Functional & Integrative Genomics最新文献

{"title":"Integrative analysis identifies FERMT3 as a key regulator of metabolic reprogramming in keloid scarring and metabolic syndrome","authors":"Qian Lin,&nbsp;Beichen Cai,&nbsp;Feng Dong,&nbsp;Ruonan Ke,&nbsp;Xiuying Shan,&nbsp;Xuejun Ni,&nbsp;Lu Chen,&nbsp;Chuanshu Cai,&nbsp;Biao Wang","doi":"10.1007/s10142-025-01705-y","DOIUrl":"10.1007/s10142-025-01705-y","url":null,"abstract":"<div><p><i>Background</i>. Keloid scarring and Metabolic Syndrome (MS) are distinct conditions marked by chronic inflammation and tissue dysregulation, suggesting shared pathogenic mechanisms. Identifying common regulatory genes could unveil novel therapeutic targets. <i>Methods</i>. We performed an integrative analysis of public microarray datasets from keloid, MS, and respective healthy control tissues. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify shared gene modules. A diagnostic gene signature was developed using LASSO regression and machine learning, and validated on independent datasets. Single-cell RNA sequencing (scRNA-seq) data were analyzed to localize gene expression to specific cell types. The function of a top candidate gene, <i>FERMT3</i>, was investigated via in vitro experiments in macrophages and fibroblasts. <i>Results</i>. We identified 2,788 differentially expressed genes (DEGs) in keloids and 2,639 in MS compared to healthy controls, with 146 genes overlapping. WGCNA identified a key co-expression module (termed the “salmon” module) significantly associated with both conditions and enriched in metabolic and immune pathways. A 23-gene signature demonstrated fair to good predictive performance for both keloids (validation AUC = 0.783) and MS (AUC = 0.905). scRNA-seq analysis revealed that FERMT3 was highly expressed in macrophages and fibroblasts in keloid tissue. In vitro, modulation of FERMT3 in these cell types significantly altered their metabolic profiles (glycolysis, oxidative phosphorylation), inflammatory cytokine production, proliferation, and migration. <i>Conclusions</i>. Our integrative analysis identifies a shared transcriptomic signature between keloids and MS and highlights <i>FERMT3</i> as a key potential regulator of the metabolic and inflammatory phenotypes in these conditions. These findings suggest that <i>FERMT3</i> could be a promising therapeutic target for diseases driven by fibro-metabolic dysregulation.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021517","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}

{"title":"Genome-wide identification analysis of aldo–keto reductase gene family in cotton and GhAKR40 role in salt stress tolerance","authors":"Yiman Liu,&nbsp;Qiankun Liu,&nbsp;Yuqing Hou,&nbsp;Guangxing Zhang,&nbsp;Jiangping Han,&nbsp;Zhaoguo Li,&nbsp;Aziz Khan,&nbsp;Zhongli Zhou,&nbsp;Xiaoyan Cai,&nbsp;Yanchao Xu,&nbsp;Jie Zheng,&nbsp;Fang Liu","doi":"10.1007/s10142-025-01678-y","DOIUrl":"10.1007/s10142-025-01678-y","url":null,"abstract":"<div><p>In this study, a comprehensive genome-wide identification and analysis of the aldo–keto reductase (AKR) gene family was performed to explore the role of <i>Gossypium hirsutumAKR40</i> under salt stress in cotton. A total of 249 AKR genes were identified with uneven distribution on the chromosomes in four cotton species. The diversity and evolutionary relationship of the cotton AKR gene family was identified using physio-chemical analysis, phylogenetic tree construction, conserved motif analysis, chromosomal localization, prediction of cis-acting elements, and calculation of evolutionary selection pressure under 300 mM NaCl stress. The real-time qPCR showed that genes encoding members of the aldo–keto reductase (AKR) family in <i>Gossypium hirsutum</i> displayed distinct expression patterns various stress treatments. Specifically, the expression levels of certain genes were significantly upregulated under drought and salt stress. Notably, the role of <i>GhAKR40</i> gene in salt stress tolerance was validated using virus-induced gene silencing (VIGS) technology in cotton. The <i>GhAKR40</i>-silenced plants experienced leaf wilting under salt stress compared with wild-type and null-control plants. In addition, a series of physio-biochemical such as DAB staining and measurement of RWCL (relative water content in leaves) indexes also indicated that silencing of the <i>AKR40</i> gene reduced the salt tolerance in cotton. Transcriptome sequencing and analysis of the VIGS-silenced lines suggest that <i>GhAKR40</i> may enhance salt tolerance in cotton plants by potentially participating in plant-pathogen interactions and the MAPK signaling pathway, thereby modulating both pathways. These data demonstrate that <i>GhAKRs</i> play a significant role in salt stress tolerance. <i>GhAKR40</i> functions as a positive regulator with a significant impact on stress tolerance. This study not only establishes a theoretical foundation for the comprehensive utilization of resistant germplasm resources in cotton but also paves the way for further exploration of resistance genes in the species.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007840","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}

