Functional & Integrative Genomics最新文献

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Identification of novel biomarkers and therapeutic targets for type II ketosis in dairy cows through metabolomics and snRNA-Seq 利用代谢组学和snRNA-Seq技术鉴定奶牛II型酮症的新生物标志物和治疗靶点
IF 3.1 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-01-02 DOI: 10.1007/s10142-025-01803-x
Xue Feng, Qi Feng, Shuang Liu, Lingkai Zhang, Sayed Haidar Abbas Raza, Bei Cai, Yanfen Ma, Fen Li, Yun Ma
{"title":"Identification of novel biomarkers and therapeutic targets for type II ketosis in dairy cows through metabolomics and snRNA-Seq","authors":"Xue Feng,&nbsp;Qi Feng,&nbsp;Shuang Liu,&nbsp;Lingkai Zhang,&nbsp;Sayed Haidar Abbas Raza,&nbsp;Bei Cai,&nbsp;Yanfen Ma,&nbsp;Fen Li,&nbsp;Yun Ma","doi":"10.1007/s10142-025-01803-x","DOIUrl":"10.1007/s10142-025-01803-x","url":null,"abstract":"<div><p>Type II ketosis in dairy cows is a common metabolic disorder characterized by hepatic lipid metabolism dysregulation. To investigate hepatic tissue heterogeneity and underlying molecular mechanisms in type II ketosis, this study utilized an integrated multi-omics and functional validation strategy. Serum (<i>n</i> = 20), plasma (<i>n</i> = 6), and liver tissue (<i>n</i> = 1 to 3) samples were obtained from Holstein cows in the early postpartum period (3 to 15 days), comparing ketotic and healthy groups. The experimental design combined plasma metabolomics (3 d postpartum, <i>n</i> = 6), cellular metabolomics (<i>n</i> = 6), single-nucleus RNA sequencing (snRNA-seq; 3 d postpartum, <i>n</i> = 1), bulk RNA-seq of hepatocytes (<i>n</i> = 6), and functional assays performed in primary bovine hepatocytes isolated from healthy donor livers (<i>n</i> = 3). This comprehensive framework enabled a systematic exploration of metabolic dysregulation, cellular diversity, and key disease-associated regulatory pathways. The study identified 15 potential biomarkers and extensive dysregulation of metabolic pathways. Liver tissues comprised 14 distinct cell types, with spatially heterogeneous hepatocyte subpopulations localized in periportal, midlobular, and central venous zones. Central venous hepatocytes were pivotal in lipid metabolism, whose reduction amplified interactions between hepatic stellate and endothelial cells, activating lipid-related pathways and driving disease progression. Critically, the ketone body-butyrate-HADHA axis was identified as a central pathogenic pathway. Silencing <i>HADHA</i> alleviated lipid metabolic dysfunction in hepatocytes induced by exogenous NEFA. Notably, <i>HADHA</i> exhibited dual regulatory roles in hepatic lipid metabolism under distinct pathological contexts. This study bridges hepatic cellular dynamics with systemic metabolic dysregulation, laying a theoretical foundation for mitigating lipid metabolism disorders in dairy cattle and informing translational applications in veterinary medicine.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145886865","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
ETS Homologous Factor (EHF) and Gamma Linolenic Acid (GLA): novel strategies for early diagnosis and treatment of endometriosis ETS同源因子(EHF)和γ -亚麻酸(GLA):早期诊断和治疗子宫内膜异位症的新策略
IF 3.1 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-01-02 DOI: 10.1007/s10142-025-01792-x
Mengjun Zhang, Jialin Wang, Haodi Yue, Zidi Zhang, Lindong Zhang, Xin Zhao
