Human molecular genetics最新文献_第6页

A case report of SPONASTRIME dysplasia with novel TONSL mutation: genetic analysis, clinical manifestations, and the effect of growth hormone treatment. SPONASTRIME发育不良伴新型TONSL突变1例：基因分析、临床表现及生长激素治疗效果。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-09-19 DOI: 10.1093/hmg/ddaf128

Minglan Yao, Cai Zhang, Sujuan Li, Anran Tian, Furong Liang, Xiaoping Luo

{"title":"A case report of SPONASTRIME dysplasia with novel TONSL mutation: genetic analysis, clinical manifestations, and the effect of growth hormone treatment.","authors":"Minglan Yao, Cai Zhang, Sujuan Li, Anran Tian, Furong Liang, Xiaoping Luo","doi":"10.1093/hmg/ddaf128","DOIUrl":"10.1093/hmg/ddaf128","url":null,"abstract":"SPONASTRIME dysplasia is a rare genetic disorder characterized by short stature, facial abnormalities, vertebral issues, and bone striations, caused by recessive mutations in the TONSL gene. We reported a 6-year-old boy with characteristic clinical features of SPONASTRIME dysplasia, accompanied by neutropenia. Genetic analysis revealed biallelic variants in TONSL: mother-inherited c.1289del (p.Gln430ArgfsTer13) and father-inherited c.1961G > C (p.Arg654Pro), both of which were previously unreported. We predicted the c.1289del (p.Gln430ArgfsTer13) variant as likely pathogenic in silico analysis, while the c.1961G > C (p.Arg654Pro) variant as uncertain pathogenicity in silico analysis, and the pathogenicity was confirmed by functional studies in transfected HEK 293 T cells. Six-month growth hormone therapy was administered to the patient after confirmed diagnosis, with limited improvement. These findings have important implications for the diagnosis and treatment of the disease.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1665-1673"},"PeriodicalIF":3.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Novel TMEM53 missense variant generated a new ubiquitination site and cause Craniotubular dysplasia, Ikegawa type. 新的TMEM53错义变体产生新的泛素化位点并导致池川型颅管发育不良。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-09-03 DOI: 10.1093/hmg/ddaf121

Ying Peng, Zhengqing Wan, Kai Li, Zhen Liu, Jing Chen, Ai Hu, Silong Wang, Rui Liu, Bo Li, Xiao Mao, Ming Wu

引用次数: 0

A discrete region of the D4Z4 is sufficient to initiate epigenetic silencing. D4Z4的一个离散区域足以启动表观遗传沉默。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-09-03 DOI: 10.1093/hmg/ddaf114

Ellen M Paatela, Faith G St Amant, Danielle C Hamm, Sean R Bennett, Taranjit S Gujral, Silvère M van der Maarel, Stephen J Tapscott

{"title":"A discrete region of the D4Z4 is sufficient to initiate epigenetic silencing.","authors":"Ellen M Paatela, Faith G St Amant, Danielle C Hamm, Sean R Bennett, Taranjit S Gujral, Silvère M van der Maarel, Stephen J Tapscott","doi":"10.1093/hmg/ddaf114","DOIUrl":"10.1093/hmg/ddaf114","url":null,"abstract":"The DUX4 transcription factor is briefly expressed in the early embryo and is epigenetically repressed in somatic tissues. Loss of epigenetic repression can result in the aberrant expression of DUX4 in skeletal muscle and can cause facioscapulohumeral dystrophy (FSHD). Multiple factors have been identified as necessary to maintain epigenetic silencing of DUX4 in skeletal muscle, but whether specific sequences at the DUX4 locus are sufficient for initiating epigenetic silencing has not been known. We cloned fragments of the D4Z4 macrosatellite repeat, the DNA region that encompasses the DUX4 retrogene, adjacent to a reporter driven by a constitutive promoter and identified a single fragment sufficient to epigenetically repress reporter gene expression. Previously identified repressors of DUX4 expression-SETDB1, ATF7IP, SIN3A/B, and LRIF1-were necessary for silencing activity and p38 inhibitors enhanced suppression. These findings identify a key regulatory sequence for D4Z4 epigenetic repression and establish a model system for mechanistic and discovery studies.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1526-1540"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Novel neurofilament light (Nefl) E397K mouse models of Charcot-Marie-tooth type 2E (CMT2E) present early and chronic axonal neuropathy. 新型神经丝光（Nefl） E397K小鼠模型的Charcot-Marie-tooth型2E （CMT2E）存在早期和慢性轴索神经病变。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-09-03 DOI: 10.1093/hmg/ddaf116