{"title":"CircSHPRH inhibits malignancy progression of head and neck squamous cell carcinoma by regulating PI3K/AKT/mTOR signaling pathway","authors":"Fei Zhang,&nbsp;Liu Chen,&nbsp;Chuanxin Duan,&nbsp;Yingnan Zhu","doi":"10.1007/s10142-025-01677-z","DOIUrl":"10.1007/s10142-025-01677-z","url":null,"abstract":"<div><h3>Background</h3><p>Head and neck squamous cell carcinoma (HNSCC) stands as a significant global health concern, marked by its substantial impact on both morbidity and mortality rates. Although previous studies have suggested that circular RNAs (circRNAs) may influence HNSCC progression, the underlying mechanisms remain largely unclear.</p><h3>Methods</h3><p>In this study, we first used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of circSHPRH in HNSCC tissues and cell lines. Subsequently, we assessed its impact on cell proliferation, migration, invasion, and apoptosis using CCK-8 assays, colony formation assays, wound healing assays, Transwell assays, and flow cytometry. Additionally, we investigated the molecular mechanisms by which circSHPRH exerts its effects, focusing on the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. In vivo experiments were conducted using a xenograft tumor model in nude mice to validate the tumor-suppressive effects of circSHPRH.</p><h3>Results</h3><p>Our results demonstrated a significant downregulation of circSHPRH in HNSCC tissues and cell lines compared to their normal counterparts. Overexpression of circSHPRH in HNSCC cells led to a marked reduction in cell proliferation, migration, and invasion, while promoting apoptosis. Mechanistically, we found circSHPRH exerts its tumor-suppressive effects by suppressing the PI3K/AKT/mTOR signaling pathway. This finding was corroborated by in vivo experiments in nude mice, where an upregulation of circSHPRH led to a reduction in tumor growth in HNSCC.</p><h3>Conclusion</h3><p>CircSHPRH may play a pivotal role in attenuating the growth and metastasis of HNSCC, both at the cellular level and in animal models, by disrupting the PI3K/AKT/mTOR signaling axis.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998578","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}

{"title":"CLDN4 promotes ferroptosis and inflammation involving JAK2/STAT3 pathway in acute pancreatitis","authors":"Chuanming Zheng,&nbsp;Rui Tao,&nbsp;Zhenjie Wang,&nbsp;Xi Zhang,&nbsp;Hai Jiang,&nbsp;Zhong Ji,&nbsp;Hehe Dou,&nbsp;Zhaohui Du","doi":"10.1007/s10142-025-01683-1","DOIUrl":"10.1007/s10142-025-01683-1","url":null,"abstract":"<div><p>Acute pancreatitis (AP) is a severe inflammatory disease characterized by pancreatic acinar cell injury and oxidative stress. Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, has been implicated in AP pathogenesis. However, the molecular mechanisms linking ferroptosis to AP remain unclear. Using a cerulein-induced AP mouse model and cerulein-stimulated 266-6 pancreatic acinar cells, we performed RNA sequencing to identify differentially expressed genes (DEGs). Claudin-4 (CLDN4) was selected for further investigation. We evaluated the effects of CLDN4 knockdown on cell viability, apoptosis, inflammatory cytokine production, ferroptosis markers, and janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway utilizing quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, enzyme-linked immunosorbent assays (ELISA), immunofluorescence, flow cytometry, and histopathological analyses, respectively. We found that CLDN4 expression was significantly upregulated in AP pancreatic tissues and cells. CLDN4 knockdown enhanced cell viability, reduced apoptosis, and decreased reactive oxygen species (ROS), iron accumulation, and inflammatory cytokines (TNF-α, IL-6, IL-17). It also restored glutathione peroxidase 4 (GPX4) levels and reduced acyl-CoA synthetase long-chain family member 4 (ACSL4) expression, indicating suppression of ferroptosis. In vivo, CLDN4 knockdown ameliorated pancreatic injury and oxidative stress. Mechanistically, CLDN4 knockdown correlated with decreased activation of the JAK2/STAT3 pathway, and combined inhibition with AG490 provided additive protective effects. Our study identifies CLDN4 as a novel regulator of ferroptosis and inflammation in AP that may be linked to the JAK2/STAT3 pathway. Targeting CLDN4 may offer a promising therapeutic strategy for mitigating pancreatic injury in acute pancreatitis.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927147","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}