{"title":"ETS Homologous Factor (EHF) and Gamma Linolenic Acid (GLA): novel strategies for early diagnosis and treatment of endometriosis","authors":"Mengjun Zhang,&nbsp;Jialin Wang,&nbsp;Haodi Yue,&nbsp;Zidi Zhang,&nbsp;Lindong Zhang,&nbsp;Xin Zhao","doi":"10.1007/s10142-025-01792-x","DOIUrl":"10.1007/s10142-025-01792-x","url":null,"abstract":"<div>\u0000 \u0000 <p>Endometriosis (EMs) affects the physical and mental health of a wide range of women of childbearing age. Exploring specific diagnostic targets and screening potential therapeutic drugs will help early diagnosis and improve prognosis. The diagnostic and therapeutic potential of ETS homologous factor (EHF) and Gamma linolenic acid (GLA) remains to be explored. Based on RNA sequencing of GEO datasets and local clinical samples, LASSO and SVM-RFE machine learning algorithms were used to screen out the key gene (EHF). Explore the expression level of EHF and its effects on the malignant biological behavior and regulatory mechanism of endometriosis cells (12z). Based on the positive and negative correlation genes of EHF, cMap analysis and molecular docking were performed to screen out the potential therapeutic drug (GLA). Explore the therapeutic effects of GLA on endometriosis in vivo and in vitro. EHF was abnormally low in endometriosis tissues and cells. Overexpression of EHF could inhibit malignant phenotypes such as cell proliferation, migration, invasion, and angiogenesis, and inhibit the PI3K/AKT/mTOR axis, leading to cell cycle arrest and inhibiting epithelial-mesenchymal transition (EMT). GLA could play a potential therapeutic role in vivo and in vitro with low normal cell toxicity. EHF is a potential protective gene for endometriosis, and its overexpression could inhibit the malignant biological phenotype, cell cycle and EMT by inhibiting the PI3K/AKT/mTOR axis. GLA screened based on EHF could be used as a potential therapeutic drug to play a therapeutic role in vitro and in vivo. This study screened and validated specific diagnostic targets (EHF) and potential therapeutic drugs (GLA) for endometriosis based on clinical tissue sample tissue, cells, RNA sequencing, in vivo and in vitro experiments to assist in the early diagnosis and prognosis improvement of EMs.</p>\u0000 </div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145886866","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
Integrated genome-wide association study (GWAS) and metabolomics identify genetic and metabolic drivers of stripe rust resistance in wheat from the Western Himalayas 综合全基因组关联研究(GWAS)和代谢组学鉴定了西喜马拉雅地区小麦抗条锈病的遗传和代谢驱动因素
IF 3.1 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-01-02 DOI: 10.1007/s10142-025-01799-4
Farkhandah Jan, M. Parthiban, Sofora Jan, Anjan Kumar Pradhan, Sundeep Kumar, Safoora Shafi, Mahpara Bashir, Divya Sharma, Naeela Qureshi, Manish Kumar Vishwakarma, Sarabjit Kaur, Jaspal Kaur, Pradeep Kumar Bhati, Satinder Kaur, Mohd Anwar Khan, Rajeev Kumar Varshney, Reyazul Rouf Mir
{"title":"Integrated genome-wide association study (GWAS) and metabolomics identify genetic and metabolic drivers of stripe rust resistance in wheat from the Western Himalayas","authors":"Farkhandah Jan,&nbsp;M. Parthiban,&nbsp;Sofora Jan,&nbsp;Anjan Kumar Pradhan,&nbsp;Sundeep Kumar,&nbsp;Safoora Shafi,&nbsp;Mahpara Bashir,&nbsp;Divya Sharma,&nbsp;Naeela Qureshi,&nbsp;Manish Kumar Vishwakarma,&nbsp;Sarabjit Kaur,&nbsp;Jaspal Kaur,&nbsp;Pradeep Kumar Bhati,&nbsp;Satinder Kaur,&nbsp;Mohd Anwar Khan,&nbsp;Rajeev Kumar Varshney,&nbsp;Reyazul Rouf Mir","doi":"10.1007/s10142-025-01799-4","DOIUrl":"10.1007/s10142-025-01799-4","url":null,"abstract":"<div><p>Wheat production is increasingly threatened by biotic and abiotic stresses, with stripe rust, caused by <i>Puccinia striiformis</i> f. sp. <i>tritici</i> being among the most devastating diseases. To dissect stripe rust resistance mechanisms, 329 diverse wheat genotypes were evaluated across six distinct environments in India (three locations over two years). The panel exhibited wide variation