncogene in GBM. In mechanism, NCOA3 promotes GBM progression by enhancing the Warburg effect. In addition, NCOA3 is also highly expressed in GSCs and significantly promotes their proliferation and self-renewal ability. NCOA3 may represent a promising therapeutic target for GBM.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719921","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
Integrative multi-omics analysis identifies SMIM24 as a favorable prognostic biomarker in clear cell renal cell carcinoma 综合多组学分析发现SMIM24是透明细胞肾细胞癌的一个有利的预后生物标志物。
IF 4 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-08-13 DOI: 10.1007/s10142-026-02008-6
Zongyu Li, Yiting Liu, Yaxin Hou, Yuhong Ding, Zhenghao Liu, Yang Li, Pengjie Shi, Yixian Li, Yingchun Kuang, Lijie Zhou, Ke Chen, Lilong Liu
{"title":"Integrative multi-omics analysis identifies SMIM24 as a favorable prognostic biomarker in clear cell renal cell carcinoma","authors":"Zongyu Li,&nbsp;Yiting Liu,&nbsp;Yaxin Hou,&nbsp;Yuhong Ding,&nbsp;Zhenghao Liu,&nbsp;Yang Li,&nbsp;Pengjie Shi,&nbsp;Yixian Li,&nbsp;Yingchun Kuang,&nbsp;Lijie Zhou,&nbsp;Ke Chen,&nbsp;Lilong Liu","doi":"10.1007/s10142-026-02008-6","DOIUrl":"10.1007/s10142-026-02008-6","url":null,"abstract":"<div><p>Clear cell renal cell carcinoma (ccRCC) exhibits substantial molecular and clinical heterogeneity, contributing to variable disease progression and therapeutic outcomes. We previously identified a de-clear cell differentiation (DCCD) tumor state characterized by loss of canonical clear-cell features and aggressive clinical behavior. This study aimed to translate DCCD-associated biology into a prognostic framework and investigate its underlying molecular basis. Using TCGA-KIRC as the training cohort, we developed a five-gene prognostic signature comprising COL7A1, IGFN1, AJAP1, SMIM24, and ADGRV1, which consistently stratified patient survival across multiple public and institutional cohorts. Comparison with SSIGN, Leibovich, and ClearCode34-like models demonstrated that the DCCD signature provided complementary prognostic information. High-risk tumors exhibited enhanced proliferative and invasive programs, increased IL6-JAK-STAT3 pathway activity, and an immune-excluded microenvironment. Associations with treatment response were also observed in retrospective therapeutic cohorts. Integrated analyses of bulk and single-cell transcriptomics, spatial transcriptomics, tissue microarrays, CPTAC proteomics, and molecular interaction networks identified SMIM24 as an epithelial-associated factor linked to favorable outcomes and preserved metabolic programs. Functional experiments showed that SMIM24 overexpression suppressed migration, invasion, three-dimensional spheroid invasion, and clonogenic growth in ccRCC cells, accompanied by reduced JAK1 and STAT3 phosphorylation and decreased PD-L1 expression. Pharmacological activation of STAT3 with Colivelin partially restored PD-L1 expression in SMIM24-overexpressing cells. Collectively, these findings support the reproducibility of the DCCD-associated prognostic framework and identify SMIM24 as a candidate suppressor of ccRCC aggressiveness and PD-L1 expression, potentially acting in part through reduced STAT3 activation.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-026-02008-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719533","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
Genomic exploration of Serratia rubidaea MJ24 uncovers diverse biosynthetic capacity and agricultural relevance 红宝石沙雷氏菌MJ24的基因组研究揭示了其多样化的生物合成能力和农业相关性。
IF 4 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-08-12 DOI: 10.1007/s10142-026-02010-y
Yaseera N. Bhombal, Surabhi B. Yeole, Vitthal T. Barvkar, Anupama A. Pable
{"title":"Genomic exploration of Serratia rubidaea MJ24 uncovers diverse biosynthetic capacity and agricultural relevance","authors":"Yaseera N. Bhombal,&nbsp;Surabhi B. Yeole,&nbsp;Vitthal T. Barvkar,&nbsp;Anupama A. Pable","doi":"10.1007/s10142-026-02010-y","DOIUrl":"10.1007/s10142-026-02010-y","url":null,"abstract":"<div><p>The genus <i>Serratia</i> encompasses metabolically versatile and ecologically significant bacteria, yet the genomic and biosynthetic potential of <i>Serratia rubidaea</i> remains largely unexplored compared to the well-studied <i>S. marcescens</i>. In this study, we present a comprehensive genomic characterization of <i>S. rubidaea</i> MJ24, a pigment-producing strain isolated from the