Gene最新文献

{"title":"Potential role of druggable gene SLC15A2 in keratinocyte hyperproliferation in psoriasis.","authors":"Chushan Huang, Pengsheng Chen, Xiaosong Chen","doi":"10.1016/j.gene.2026.150459","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150459","url":null,"abstract":"<p><p>Psoriasis is a chronic inflammatory skin disorder marked by abnormal keratinocyte proliferation and persistent immune activation. Identifying genetically supported druggable genes may offer new avenues for therapeutic development. We performed Mendelian randomization and colocalization analyses to identify druggable genes associated with psoriasis. These findings were then validated using an imiquimod-induced psoriasis-like mouse model, single-cell transcriptomics, and in vitro functional assays. SLC15A2 was identified as a gene potentially associated with psoriasis and was upregulated in psoriatic lesions. Single-cell analysis revealed that SLC15A2 was preferentially enriched in hyperproliferative keratinocyte subsets and correlated with cell-cycle activation and proliferation-related signaling pathways. Virtual knockout of SLC15A2 inhibited DNA replication and mitosis-related programs. In M5-stimulated HaCaT cells, knockdown of SLC15A2 decreased intracellular ROS levels and reduced keratinocyte proliferation and migration. Drug screening and molecular docking further indicated that SLC15A2 could be modulated by small molecules. Overall, these results suggest that SLC15A2 is a potential pathogenic gene with therapeutic relevance in psoriasis, providing insights into its role in keratinocyte hyperproliferation.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150459"},"PeriodicalIF":2.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant splicing caused by a homozygous AK2 c.498 + 1G > A variant in a patient with reticular dysgenesis and concurrent B-cell acute lymphoblastic leukemia.","authors":"Longkai He, Chunyan Zhao, Peng Lu, Xiaopeng Zhao","doi":"10.1016/j.gene.2026.150439","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150439","url":null,"abstract":"<p><p>Reticular dysgenesis (RD) is a rare autosomal recessive severe combined immunodeficiency characterized by profound neutropenia, T-cell lymphopenia and sensorineural hearing loss, and is caused by biallelic loss-of-function variants in AK2. We identified a homozygous AK2 splice-site variant (c.498 + 1G > A) in a boy with RD and concurrent B-cell acute lymphoblastic leukemia (B-ALL), a clinical combination not previously reported in association with an AK2 variant. An in vitro minigene assay showed that c.498 + 1G > A disrupts the canonical 5' splice donor site and generates an aberrant transcript carrying a 4-bp intronic insertion after exon 5, which causes a frameshift and introduces a premature termination codon; the transcript is predicted to be degraded by nonsense-mediated mRNA decay or, if translated, to yield a non-functional truncated protein, leading to loss of AK2 function. The variant was classified as pathogenic according to the ACMG/AMP criteria. As patient-derived material was unavailable, we re-analyzed publicly available RNA-seq data from AK2-knockout human hematopoietic stem and progenitor cells (GSE179320) and identified six hub genes (APOE, TREM2, CD68, CD36, IRF8 and CD163), which we further validated at the mRNA level in AK2-knockdown HL-60 cells, with IRF8 showing the most pronounced upregulation. This study characterizes the splicing defect caused by this variant and identifies candidate AK2-associated genes; the coexistence of RD and B-ALL is reported as a clinical observation requiring further investigation.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150439"},"PeriodicalIF":2.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects and mechanism of CYBB on the progression of multiple sclerosis: Evidence from bioinformatic analysis and experimental validation.","authors":"Minli Lv, Hongen Wei, Jiajia Zhao, Man Li, Liansheng Ma, Huizhong Gao","doi":"10.1016/j.gene.2026.150441","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150441","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil extracellular traps (NETs) are involved in the pathological progression of multiple sclerosis (MS), yet the intrinsic molecular mechanism by which NETs mediate the progression of MS remains unclear.