for stripe rust resistance and was genotyped using a 35K SNP-array. Genome-wide association study (GWAS) revealed 49 significant marker–trait associations (MTAs), explaining 1.58% to 29.7% of phenotypic variation, with notable quantitative-trait locus (QTL) hotspots on chromosomes 2A, 3B and 4B. Several MTAs co-localized with known resistance loci, while <i>AX-92621629</i> appeared novel, suggesting new genomic region contributing to adult plant resistance. Candidate genes near significant single-nucleotide polymorphisms (SNPs) were enriched for defense-related functions, including nucleotide-binding site leucine-rich repeat (NBS-LRR) proteins, receptor-like kinases and transcription factors involved in defense signaling. To further investigate resistance mechanisms, metabolomic profiling, phytohormone and flavonoid dynamics were conducted on two contrasting wheat genotypes (resistant SKUA_415; susceptible SKUA_246) using untargeted Gas Chromatography–Mass Spectrometry (GC‒MS) and Liquid Chromatography–Mass Spectrometry (LC‒MS) approaches. Key defense-related metabolites, including myo-inositol, ketoglutaric acid, rutin and schaftoside and kaempferol derivatives were identified. These metabolites were downregulated in SKUA_246 following infection, while SKUA_415 showed up-regulation of defense phytohormones, anthocyanins and flavonoids. The two contrasting genotypes also exhibited clear allelic differentiation at key resistance-linked SNP loci, consistent with their divergent metabolomic responses. This study highlights identification of promising genes/QTLs/MTAs and metabolic markers for breeding next-generation stripe rust resistant wheat cultivars.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145886885","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
LEC2, a key player for cell totipotency in somatic embryogenesis and plant regeneration 在体细胞胚胎发生和植株再生过程中,细胞全能性起关键作用的LEC2
IF 3.1 4区 生物学
Functional & Integrative Genomics Pub Date : 2026-01-02 DOI: 10.1007/s10142-025-01801-z
Haifang Dai, Yueheng Lv, Zihao Liu, Lijie Li
{"title":"LEC2, a key player for cell totipotency in somatic embryogenesis and plant regeneration","authors":"Haifang Dai,&nbsp;Yueheng Lv,&nbsp;Zihao Liu,&nbsp;Lijie Li","doi":"10.1007/s10142-025-01801-z","DOIUrl":"10.1007/s10142-025-01801-z","url":null,"abstract":"<div>\u0000 \u0000 <p>Totipotency, the capacity of a single cell to regenerate a complete organism, is the central to plant developmental plasticity and underpins plant regeneration via somatic embryogenesis and/or organogenesis, a cornerstone of plant biotechnology, including transgenics and genome editing. A recent study, by using time-resolved single-cell and spatial transcriptomic analysis, Tang et al. 2025 shows that LEAFY COTYLEDON2 (LEC2) can reprogram a defined epidermal lineage, SPEECHLESS (SPCH)-expressing meristemoid mother cells (MMCs), into somatic embryo founder cells (SEFCs) by cooperating with SPCH to activate local auxin biosynthesis (TAA1/YUC4), producing a GMC-auxin transitional state that enables transcriptional and chromatin reconfiguration toward totipotency. This lineage-specific, auxin-driven route both refines conceptual models of plant reprogramming and offers practical levers to improve plant regeneration and transformation in crops.</p>\u0000 </div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145886864","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
Genome Editing Enhanced Abiotic Stress ToleranceIn Cereal Crops 基因组编辑增强谷类作物的非生物抗逆性
IF 3.1 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-12-26 DOI: 10.1007/s10142-025-01791-y
Shambhu Krishan Lal, Gullnaj Khatoon, Anurag Kumar, Krishan Kumar, Rakesh Kumar, Xiaoping Pan, Sudhir Kumar, Vijai Pal Bhadana, Avinash Pandey, Madan Kumar, Khela Ram Soren, Varakumar Panditi