Dennis O Pérez-López, Audrey A Shively, F Javier Llorente Torres, Mohammed T Abu-Salah, Michael L Garcia, W David Arnold, Monique A Lorson, Christian Lorson

{"title":"Novel neurofilament light (Nefl) E397K mouse models of Charcot-Marie-tooth type 2E (CMT2E) present early and chronic axonal neuropathy.","authors":"Dennis O Pérez-López, Audrey A Shively, F Javier Llorente Torres, Mohammed T Abu-Salah, Michael L Garcia, W David Arnold, Monique A Lorson, Christian Lorson","doi":"10.1093/hmg/ddaf116","DOIUrl":"10.1093/hmg/ddaf116","url":null,"abstract":"Charcot-Marie-Tooth (CMT) is the most common hereditary peripheral neuropathy with an incidence of 1:2500. CMT2 clinical symptoms include distal muscle weakness and atrophy, sensory loss, toe and foot deformities, with some patients presenting with reduced nerve conduction velocity. Mutations in the neurofilament light chain (NEFL) gene result in a specific form of CMT2 disease, CMT2E. NEFL encodes the protein, NF-L, one of the core intermediate filament proteins that contribute to the maintenance and stability of the axonal cytoskeleton. To better understand the underlying biology of CMT2E disease and advance the development of therapeutics, we generated a Nefl+/E397K mouse model. While the Nefl+/E397K mutation is inherited in a dominant manner, we also characterized NeflE397K/E397K mice to determine whether disease onset, progression or severity would be impacted. Consistent with CMT2E, lifespan was not altered in these novel mouse models. A longitudinal electrophysiology study demonstrated significant in vivo functional abnormalities as early as P21 in distal latency, compound muscle action potential (CMAP) amplitude and negative area. A significant reduction in the sciatic nerve axon area, diameter, and G-ratio was also present as early as P21. Through the twelve months measured, disease became more evident in all assessments. Collectively, these results demonstrate an early and robust in vivo electrophysiological phenotype and axonal pathology, making Nefl+/E397K and NeflE397K/E397K mice ideal for the evaluation of therapeutic approaches.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1541-1552"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Functional analysis of novel MMP21 gene compound heterozygous mutations in a prenatal case with heterotaxy. 一个产前异交病例中新型MMP21基因复合杂合突变的功能分析。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-09-03 DOI: 10.1093/hmg/ddaf122

Quan Chen, Hao Zhang, Xue Li, Lin Liu, Zhiqing Hu, Zhihong Xu

{"title":"Functional analysis of novel MMP21 gene compound heterozygous mutations in a prenatal case with heterotaxy.","authors":"Quan Chen, Hao Zhang, Xue Li, Lin Liu, Zhiqing Hu, Zhihong Xu","doi":"10.1093/hmg/ddaf122","DOIUrl":"10.1093/hmg/ddaf122","url":null,"abstract":"Background: Heterotaxy is a class of congenital disorders resulting from failure to establish normal left-right asymmetry during embryonic development, which causes abnormal positioning and morphology of the thoraco-abdominal organs. The pathogenesis of heterotaxy is multifactorial and involves both genetic and environmental factors. With the application of whole exome sequencing (WES), pathogenic biallelic variants in the matrix metalloproteinase 21 (MMP21) gene have been increasingly identified in patients with heterotaxy and congenital heart defects.Methods: In this study, two novel compound heterozygous MMP21 variants, specifically, a frame shift variant c.414del; p.(Arg139Glufs*38) and an intron variant c.980-16 T > A, were identified in a fetus diagnosed with heterotaxy through WES. In vitro assays were performed to evaluate the effects of the two variants.Results: Western blotting revealed that c.414del variant resulting in premature translation termination and the production of a truncated protein, which was found to completely lack the hemopexin-like repeats domain and to almost entirely lose its catalytic domain. In silico analysis and minigene assay suggested that c.980-16 T > A variant lead to aberrant splicing pattern including exon 5 skipping and 14-bp intron retention. To our knowledge, both of the two variants were reported for the first time, and the c.980-16 T > A is the first intron variant founded to affect splicing in the MMP21 gene.Conclusion: Functional analysis confirmed the pathogenicity of the two variants. Our findings expand the mutational spectrum of MMP21 and provide support for the critical role of MMP21 gene in heterotaxy and congenital heart defects.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1584-1591"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A novel mutation in CFAP58 leads to MMAF in humans and mice by disrupting CP assembly. CFAP58的一种新突变通过破坏CP组装导致人类和小鼠的MMAF。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-09-03 DOI: 10.1093/hmg/ddaf070