Western Ghats, India. The 4.98 Mb genome (GC content: 59.22%) assembled into 25 contigs exhibits 100% completeness and minimal contamination, indicating high assembly quality. Functional annotation revealed 4,692 (4,569 Protein coding) coding sequences enriched in metabolism-related genes, stress tolerance, and secondary metabolite biosynthesis. Genome mining using AntiSMASH identified twelve biosynthetic gene clusters (BGCs), including those responsible for prodigiosin, pyrrolnitrin, aerobactin, and enterobactin biosynthesis, which were experimentally confirmed by LC-QTOF-MS, along with two of moderate similarity and six other BGCs of unassigned function. Phylogenomic and ANI analyses confirmed its placement within the <i>S. rubidaea</i> clade. The strain harbors an array of plant growth-promoting traits, including phytohormone biosynthesis (IAA, cytokinins), siderophore production, stress control, and heavy metal resistance genes. Together, the BGCs and plant growth-promoting traits underscore its potential as a biocontrol agent and biofertilizer. Collectively, the findings reveal <i>S. rubidaea</i> MJ24 as a metabolically versatile bacterium with a rich secondary metabolite repertoire and significant agricultural and biotechnological promise.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719801","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
Integrative transcriptomic analysis and experimental validation identify GPR97 and PROK2 as novel genes upregulated in acute myocardial infarction 综合转录组学分析和实验验证证实GPR97和PROK2是急性心肌梗死中上调的新基因。
IF 4 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-08-10 DOI: 10.1007/s10142-026-02006-8
Yumin Meng, Qifan Chen, Jie Liu
{"title":"Integrative transcriptomic analysis and experimental validation identify GPR97 and PROK2 as novel genes upregulated in acute myocardial infarction","authors":"Yumin Meng,&nbsp;Qifan Chen,&nbsp;Jie Liu","doi":"10.1007/s10142-026-02006-8","DOIUrl":"10.1007/s10142-026-02006-8","url":null,"abstract":"<div><p>Acute myocardial infarction (AMI) is a major global health burden. Current diagnostic reliance on high-sensitivity cardiac troponin (hs-cTn) is limited by its lack of disease specificity and inability to reveal upstream molecular and immune mechanisms. This study aimed to identify robust core genes and their functional networks in AMI via integrated multi-dataset analysis and experimental validation. Three peripheral blood transcriptomic datasets (GSE60993, GSE61144, GSE97320) were obtained from GEO. Differentially expressed genes (DEGs) were identified using limma, with common DEGs extracted. Diagnostic performance was evaluated via ROC curves. Functional annotation used GO, KEGG and GSEA. Immune infiltration was analyzed with CIBERSORT. Key genes were validated in H9C2 cells under oxygen-glucose deprivation (OGD) using RT-qPCR and Western blot. Eight core genes were consistently upregulated in AMI peripheral blood, all showing high diagnostic accuracy (AUC &gt; 0.80). They were enriched in immune-inflammatory pathways. GSEA identified three activated pathways: adipocytokine signaling, leukocyte transendothelial migration and insulin signaling, with ACSL1, MMP9 and PYGL as key drivers. Immune analysis revealed increased neutrophils and decreased γδ T cells, with all eight genes positively correlating with neutrophil infiltration. The OGD model in H9C2 cells confirmed specific upregulation of GPR97, PROK2, ALPL and PADI4. This integrated computational and experimental study identifies a set of high-value diagnostic core genes in AMI. It first validates the specific upregulation of novel genes (GPR97, PROK2) in myocardial ischemia, placing them within a pathological network involving metabolic, immune and protective pathways. These findings provide new molecular insights and a foundation for novel diagnostics and therapeutic targets.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-026-02006-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700407","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
A pan-cancer analysis reveals the multifaceted role of PABPC1L in immune regulation and therapy response 泛癌症分析揭示了PABPC1L在免疫调节和治疗反应中的多方面作用。
IF 4 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-08-08 DOI: 10.1007/s10142-026-02004-w
Kangyue Sun, Peiyi He, Lu Chen, Bonian Mu, Kai Luo, Jianqun Cai, Aimin Li, Side Liu, Yue Zhang