{"title":"Genome Editing Enhanced Abiotic Stress ToleranceIn Cereal Crops","authors":"Shambhu Krishan Lal,&nbsp;Gullnaj Khatoon,&nbsp;Anurag Kumar,&nbsp;Krishan Kumar,&nbsp;Rakesh Kumar,&nbsp;Xiaoping Pan,&nbsp;Sudhir Kumar,&nbsp;Vijai Pal Bhadana,&nbsp;Avinash Pandey,&nbsp;Madan Kumar,&nbsp;Khela Ram Soren,&nbsp;Varakumar Panditi","doi":"10.1007/s10142-025-01791-y","DOIUrl":"10.1007/s10142-025-01791-y","url":null,"abstract":"<div><p>Cereals are crucial sources of food for human and animal populations worldwide. Their grain and fodder primarily serve as sources of energy and nutrition. Cereal production is hampered because of the prevalent abiotic stress worldwide. Abiotic stresses such as drought, salinity, extreme temperatures, and heavy metal toxicity significantly reduce global cereal crop production. Previously, traditional breeding and transgenic technology have been promising and potent approaches used to mitigate unfavourable abiotic stresses, enhancing crop production to some extent. The recent advent of more potent genome-editing technologies, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), has revolutionized the pace of crop improvement programs. Genome-editing technology using engineered nucleases offers significant opportunities for crop improvement. Genome editing tools include Meganucleases, Zinc Finger Nucleases (ZFN), Transcription activator-like effector nucleases (TALENs), and CRISPR/CRISPR-associated protein (Cas). Among all genome-editing tools, CRISPR/Cas9 has been widely used to improve crop cultivars due to its specificity, simplicity, robustness, and flexibility. Recent progress in genome-editing technology have improved various plant traits in cereals. Among these traits, cereal genotypes have shown substantial advances in the last decade, particularly in enhanced tolerance to abiotic stress, enabled by genome-editing tools. This review summarizes the recently developed cereal cultivars for abiotic stress tolerance that employ different genome-editing technologies, including the most recent additions, prime editing and base editing. These improved cereal cultivars perform better and maintain higher yields under adverse abiotic stresses.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831137","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
PCK1 attenuates intrahepatic cholangiocarcinoma progression by suppressing lactate accumulation and PI3K-AKT signaling PCK1通过抑制乳酸积累和PI3K-AKT信号传导减缓肝内胆管癌的进展
IF 3.1 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-12-26 DOI: 10.1007/s10142-025-01779-8
Yuchen Pei, Weigen Wu, Junlong Wang, Xi Yu, Borui Xu, Zhikang Li, Qianning Li, Xiting Chen, Danhong Zhan, Yao Li, Ruizhi Wang, Jiying Liu, Meifang He, Wei Chen
{"title":"PCK1 attenuates intrahepatic cholangiocarcinoma progression by suppressing lactate accumulation and PI3K-AKT signaling","authors":"Yuchen Pei,&nbsp;Weigen Wu,&nbsp;Junlong Wang,&nbsp;Xi Yu,&nbsp;Borui Xu,&nbsp;Zhikang Li,&nbsp;Qianning Li,&nbsp;Xiting Chen,&nbsp;Danhong Zhan,&nbsp;Yao Li,&nbsp;Ruizhi Wang,&nbsp;Jiying Liu,&nbsp;Meifang He,&nbsp;Wei Chen","doi":"10.1007/s10142-025-01779-8","DOIUrl":"10.1007/s10142-025-01779-8","url":null,"abstract":"<div><p>Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant liver cancer with limited treatment options. Recent evidence implicates lactate metabolism as playing a crucial role in tumor progression, but its precise contribution in iCCA remains unclear. In this study, lactate metabolism-related genes (LMRGs) in iCCA were identified through analyses of bulk and single-cell RNA sequencing data, diagnostic models were developed using machine learning algorithms, and the functional significance of candidate genes was validated through a combination of in <i>vitro</i> and in <i>vivo</i> experiments. 