</p><p><strong>Methods: </strong>Differentially expressed genes were screened by integrating Gene Expression Omnibus (GEO) datasets and NETs-related genes, and candidate biomarker genes for MS were identified using machine learning algorithms and receiver operating characteristic (ROC) curve analysis. Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, construction of competitive endogenous RNA (ceRNA) networks and drug-gene interaction networks were performed on these candidate biomarker genes. An experimental autoimmune encephalomyelitis (EAE) mouse model was established and intervened with cytochrome b-245 beta chain (CYBB) overexpression. Neurological scores, inflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], interleukin-18 [IL-18], and monocyte chemoattractant protein-1 [MCP-1]), oxidative stress indicators (malondialdehyde [MDA], superoxide dismutase [SOD], and catalase [CAT]), pathological damage, and pyroptosis-related proteins (NOD-like receptor pyrin domain-containing 3 [NLRP3], apoptosis-associated speck-like protein containing a CARD [ASC], and Caspase-1) were evaluated.</p><p><strong>Results: </strong>Four genes (CYBB, NF-kappa-B inhibitor alpha [NFKBIA], C-X-C motif chemokine receptor 4 [CXCR4], and IL1B) associated with MS were identified via bioinformatic analysis, among which CYBB exhibited the strongest immune-related correlation. The results of animal experiments revealed that EAE mice presented with weight loss, aggravated inflammation and oxidative stress, as well as elevated expression of pyroptosis-related proteins. CYBB overexpression significantly reversed these pathological alterations, suppressed proinflammatory cytokines and oxidative stress, and prevented the upregulation of pyroptosis-related proteins.</p><p><strong>Conclusion: </strong>CYBB overexpression alleviated inflammation and oxidative stress, suppressed the expression of pyroptosis-related proteins, and was associated with the amelioration of EAE pathological symptoms.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150441"},"PeriodicalIF":2.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1 expression reprograms tumor-associated macrophages polarization and influences progression and clinical outcomes in lung adenocarcinoma.","authors":"LinFeng Deng, YunFei Zhan, Miao Dai, JiangQi Xu, JianBang Shi","doi":"10.1016/j.gene.2026.150436","DOIUrl":"10.1016/j.gene.2026.150436","url":null,"abstract":"<p><strong>Background: </strong>Programmed death-1 (PD-1) is critical in reprogramming tumor-associated macrophage (TAM) polarization and is associated with lung adenocarcinoma (LUAD) progression and prognosis. LUAD is the most common histological subtype of non-small cell lung cancer (NSCLC), but checkpoint blockade response rates remain below 20 %. Understanding PD-1/programmed death-ligand 1 (PD-L1)-TAM interactions in the tumor microenvironment (TME) is needed to improve outcomes.</p><p><strong>Methods: </strong>Of 90 enrolled patients, 80 with pathologically confirmed LUAD (biopsy or post-surgery, January 2017-January 2019) were analyzed and divided into recurrence (n = 51) and non-recurrence (n = 29) groups. Receiver operating characteristic (ROC) analysis evaluated PD-1 for predicting recurrence; Kaplan-Meier curves analyzed PD-1 expression-disease-free survival (DFS) association. Flow cytometry assessed PD-1 effects on bone marrow-derived macrophage (BMDM) polarization. CCK-8 and Transwell assays assessed LA795 proliferation and migration.</p><p><strong>Results: </strong>High PD-1 expression was associated with significantly shorter median DFS than low expression. PD-1 on BMDMs promoted M2 polarization, suppressed phagocytosis, and enhanced LA795 proliferation and migration, suggesting PD-1 on TAMs fosters an immunosuppressive TME and accelerates progression.</p><p><strong>Conclusion: </strong>Elevated PD-1 expression correlates with poor prognosis in LUAD. In vitro, high macrophage PD-1 induced M2 polarization, inhibited phagocytosis, and indirectly promoted LUAD proliferation, migration, and epithelial-mesenchymal transition (EMT). These findings suggest PD-1 on TAMs may drive LUAD progression. However, these experiments were limited by a single murine tumor cell line, mouse BMDMs, and a conditioned medium system; moreover, missing treatment information means the clinical prognostic value of PD-1 requires further validation and cannot yet be directly applied to clinical risk assessment. Future in vivo animal experiments, multicellular models, and larger clinical cohorts with complete treatment information are needed to verify PD-1's role in the TME and its clinical potential.