{"title":"A pan-cancer analysis reveals the multifaceted role of PABPC1L in immune regulation and therapy response","authors":"Kangyue Sun,&nbsp;Peiyi He,&nbsp;Lu Chen,&nbsp;Bonian Mu,&nbsp;Kai Luo,&nbsp;Jianqun Cai,&nbsp;Aimin Li,&nbsp;Side Liu,&nbsp;Yue Zhang","doi":"10.1007/s10142-026-02004-w","DOIUrl":"10.1007/s10142-026-02004-w","url":null,"abstract":"<div><p>Although Poly(A)-binding protein cytoplasmic 1 like (PABPC1L) has been studied in specific cancer types, its broader potential as a prognostic biomarker remains uninvestigated, and the systematic pan-cancer analysis is currently lacking. We performed an integrated pan-cancer analysis of PABPC1L expression and function in 33 human malignant tumors. Associations between PABPC1L expression and tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironment composition, drug sensitivity, and response to immune checkpoint blockade (ICB) were also evaluated. A gastric cancer (GC) single-cell RNA sequencing dataset was analyzed to examine the correlation between PABPC1L expression and intercellular communication networks. The relationship between PABPC1L and PD-L1 expression was investigated in human colorectal cancer (CRC) tissue. Functional validation experiments were performed in CRC and GC cell lines. PABPC1L expression was consistently upregulated in multiple cancer types and significantly associated with poor patient prognosis. Notably, PABPC1L was identified as an immunomodulatory factor. It influenced the expression of multiple immune-related genes, regulates immune cell infiltration, and correlates with the outcomes following ICB therapy. Single-cell RNA sequencing analysis of GC further indicated that PABPC1L was involved in intercellular communication networks, including immune cells. In CRC, elevated PABPC1L expression was observed in tumor tissues and positively correlated with PD-L1 levels. Functional experiments confirmed that PABPC1L promoted cell proliferation, regulated cell cycle, and impaired the sensitivity of gastric and colorectal cells to 5-FU. In conclusion, PABPC1L is identified as exhibiting oncogenic properties and is proposed to function as a key regulator of tumorigenesis and immunotherapy resistance.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148696961","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
Precise dual-gene knockout of MSTN and SOCS2 via cytidine base editing enhances muscling and growth in goats 通过胞苷碱基编辑精确敲除MSTN和SOCS2双基因,可促进山羊的肌肉和生长。
IF 4 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-08-07 DOI: 10.1007/s10142-026-02002-y
Ling Li, Ming-Xing Cao, Muhammad Farhab, Paing Oo Kyaw, Shu-Qi Zhao, Yi Zhao, Feng-Lei Chen, Tariq Sohail, Ejaz Ahmad, Shao-Xian Cao, Yu-Guo Yuan
{"title":"Precise dual-gene knockout of MSTN and SOCS2 via cytidine base editing enhances muscling and growth in goats","authors":"Ling Li,&nbsp;Ming-Xing Cao,&nbsp;Muhammad Farhab,&nbsp;Paing Oo Kyaw,&nbsp;Shu-Qi Zhao,&nbsp;Yi Zhao,&nbsp;Feng-Lei Chen,&nbsp;Tariq Sohail,&nbsp;Ejaz Ahmad,&nbsp;Shao-Xian Cao,&nbsp;Yu-Guo Yuan","doi":"10.1007/s10142-026-02002-y","DOIUrl":"10.1007/s10142-026-02002-y","url":null,"abstract":"<div><h3>Background</h3><p>Myostatin (<i>MSTN</i>) and Suppressor of Cytokine Signaling 2 (<i>SOCS2</i>) are key negative regulators of muscle growth and development. Cytidine base editors (CBEs) offer a precise method for introducing stop codons to knock out these genes. This study aimed to apply the YE1-AncBE4max CBE system to edit <i>MSTN</i> and <i>SOCS2</i> in Haimen goats, a local Chinese breed, to enhance growth traits.</p><h3>Methods</h3><p>Efficient single guide RNAs (sgRNAs) targeting <i>MSTN</i> and <i>SOCS2</i> were screened in goat fetal fibroblasts via electroporation. Edited cells were analyzed by Sanger and TA-clone sequencing. Subsequently, a mixture of selected sgRNA and CBE mRNA was microinjected into 36 zygotes, which were then transferred to 9 recipient goats to generate gene-edited animals. Off-target effects were assessed by sequencing predicted sites.</p><h3>Results</h3><p>Cellular editing efficiencies for three <i>MSTN</i> sgRNAs were 25%, 37%, and 29%, and for one <i>SOCS2</i> sgRNA was 31.57%. Microinjection and embryo transfer resulted in the birth of five kids, and one fetus (#S91) was aborted at 3 months of gestation; four with dual-gene (<i>MSTN</i> &amp; <i>SOCS2</i>) edits (#241, #242, #S32, #S91) and two with single <i>SOCS2</i> edits (#S31, #S11). Notably, two dual-edited goats (#241, #242) harbored biallelic <i>MSTN</i> mutations. No off-target mutations were detected. Phenotypic analysis showed that the edited goats exhibited significantly increased body weight and a “double-muscling” phenotype by 90 days of age compared to wild-type controls. This is the first study of generating any species with double gene knock out (<i>MSTN</i>, and <i>SOCS2</i>) to date to the best of our knowledge.