{"title":"Genetic variants of LncRNA associated with splicing regulation and their impact on ovarian cancer development","authors":"Lingxiao Zou,&nbsp;Meng Zhang,&nbsp;Shan He,&nbsp;Minhui Zhuang,&nbsp;Wenjing Jia,&nbsp;Yulan Wang,&nbsp;Jingjing Liu,&nbsp;Yixuan Wang,&nbsp;Xiaofeng Song,&nbsp;Jian Zhao","doi":"10.1007/s10142-025-01687-x","DOIUrl":"10.1007/s10142-025-01687-x","url":null,"abstract":"<div><p>Ovarian cancer (OC) is a highly lethal gynecologic malignancy that lacks reliable early biomarkers. Numerous long non-coding RNAs (lncRNAs) have been found to play critical regulatory roles in OC, yet the mechanisms underlying most of them remain unclear. Recently, lncRNAs have emerged as key regulators of RNA splicing, while splicing dysregulation is widespread and plays critical roles in cancer. In addition, genetic variants of splicing regulators have been shown to contribute to disease etiology. In this study, we comprehensively analyzed 202 °C samples and characterized 21,129 lncRNA splicing quantitative trait loci (sQTLs) involving both event-level and transcript-level. We found that lncRNA sQTLs differ significantly from lncRNA expression quantitative trait loci (eQTLs), and genes regulated by lncRNA sQTLs are involved in cancer hallmark pathways and associated with immune cell infiltration and drug sensitivity. Additionally, these lncRNA sQTLs are significantly enriched in histone markers, transcription factor (TF) binding sites, and RNA-binding protein (RBP) binding sites, including several critical splicing factors (SF) in OC. Based on SF binding and partial correlation analysis, a potential lncRNA-SF-mRNA regulatory network was constructed. Finally, by integrating GWAS data, we elucidated that a specific lncRNA sQTL rs1549334 generates different isoforms by regulating the splicing of the HOXD3 gene and thus impacting OC risk. Our study provides new insights into the mechanisms of splicing regulation in OC involving lncRNA sQTL and reveals potential biomarkers for early detection and clinical treatment of OC.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927148","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}

{"title":"Protein networks: integrating pathways for plant heat stress adaptation","authors":"Akmal Zubair,&nbsp;Sania Zaib,&nbsp; Malaika,&nbsp; Karishma,&nbsp;Manal S. Ebaid","doi":"10.1007/s10142-025-01685-z","DOIUrl":"10.1007/s10142-025-01685-z","url":null,"abstract":"<div><p>Plants’ immobility renders them highly vulnerable to heat stress, which disrupts water relations, photosynthesis, respiration, and cellular homeostasis, ultimately reducing growth and yield. To survive, plants deploy a multifaceted heat stress response (HSR) that integrates calcium signaling, molecular chaperones, antioxidant enzymes, and phytohormonal networks. This review synthesizes recent advances in understanding the molecular crosstalk between phytohormones and protein synthesis during plant heat stress responses, with a particular focus on two key HSR modules: protein synthesis pathways, especially heat shock proteins (HSPs), and phytohormone signaling networks involving abscisic acid, cytokinins, ethylene, salicylic acid, and jasmonic acid. It also highlights the convergence of these pathways through calcium-dependent protein kinases (CDPKs) and reactive oxygen species (ROS) signaling. We present mechanistic insights into: (1) CDPK-mediated activation of heat shock transcription factors (HSFs) and hormone-responsive factors; (2) APX-driven ROS scavenging and its impact on crop thermotolerance; and (3) hormone-engineered strategies that enhance yield stability under high temperatures. By consolidating findings from recent meta-analyses and molecular studies, we identify critical nodes for biotechnological intervention, such as CDPK and APX overexpression, and propose field-oriented research priorities, including hormone-engineered crop trials and integrative breeding approaches. This forward-looking framework can help guide biotechnological interventions to enhance crop resilience and support the development of climate-smart crops aimed at safeguarding global food security in a warming world.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927149","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}