38 differentially expressed LMRGs were identified, and two genes, HMGCL and PCK1, were selected as robust diagnostic biomarkers. A nomogram incorporating both markers achieved excellent diagnostic performance (AUC = 0.999). Single-cell analyses revealed cell-type-specific expression and extensive intercellular communication involving these genes. Functional studies demonstrated that PCK1 acts as a tumor suppressor, concurrently reducing lactate accumulation, downregulating protein lactylation, and inhibiting the PI3K-AKT signaling pathway. Overexpressing PCK1 significantly impaired iCCA cell proliferation, migration, and invasion. These results indicate PCK1 is a key lactate metabolism-related tumor suppressor in iCCA. PCK1 exerts its anti-tumor effects by coordinately suppressing lactate accumulation and inhibiting the PI3K-AKT signaling pathway, positioning it as a promising diagnostic biomarker and therapeutic target for iCCA.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831529","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 the Nicotianamine synthase (NAS) gene family in wheat (Triticum aestivum L.) and the role of its member TaNAS4-A in Zn and Fe transport 小麦烟胺合成酶基因家族的鉴定及其成员TaNAS4-A在锌和铁转运中的作用
IF 3.1 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-12-23 DOI: 10.1007/s10142-025-01798-5
Gang Liu, Yixuan Sun, Pengyuan He, Yibo Wang, Yixuan Zhang, Qingfeng Li, Fenglou Liu, Shuangxi Zhang, Yingxia Zhang, Caixia Liu, Zhangjun Wang
{"title":"Identification of the Nicotianamine synthase (NAS) gene family in wheat (Triticum aestivum L.) and the role of its member TaNAS4-A in Zn and Fe transport","authors":"Gang Liu,&nbsp;Yixuan Sun,&nbsp;Pengyuan He,&nbsp;Yibo Wang,&nbsp;Yixuan Zhang,&nbsp;Qingfeng Li,&nbsp;Fenglou Liu,&nbsp;Shuangxi Zhang,&nbsp;Yingxia Zhang,&nbsp;Caixia Liu,&nbsp;Zhangjun Wang","doi":"10.1007/s10142-025-01798-5","DOIUrl":"10.1007/s10142-025-01798-5","url":null,"abstract":"<div><p>Zinc (Zn) and Iron (Fe) are essential trace elements for human health, yet deficiencies in both are widespread worldwide. As a major staple crop, wheat is an important dietary source of Zn and Fe. However, the concentrations of Zn and Fe in common wheat grains are generally low, making it necessary to enhance the nutritional value of wheat. This study first elaborated that both elements are absorbed by wheat via “Strategy II”, which relies on phytosiderophores (such as mugineic acids) and related transporter proteins (e.g., YSL and ZIP families). Nicotianamine (NA) plays a key chelating role in the long-distance transport of Zn and Fe. Therefore, we further analyzed the <i>NAS</i> gene family in wheat, which showed high genetic diversity, unique gene structures, distinct evolutionary features, and was subject to purifying selection. Expression profiling revealed that <i>NAS</i> genes were tissue-specific and responsive to various stress conditions. The overexpression of <i>TaNAS4-A</i> in rice, as well as the silencing of <i>TaNAS4-A</i> in wheat using BSMV-VIGS, confirmed the role of <i>TaNAS4-A</i> in enhancing NAS enzyme catalytic efficiency, promoting phytosiderophore secretion, and increasing the accumulation of Zn and Fe in grains. Additionally, this study suggested that <i>NAS</i> genes may confer other functions, such as stress resistance, which deserve further investigation. This research provides a theoretical basis for Zn and Fe biofortification in wheat.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808868","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