</p><h3>Conclusion</h3><p>This study successfully established a YE1-AncBE4max-based platform for efficient, precise dual-gene editing in goats. The generation of <i>MSTN/SOCS2</i>-edited Haimen goats with enhanced growth performance demonstrates the potential of base editing technology for rapid genetic improvement in livestock.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682715","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
Exosomal PKM2 from AML cells reprograms endothelial metabolism to promote angiogenesis and chemoresistance AML细胞外泌体PKM2重编程内皮代谢,促进血管生成和化疗耐药。
IF 4 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-08-06 DOI: 10.1007/s10142-026-02003-x
Xiaoting Wang, Ruolan You, Wenqi Fang, Lixia Kang, Danni Cai, Diyu Hou, Jingru Liu, Shuxia Zhang, Huifang Huang
{"title":"Exosomal PKM2 from AML cells reprograms endothelial metabolism to promote angiogenesis and chemoresistance","authors":"Xiaoting Wang,&nbsp;Ruolan You,&nbsp;Wenqi Fang,&nbsp;Lixia Kang,&nbsp;Danni Cai,&nbsp;Diyu Hou,&nbsp;Jingru Liu,&nbsp;Shuxia Zhang,&nbsp;Huifang Huang","doi":"10.1007/s10142-026-02003-x","DOIUrl":"10.1007/s10142-026-02003-x","url":null,"abstract":"<div><p>In acute myeloid leukemia (AML), therapeutic resistance is intimately linked to vascular microenvironment remodeling; however, the initiating molecular determinants remain elusive. Here, we identified exosomal pyruvate kinase M2 (PKM2) as a pivotal mediator of this pathogenic process. PKM2 was abundantly present in AML-derived exosomes and transferred to human umbilical vein endothelial cells (HUVECs), eliciting metabolic reprogramming characterized by enhanced glycolysis and angiogenic activation. Mechanistically, PKM2 knockdown in AML cells substantially attenuated exosome-induced endothelial migration and tube formation, whereas ectopic PKM2 overexpression in endothelial cells potentiated pro-angiogenic phenotypes. In NOD/SCID mouse xenograft, AML-derived exosomes promoted microvascular remodeling and accelerated disease progression, effects that were abrogated by the angiogenesis inhibitor endostatin. This vascular remodeling coincided with diminished cytarabine (Ara-C) sensitivity, indicative of a chemoprotective microenvironment. Consistently, in a systemic AML model, pharmacological PKM2 inhibition disrupted the vascular niche, suppressed angiogenesis, and restored Ara-C chemosensitivity. Clinically, PKM2 expression correlated positively with VEGFA and HIF-1α levels, and exosomes derived from AML patients with elevated PKM2 conferred enhanced tube-forming capacity upon endothelial cells. Collectively, these findings establish exosomal PKM2 as a critical regulator of the chemoprotective vascular niche in AML and underscore its translational potential as a therapeutic target.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676650","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
Whole genome sequencing and annotation of a non-pathogenic Fusarium brachygibbosum TZ1MST22 strain isolated from Medicago sativa in Southern Tunisian oases 突尼斯南部绿洲苜蓿非致病性短毛镰刀菌TZ1MST22的全基因组测序和注释
IF 4 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-08-05 DOI: 10.1007/s10142-026-02005-9
Amani Ben Alaya, Abdelmalek Lekired, Manel Chaouachi, Bilel Khiari, Imen Ben Slimene, Naceur Djébali
{"title":"Whole genome sequencing and annotation of a non-pathogenic Fusarium brachygibbosum TZ1MST22 strain isolated from Medicago sativa in Southern Tunisian oases","authors":"Amani Ben Alaya,&nbsp;Abdelmalek Lekired,&nbsp;Manel Chaouachi,&nbsp;Bilel Khiari,&nbsp;Imen Ben Slimene,&nbsp;Naceur Djébali","doi":"10.1007/s10142-026-02005-9","DOIUrl":"10.1007/s10142-026-02005-9","url":null,"abstract":"<div><p><i>Fusarium sambucinum</i> species complex (FSAMSC) includes not only major mycotoxin-producing pathogens but also non-pathogenic endophytic species that can promote plant growth and stress tolerance. However, the molecular mechanisms underlying these contrasting lifestyles remain poorly understood, underscoring the need for deeper molecular studies. A non-pathogenic endophytic <i>Fusarium</i> strain, TZ1MST22, isolated from <i>Medicago sativa</i> plants in the Tozeur region of Southern Tunisia, was sequenced using the Illumina NovaSeq 6000 sequencing technology. Here, we report a 39.8 Mb draft genome of TZ1MST22, comprising 160 contigs. Genome completeness was assessed using Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis, which yielded 99.4% completeness. Molecular phylogenetic analysis showed that TZ1MST22 was a <i>Fusarium brachygibbosum</i> belonging to <i>F. sambucinum</i> species complex (FSAMSC). In total, 12396 protein-coding genes were predicted. Of these, 769 genes were annotated as encoding CAZymes, including 46 cellulose-degrading, 62 hemicellulose-degrading, and 38, 25, 8, and 31 chitin/chitosan-, glucan-, lignin-, and pectin-degrading enzymes, respectively, as well as 74 sugar-, poly-, and oligosaccharide-degrading enzymes, and 61 others, including cutinases. In addition, 38 secondary metabolism gene clusters were identified, mainly including terpenes, T1 polyketide synthase genes, and non-ribosomal peptide synthase genes. Comparative genomic analyses revealed that <i>F. brachygibbosum</i> TZ1MST22 harbors more biomass-degrading enzymes than other pathogenic and endophytic <i>Fusarium</i> species. These results expand our genetic knowledge of <i>Fusarium brachygibbosum</i>, as this genome represents the third published genome of this species and the first non-pathogenic one. Our comprehensive whole-genome analysis provides a valuable resource for future studies on gene expression, regulation, function, evolution, and will support efforts to optimize its cultivation for the high-yield production of useful metabolites.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676628","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
IFI6 is associated with interferon activation and complement-associated immune responses in primary Sjögren’s disease IFI6与原发性Sjögren疾病中的干扰素激活和补体相关免疫反应相关。
IF 4 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-08-05 DOI: 10.1007/s10142-026-02000-0
Yibing Han, Yikun Mei, Xiaoqin Meng, Minjv Zhang, Shuo Yang, Weizhi Wang, Wen Qiu, Zuoqing Dong
{"title":"IFI6 is associated with interferon activation and complement-associated immune responses in primary Sjögren’s disease","authors":"Yibing Han,&nbsp;Yikun Mei,&nbsp;Xiaoqin Meng,&nbsp;Minjv Zhang,&nbsp;Shuo Yang,&nbsp;Weizhi Wang,&nbsp;Wen Qiu,&nbsp;Zuoqing Dong","doi":"10.1007/s10142-026-02000-0","DOIUrl":"10.1007/s10142-026-02000-0","url":null,"abstract":"<div><p>Primary Sjögren’s disease (pSjD) is a systemic autoimmune disease characterized by chronic immune-mediated inflammation of exocrine glands and a prominent type I interferon (IFN-I) signature. However, the molecular mechanisms linking interferon signaling with downstream immune and inflammatory pathways in pSjD remain incompletely understood. In this study, we performed an integrative analysis combining public transcriptomic datasets, immune infiltration analysis, single-cell RNA sequencing, and experimental validation to investigate the potential involvement of interferon alpha-inducible protein 6 (IFI6) in pSjD. Differential expression and network analyses identified IFI6 as an upregulated interferon-stimulated gene associated with immune-related pathways. Immune infiltration analysis showed that IFI6 expression was associated with activated dendritic cells and CD4⁺ memory T cells. Single-cell RNA sequencing further indicated preferential expression of IFI6 in dendritic cell subsets. Clinical validation revealed increased serum IFI6 levels in patients with pSjD, which were negatively associated with salivary flow rate. In addition, immunoprecipitation coupled with proteomic analysis identified complement-related proteins within IFI6-associated complexes, and enrichment analysis suggested the involvement of complement activation pathways. Overall, these findings indicate that IFI6 expression is associated with interferon-related immune activation and complement-associated inflammatory pathways in pSjD. IFI6 may serve as a potential biomarker reflecting interferon-related immune activation and is associated with reduced salivary flow rate in pSjD, although further studies are required to clarify its precise functional role.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672761","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
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