{"title":"MED12-STAT1-TAP2 axis regulates CD8 + T cell cytotoxicity and mediates immunotherapy outcome in non-small cell lung cancer","authors":"Minghao Feng,&nbsp;Yuxu Niu,&nbsp;Jiayuan Liu,&nbsp;Gang Liu","doi":"10.1007/s10142-025-01690-2","DOIUrl":"10.1007/s10142-025-01690-2","url":null,"abstract":"<div><p>Although immunotherapy for late-stage non-small cell lung carcinoma (NSCLC) has been clinically utilized, its prognosis remains highly heterogeneous, prompting us to investigate novel predictive immunotherapy biomarkers for NSCLC. We analyzed the correlations between MED12 nonsynonymous mutations and survival, clinical, genomic, transcriptomic information, and immune infiltration information through data mining across multiple datasets. We also investigated the mechanism of MED12 using luciferase assay, Western blot, ChIP-PCR, and siRNA. MED12 is significantly associated with survival in completely independent immunotherapy datasets, including MSKCC (<i>N</i> = 350), Naiyer2015 (<i>N</i> = 34), our own (<i>N</i> = 295) and the pan-cancer dataset, but not in the TCGA dataset, where patients received non-immunotherapy regimens. Mutations in MED12 showed no significant correlation with known metrics (TMB, IPS/CTLA4/PD1 status, PD-1/PD-L1 expression, and TCR/BCR status) or DNA Damage Repair (DDR) pathway mutations, yet they carried independent prognostic information according to the Cox multivariate regression. On the other hand, MED12 mutation is significantly associated with multiple immune-related pathways and immune infiltration of CD8 + T cells and activated NK cells. Lactate dehydrogenase assay revealed that knockdown of TAP2 restored the upregulation of CD8 + T cell cytotoxicity triggered by MED12 knockdown. ChIP-PCR, luciferase assay and siRNA knock down assay indicate that MED12 binds to the promoter region of STAT1 to suppress its transcription, while the transcription factor STAT1 promotes the transcription of TAP2, thus inhibiting the antigen processing and presentation. Collectively, MED12 mutation is an independent and valuable biomarker for predicting the response to immune checkpoint inhibitor (ICI)therapy in NSCLC by modulating CD8 + T cell cytotoxicity via the STAT1/TAP2 axis.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01690-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923100","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}

{"title":"Exploring potential associations and biomarkers linked polycystic ovarian syndrome with atherosclerosis via comprehensive bioinformatics analysis, machine learning, and animal experiments","authors":"Xiaoxuan Zhao,&nbsp;Yuanyuan Zhang,&nbsp;Qingnan Fan,&nbsp;Yuanfang He,&nbsp;Yiming Ma,&nbsp;Miao Sun,&nbsp;Yang Zhao,&nbsp;Yuepeng Jiang,&nbsp;Dan Jia","doi":"10.1007/s10142-025-01686-y","DOIUrl":"10.1007/s10142-025-01686-y","url":null,"abstract":"<div><p>Polycystic ovary syndrome (PCOS), a common endocrine condition affecting multiple systems, is tied to atherosclerosis (AS) progression among reproductive-aged women. The present study aimed to explore the underlying associations and uncover potential biological indicators for PCOS complicated with AS. Gene expression datasets for PCOS and AS were obtained from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) from PCOS tissues (granulosa cells, adipose tissue, skeletal muscle) and arterial wall of AS were analyzed via weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Immune infiltration and chemokine/receptor-immunocyte networks were constructed to explore immune cell recruitment. Key findings were validated in PCOS and AS murine models. The gradient boosting machine (GBM) and the extreme gradient boosting (XGBoost) algorithms were employed to identify potential biomarkers, further verified by the AS murine model, nomograms, and PCOS murine model. We identified 238, 60, and 76 secretory protein-encoding DEGs in PCOS tissues (granulosa cells, adipose tissue, and skeletal muscle) and 604 key AS-related DEGs. The enrichment analysis suggested associations between immune inflammation, dysregulated lipid metabolism, insulin signaling, and PCOS-related AS. Then, immunoinfiltration analysis revealed elevated naive B cell, follicular T helper cell, and neutrophil proportions in AS samples. In addition, six chemokines (CCL5, CCL20, CCL23, CCL28, CXCL1, and CXCL6) were involved in four immunocyte recruitments (B cells, neutrophils, NK cells, and CD4⁺ T cells) in AS, with CXCL1 and CXCL6 upregulated in the peripheral blood of PCOS mice. And CXCR2, the shared receptor for CXCL1/6, showed an increase in aortic tissues of both AS and PCOS mice. Machine learning identified five signature genes (LILRA5, CSF2RA, S100A8, CD6, and CCL24; AUC 0.856–0.983), two of which (CSF2RA and LILRA5) were verified in the AS murine model and the nomogram incorporating these genes showed strong predictive accuracy (AUC = 0.966). Finally, further validation in the PCOS murine model confirmed significantly elevated CSF2RA and reduced LILRA5 expression, suggesting a close association between PCOS and AS pathogenesis. This study identified potential associations between PCOS and AS, and screened the potential biological biomarkers for predicting PCOS-related AS, offering a foothold for future exploration of the diagnosis and risk stratification for PCOS-related AS.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918461","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}