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150436"},"PeriodicalIF":2.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149107501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome analysis of patients with loss-of-function POGZ variants in four unrelated Chinese families","authors":"Yong Wu ,&nbsp;Na Liang ,&nbsp;Fengyuan He ,&nbsp;Bo Tan","doi":"10.1016/j.gene.2026.150070","DOIUrl":"10.1016/j.gene.2026.150070","url":null,"abstract":"<div><div>Intellectual disability (ID) and autism spectrum disorders (ASD) are complex neurodevelopmental disorders (NDDs) with a strong genetic component, and recent studies have highlighted the <em>POGZ</em> gene on chromosome 1q21.3 as a significant contributor, particularly linked to White-Sutton syndrome (WHSUS). <em>POGZ</em>-associated disorders are most commonly caused by heterozygous loss-of-function (LOF) variants, frequently arising <em>de novo</em>. In this study, we aimed to further this understanding by exploring novel pathogenic variants in the <em>POGZ</em> gene and their impact on the molecular landscape of NDDs. We conducted whole-exome sequencing (WES) in four unrelated Chinese families, each with a member diagnosed with ID. Four heterozygous LOF variants in <em>POGZ</em> were identified, including two frameshift deletions, one canonical splice-site substitution, and one nonsense variant. Parental testing was partially available for three probands and, in each case, was consistent with a <em>de novo</em> origin; parental data were unavailable for the remaining proband. Three out of the four LOF variants identified in this study are novel. Additionally, we undertook RNA sequencing and cohort analysis to delve into the molecular implications of <em>POGZ</em> haploinsufficiency. Aberrant expression was observed in 484 genes across the patients, a subset of which are involved in synaptic formation and function, offering insights into the involved molecular mechanisms. This study broadens the mutational spectrum of <em>POGZ</em>-related NDDs and underscores the crucial role of heterozygous <em>POGZ</em> LOF variants in the pathogenesis of ID and related conditions.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"991 ","pages":"Article 150070"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative mitochondrial genomics suggests lack of deep host-associated divergence in Pulex irritans (Arthropoda: Insecta): A one health perspective","authors":"Ying Xun ,&nbsp;Yan-Yan Peng ,&nbsp;Hany M. Elsheikha ,&nbsp;Yuan-Ping Deng ,&nbsp;Yu Zhuo ,&nbsp;Jian-Lei Zou ,&nbsp;Yi-Tian Fu ,&nbsp;Guo-Hua Liu","doi":"10.1016/j.gene.2026.150083","DOIUrl":"10.1016/j.gene.2026.150083","url":null,"abstract":"<div><div>The population structure of the generalist flea <em>Pulex irritans</em>, an important vector for zoonotic pathogens, remains poorly understood, limiting efforts to predict and control disease transmission across the human–animal–environment interface. We performed a comparative mitochondrial (mt) genomic analysis to assess for the presence of deep, host-associated genetic lineages in <em>P. irritans</em>. Complete mt genomes were sequenced from fleas collected from a human and a wild marmot using high-throughput sequencing, and compared with a published dog-derived mt genome from China. The newly assembled mt genomes were approximately 20.4 kb in length and exhibited high conservation, with pairwise nucleotide identities exceeding 98.7% and identical gene organization. Phylogenomic analyses placed all <em>P. irritans</em> isolates within a single, cohesive lineage (Bpp = 1.0; UFBoot = 100), showing no evidence of deep, host-specific substructuring. While the high genetic similarity (&gt;98%) is expected for conspecifics, the absence of deep phylogenetic splitting challenges the hypothesis of ancient, host-specific cryptic species. Ka/Ks ratios for all 13 protein-coding genes were &lt; 1, indicating strong purifying selection. Although limited by sample size, this study provides baseline genomic evidence suggesting that <em>P. irritans</em> likely does not comprise a complex of anciently diverged host-specialized lineages in this region. These findings highlight its potential as a versatile vector and emphasize the need for integrated One Health surveillance strategies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"991 ","pages":"Article 150083"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel NMD-escaping STAG2 variant associated with syndromic neurodevelopmental delay, growth failure, and distinctive dysmorphism: expanding the phenotype in male patients and literature review","authors":"Firoz Ahmad ,&nbsp;Sapna Sandal ,&nbsp;Alec Correa ,&nbsp;Murali Krishna ,&nbsp;Sowmya Sabnavis ,&nbsp;Syeda Kulsum ,&nbsp;Amisha Shah ,&nbsp;Meenu Angi ,&nbsp;Pooja Chaudhary ,&nbsp;Spandan Chaudhary ,&nbsp;Neeraj Arora","doi":"10.1016/j.gene.2026.150054","DOIUrl":"10.1016/j.gene.2026.150054","url":null,"abstract":"<div><div>We report an 8-year-old male from a consanguineous union presenting with global developmental delay, microcephaly, failure to thrive, and distinctive dysmorphic features (dolichocephaly, triangular face, malar flattening). His elder brother shared similar clinical and dysmorphic findings. The pattern of inheritance within the family (affected male siblings, subtle dysmorphism in mother and consanguinity) prompted consideration of both autosomal recessive and X-linked modes of inheritance. Whole exome sequencing (WES) identified a novel hemizygous <em>STAG2</em> frameshift variant (NM_001042750.2: c.3688_3689del; p.(Thr1230Hisfs*20)) in both brothers, inherited maternally. The variant is predicted to escape nonsense-mediated decay (NMD), potentially explaining survival, as complete <em>STAG2</em> loss of function mutations in hemizygous males are most often embryonic lethal. This represents the first report of NMD-escaping <em>STAG2</em> truncation in living males, expanding the mutational spectrum of STAG2-related disorders. The findings underscore the importance of considering hypomorphic <em>STAG2</em> variants in males with syndromic neurodevelopmental delay and dysmorphism.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"991 ","pages":"Article 150054"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A closed-loop microfluidic platform for enhanced gut organoid maturation via physicochemical control and morphodynamic feedback","authors":"Eric Kwame Owusu ,&nbsp;Donatien Sinzinkayo ,&nbsp;Yue Wang ,&nbsp;Na Liu ,&nbsp;Tao Yue","doi":"10.1016/j.gene.2026.150074","DOIUrl":"10.1016/j.gene.2026.150074","url":null,"abstract":"<div><div>Organoid technology has fundamentally transformed biomedical research, but remains limited by its inability to manipulate the in vivo physicochemical microenvironment. Here, we introduce a platform that bridges engineering and biology by elevating organoid-on-chip culture from a static process to a dynamic, precise science. We present a closed-loop microfluidic system that integrates on-demand CO₂ microreactions for spatiotemporal control of pH and oxygen, along with a novel suite of label-free, image-based morphodynamic sensors. These sensors include the dynamic deformation index (DDI), which quantifies structural stability; the curvature growth indicator (CGI), which tracks morphogenic activity; and the time-integrated shape entropy (TISE), which measures phenotypic variability. Together, the devices monitor the organoid’s state in real time and autonomously maintain physiological homeostasis. We demonstrate that this approach improves organoid health, achieving over 95% viability, reducing hypoxic core formation by 50% compared to static cultures, and enabling robust, physiologically relevant differentiation. Our versatile toolkit enables precise organoid interrogation and control, sets a new standard for intelligent in vitro systems, with significant implications for accelerating the fidelity of disease modelling, drug screening, and personalised medicine.