Integrating single-cell and bulk RNA-Seq to unravel the molecular mechanisms of airway stenosis 整合单细胞和大量RNA-Seq揭示气道狭窄的分子机制。
IF 3.1 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-12-23 DOI: 10.1007/s10142-025-01794-9
Cheng Xue, Wanyu Wang, Qihong Zhuang, Yihua Lin, Yiming Zeng
{"title":"Integrating single-cell and bulk RNA-Seq to unravel the molecular mechanisms of airway stenosis","authors":"Cheng Xue,&nbsp;Wanyu Wang,&nbsp;Qihong Zhuang,&nbsp;Yihua Lin,&nbsp;Yiming Zeng","doi":"10.1007/s10142-025-01794-9","DOIUrl":"10.1007/s10142-025-01794-9","url":null,"abstract":"<div><p>Central airway stenosis, arising from both benign and malignant etiologies, remains challenging to treat effectively. Elucidating the underlying molecular mechanisms is therefore essential. We integrated single-cell RNA sequencing with bulk transcriptomic data to identify key mechanisms in airway stenosis. Findings were subsequently validated using molecular biology assays. Fibroblasts were identified as key contributors to fibrotic remodeling in stenotic airways. Four genes—FAM118A, RCN3, PCSK7, and REEP3—were found to promote airway stenosis. Elevated immune activity was observed in stenotic tissues and showed a positive correlation with the expression of these genes. Mechanistically, these genes facilitate stenosis by activating KRAS→PI3K-AKT pathway, leading to upregulation of fibroblast activation markers. The expression of these genes is transcriptionally regulated by TBX20. Specifically, the ILF3-AS1/miR-212-5p axis regulates FAM118A, PCSK7, and REEP3, but not RCN3. This study aims to provide insights into the pathological mechanisms underlying airway stenosis, with all findings experimentally validated through integrated molecular and cellular approaches.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808807","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
Genome-wide identification of peroxidase genes and functional analysis of MtPRX76 on lignin synthesis in Medicago truncatula 苜蓿过氧化物酶基因的全基因组鉴定及MtPRX76在木质素合成中的功能分析。
IF 3.1 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-12-22 DOI: 10.1007/s10142-025-01781-0
Liu Bai, Lina Zhao, Yuanyuan Cui, Fengling Shi, Zhanmin Sun
{"title":"Genome-wide identification of peroxidase genes and functional analysis of MtPRX76 on lignin synthesis in Medicago truncatula","authors":"Liu Bai,&nbsp;Lina Zhao,&nbsp;Yuanyuan Cui,&nbsp;Fengling Shi,&nbsp;Zhanmin Sun","doi":"10.1007/s10142-025-01781-0","DOIUrl":"10.1007/s10142-025-01781-0","url":null,"abstract":"<div><p>Peroxidases (PRXs) are involved in diverse physiological processes, including cell elongation and lignification. However, studies on <i>PRX</i> genes and their tissue specificity in <i>Medicago truncatula</i> remain limited. In this study, 117 <i>MtPRX</i> genes were identified through bioinformatic analysis and classified into five distinct groups. Segmental duplications were identified as the major driving force for <i>MtPRX</i> expansion. Evolutionary analysis revealed closer phylogenetic relationships between <i>MtPRX</i> and <i>GmPR</i>X in soybean. Expression of <i>MtPRXs</i> were detected in roots, stems, leaves, flowers, seeds, and leaf buds, with members exhibiting distinct tissue-specific expression patterns. <i>Tnt1</i> insertion mutants of the tissue-specific gene <i>MtPRX76</i>, designated <i>mtprx76-1</i> and <i>mtprx76-2</i>, showed significantly reduced gene expression levels and decreased lignin content. Transcriptome analysis identified 3015 and 3564 differentially expressed genes (DEGs) in <i>mtprx76-1</i> and <i>mtprx76-2</i>, respectively. GO and KEGG enrichment analyses revealed that the phenylpropanoid biosynthesis pathway was the