{"title":"Validation of caprine H11 and the Rosa26 platform for transgene integration via CRISPR-based system: investigations on stable transgene expression and genetic biosafety","authors":"Yaoguang Zhang,&nbsp;Fei Hao,&nbsp;Yuan Gao,&nbsp;Weiguo Song,&nbsp;Chang Su,&nbsp;Xudong Guo,&nbsp;Dongjun Liu","doi":"10.1007/s10142-025-01679-x","DOIUrl":"10.1007/s10142-025-01679-x","url":null,"abstract":"<div><p>CRISPR/Cas9 technology is an efficient tool for site-specific livestock gene editing. However, to minimize potential disruption of host genome function, exogenous genes should be integrated into well-characterized genomic loci, such as <i>H11</i> or <i>Rosa26</i>, which have been empirically validated for stable transgene expression. This study established a multi-dimensional assessment system to evaluate the biological applicability of the <i>H11</i> locus and the widely used <i>Rosa26</i> targeting platform as sites for targeted integration of exogenous genes in goats. Donor cells carrying the enhanced green fluorescent protein (<i>EGFP</i>) reporter gene at the <i>H11</i> and <i>Rosa26</i> loci were generated via CRISPR/Cas9-mediated homology-directed repair; this was followed by somatic cell nuclear transfer to produce transgenic cloned embryos and healthy offspring. Multi-dimensional analyses revealed the following. At the cellular level, there was stable and efficient <i>EGFP</i> expression at integration sites, with donor cells maintaining normal cell cycle progression, proliferation capacity, and apoptosis levels, and with no alterations in the transcriptional integrity of adjacent genes. At the embryonic level, there was sustained <i>EGFP</i> expression across pre-implantation embryonic stages, with developmental metrics statistically indistinguishable from wild-type embryos. Finally, at the individual level, cloned offspring exhibited growth phenotypes consistent with wild-type counterparts, and <i>EGFP</i> showed broad-spectrum expression in eight tissues. This study establishes the first CRISPR/Cas9-based crossscale (cellular–embryonic–individual) validation in goats, demonstrating that the <i>H11</i> and <i>Rosa26</i> loci support efficient and stable transgene integration in goats. These results provide a precise and predictable technical framework for livestock genetic improvement.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01679-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914732","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}

{"title":"MBTPS1: a membrane-bound transcription factor protease implicated in the pathogenesis of several skin and skeletal disorders","authors":"Haisheng Huang,&nbsp;Yumeng Wang,&nbsp;Fuying Chen,&nbsp;Anqi Zhao,&nbsp;Wei He,&nbsp;Ming Li","doi":"10.1007/s10142-025-01694-y","DOIUrl":"10.1007/s10142-025-01694-y","url":null,"abstract":"<div><p>The <i>MBTPS1</i> gene, which is located on chromosome 16q24, encodes the membrane-bound transcription factor protease site-1 (MBTPS1), commonly referred to as site-1 protease (<i>S1P</i>). S1P can process a variety of substrates independently or in conjunction with membrane-bound transcription factor protease site-2 (MBTPS2, also known as S2P), including sterol regulatory element binding proteins (SREBPs), activating transcription factor 6 (ATF6) and cyclic-AMP responsive element‑binding protein 3 (CREB3). Variants in the <i>MBTPS1</i> gene can lead to multiple clinically distinct disorders with different phenotypes, including spondyloepiphyseal dysplasia of Kondo-Fu type (SEDKF), Cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome, and Silver-Russell-like syndrome (SRS). This review presents the structural and functional characteristics of S1P, enumerates the relevant substrates and elucidates the spectrum of associated disorders resulting from pathogenic variants of <i>MBTPS1</i>, and discusses the correlations investigates the genotype-phenotype correlations underlying these distinct clinical manifestations.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914746","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}