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"991 ","pages":"Article 150074"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of C5AR1 polymorphisms with increased gastric cancer risk: mechanistic insights and therapeutic implications targeting JAK/STAT pathway","authors":"Zhongqi Wang ,&nbsp;Ying Jian ,&nbsp;Xiaomei Jiang ,&nbsp;Hongmei Zhang ,&nbsp;Zhi Zhang ,&nbsp;Xuemei Zhang","doi":"10.1016/j.gene.2026.150086","DOIUrl":"10.1016/j.gene.2026.150086","url":null,"abstract":"<div><div>While the pivotal role of C5a receptor 1 (<em>C5AR1</em>) in cancer immunity is well-established, its specific genetic and functional contributions to gastric cancer (GC) remain elucidated. This study investigates the correlation between <em>C5AR1</em> polymorphisms with GC risk, alongside exploring the underlying molecular mechanisms. Genotyping was conducted utilizing a PCR-based method for identifying restriction fragment length polymorphisms (RFLP). Dual-luciferase reporter assays assessed the transcriptional activity of the rs62128435 and rs8103584 variants. Detecting the impact of <em>C5AR1</em> gene knockdown on cell growth, movement, and spread in NUGC-4 and HGC-27 GC cells by CCK-8, colony formation, and Transwell assays. Western blot was utilized to discover the role of <em>C5AR1</em> in the JAK/STAT signaling pathway. Individuals carrying <em>C5AR1</em> rs62128435 CC and rs8103584 CC genotypes were each associated with elevated GC risk. The <em>C5AR1</em> rs62128435 CC genotype and rs8103584 CC genotype altered GC risk among males, older individuals, smokers, and drinkers. Reporter assays revealed that rs62128435 C and rs8103584 T containing plasmids exhibited higher luciferase activity compared to their counterparts. <em>C5AR1</em> suppressed the proliferation, colony-forming capacity, and migration of GC cells, and reduced the phosphorylation of JAK2 and STAT3, linking <em>C5AR1</em> to JAK/STAT pathway regulation. This study identifies <em>C5AR1</em> polymorphisms as novel risk factors for GC, linking them to regulated transcriptional activity and regulation of JAK/STAT signal. It also highlights the role of gene-environment interactions, such as smoking, alcohol status, in modulating cancer susceptibility. These findings advance understanding of GC pathogenesis and offer a foundation for personalized risk assessment and potential targeted therapies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"991 ","pages":"Article 150086"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential early tubular injury in minimal Change disease and Focal segmental Glomerulosclerosis: A Multifaceted analysis","authors":"Yiting Zhao ,&nbsp;Jianbo Qing ,&nbsp;Xiao Wang ,&nbsp;Yafeng Li ,&nbsp;Junnan Wu","doi":"10.1016/j.gene.2026.150043","DOIUrl":"10.1016/j.gene.2026.150043","url":null,"abstract":"<div><div>Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) represent the primary types of podocytopathies, affecting individuals of all age groups worldwide. Diagnosis of MCD and FSGS relies on renal biopsy, yet their pathological manifestations are remarkably similar in the early stages, often leading to misdiagnoses and incorrect treatment. Currently, there is no economical and accurate discrimination method available. We collected renal tissue from early-stage MCD and FSGS patients for single-nucleus RNA sequencing ( snRNA-seq), focusing specifically on proximal tubular (PT) cells. Our findings indicate that, in the early stages, PT cells in FSGS exhibit more pronounced molecular damage, and FSGS also displays the highest injured PT (IPT) cell ratio, while PT cells in MCD show gene expression patterns more akin to those of healthy controls. Further analyses of early-stage transcription factor (TF) regulatory networks and cell communication differences revealed that the transcription factor BCL3 is significantly activated in IPT cells from FSGS, whereas HNF4A is the most active in MCD IPT cells. Additionally, the HGF-MET ligand-receptor pair was identified as a specific communication pathway between FIB and PT cells in FSGS, whereas the TGFA-EGFR ligand-receptor pair is crucial for cell communication in MCD PT cells. By constructing gene co-expression networks (GCNs), we found that <em>SLC7A8</em> is significantly elevated in both IPT and all PT types in MCD compared to FSGS and controls. This expression pattern was further supported by multiplex immunohistochemistry (MIHC). Collectively, these findings suggest that SLC7A8 may serve as a potential biomarker to assist in the early pathological differentiation of MCD and FSGS.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"988 ","pages":"Article 150043"},"PeriodicalIF":2.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}