most significantly enriched. Furthermore, transcriptional levels of 14 key regulatory genes involved in lignin biosynthesis were significantly downregulated in both mutant lines. These results demonstrate that <i>MtPRX76</i> functions as a positive regulator influencing lignin biosynthesis. This study systematically characterizes the member features, sequence structures, evolutionary relationships, and tissue-specific expression patterns of the <i>MtPRX</i> gene family, and tissue specific expression patterns, while functionally validating <i>MtPRX76</i>. These findings establish a theoretical basis for understanding Class III <i>PRX</i> gene functions and breeding low lignin germplasm in alfalfa.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802809","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
Genome-wide characterization of WRKYs and identification of SpWRKY40 and SpWRKY51 as transcription activators in Sesuvium portulacastrum 猪叶Sesuvium portulacastrum转录激活因子的全基因组鉴定及SpWRKY40和SpWRKY51的鉴定
IF 3.1 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-12-22 DOI: 10.1007/s10142-025-01769-w
Yaoxiu Li, Fengyan Fang, Xiaoyou Wu, Tongjing Cui, Yingyi Yu, Zhaozhen Xiang, Guomei Zhang, Zhuangzhuang Nan, Shugang Hui
{"title":"Genome-wide characterization of WRKYs and identification of SpWRKY40 and SpWRKY51 as transcription activators in Sesuvium portulacastrum","authors":"Yaoxiu Li,&nbsp;Fengyan Fang,&nbsp;Xiaoyou Wu,&nbsp;Tongjing Cui,&nbsp;Yingyi Yu,&nbsp;Zhaozhen Xiang,&nbsp;Guomei Zhang,&nbsp;Zhuangzhuang Nan,&nbsp;Shugang Hui","doi":"10.1007/s10142-025-01769-w","DOIUrl":"10.1007/s10142-025-01769-w","url":null,"abstract":"<div><p>WRKYs represent a large family of plant transcription factors characterized by a highly conserved WRKY domain. WRKY transcription factors are important for plant growth, development, and responses to environmental stresses. However, this family has not been previously identified in <i>Sesuvium portulacastrum</i>, a typical halophyte that grows in saline soils and coastal marshlands and contributes to the stability of coastal ecosystems. Here, we identified 68 <i>SpWRKYs</i> from <i>S. portulacastrum</i> and classified them into six subclades. These genes were unevenly distributed across twenty-two chromosomes and exhibited both intra- and interspecific expansion based on segmental duplication events, orthologous gene pairs, and duplication relationships. All <i>SpWRKY</i> proteins contained at least one conserved WRKY domain, and their promoters contain 33 <i>cis</i>-elements involving abiotic stress signaling, developmental regulation, phytohormone responses, light responsiveness, and tissue-specific expression. Transcriptome analysis under cadmium, copper, and salt stress showed that many <i>SpWRKYs</i> were stress-responsive. Among them, <i>SpWRKY40</i> and <i>SpWRKY51</i> showed 3.8-fold and 4.2-fold induction in roots under cadmium treatment, which was further confirmed by quantitative real-time PCR. Subcellular localization and transient expression in tobacco, together with yeast one-hybrid experiments, demonstrated that SpWRKY40 and SpWRKY51 function as transcription activators. They bind specifically to the GTCAA and TTGACC <i>cis</i>-elements. Our study provides a detailed overview of the <i>SpWRKY</i> family and functional insights into SpWRKY40 and SpWRKY51 as transcription activators. The findings offer valuable candidate genes for future applications in improving cadmium stress tolerance in <i>S. portulacastrum</i> and related crop species.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802761","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}
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