Tanveer Abbas, Huan Zhang, Hao Yin, Ma Ao, Ye Jingwei, Nisar Ahmad, Ranjha Khan, Ghulam Murtaza, Ansar Hussain, Fazal Rahim Dawar, Imtiaz Ali, Aurang Zeb, Wasim Shah, Hui Ma, Yuanwei Zhang, Qinghua Shi

{"title":"A novel mutation in CFAP58 leads to MMAF in humans and mice by disrupting CP assembly.","authors":"Tanveer Abbas, Huan Zhang, Hao Yin, Ma Ao, Ye Jingwei, Nisar Ahmad, Ranjha Khan, Ghulam Murtaza, Ansar Hussain, Fazal Rahim Dawar, Imtiaz Ali, Aurang Zeb, Wasim Shah, Hui Ma, Yuanwei Zhang, Qinghua Shi","doi":"10.1093/hmg/ddaf070","DOIUrl":"10.1093/hmg/ddaf070","url":null,"abstract":"Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of male infertility, linked to defective spermiogenesis. Several flagella-associated proteins have been identified as crucial for the proper organization of the sperm flagellar axoneme. We identify a novel homozygous mutation in the CFAP58 gene (c.562C > T, p. R188*) that co-segregates with the multiple morphological abnormalities of the flagella (MMAF) phenotype in two unrelated consanguineous families from Pakistan. To validate the pathogenicity of this mutation, we developed a Cfap58 mutant mouse model to mimic the patient mutation. The Cfap58M/M mice exhibited infertility and recapitulated the MMAF phenotype observed in human patients. Transmission electron microscopy (TEM) analysis revealed the absence of the central pair (CP) of microtubules in the axonemal structure of sperm flagella. Further analysis demonstrated that the CFAP58 mutation disrupts CP assembly during spermiogenesis, leading to disorganization of axonemal proteins in both human and mouse sperm flagella. Our findings underscore the essential and conserved role of CFAP58 in sperm axoneme assembly and suggests that CFAP58 can serve as a genetic screening marker in the diagnosis and genetic counseling of MMAF and male infertility.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1575-1583"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Copy number variants and their implications for developmental and behavioural problems in cleft lip and/or palate. 拷贝数变异及其对唇裂和/或腭裂发育和行为问题的影响。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-09-03 DOI: 10.1093/hmg/ddaf115

Alexandros Rammos, Rachel Blakey, Charlotte A Dennison, Sarah J Lewis, Nabila Ali, Amy Davies, Yvonne Wren, Kerry Humphries, Jonathan Sandy, Elliott Rees, Kimberley Marie Kendall, Gemma C Sharp, Michael J Owen, Marianne B M van den Bree, Evie Stergiakouli

{"title":"Copy number variants and their implications for developmental and behavioural problems in cleft lip and/or palate.","authors":"Alexandros Rammos, Rachel Blakey, Charlotte A Dennison, Sarah J Lewis, Nabila Ali, Amy Davies, Yvonne Wren, Kerry Humphries, Jonathan Sandy, Elliott Rees, Kimberley Marie Kendall, Gemma C Sharp, Michael J Owen, Marianne B M van den Bree, Evie Stergiakouli","doi":"10.1093/hmg/ddaf115","DOIUrl":"10.1093/hmg/ddaf115","url":null,"abstract":"Cleft lip and/or palate (CL/P) is the most common craniofacial congenital anomaly and has been associated with higher risk of neurodevelopmental and behavioural problems indicating potential shared genetic factors between CL/P and neurodevelopmental disorders. In this study, we aimed to determine the prevalence of neurodevelopmental copy number variants (CNV) in children with CL/P and their link to early developmental and behavioural problems. Using data from the Cleft Collective, the largest UK-based national cohort study of children with CL/P, we determined the rates of neurodevelopmental CNVs in children with CL/P comparing them to the general population, explored differences by cleft type and investigated risk of developmental delays and behavioural problems among those with CL/P and neurodevelopmental CNVs. Children with CL/P had a higher prevalence of neurodevelopmental CNVs than participants in four population-based samples (3.7% vs 2.3% in the Avon Longitudinal Study of Parents and Children (ALSPAC), 2.0% in Born in Bradford (BiB), 2.3% in Millenium Cohort Study (MCS), 1.7% in UK Biobank, ORs(95%CIs): ALSPAC = 1.56(1.18-2.06), BiB = 1.84(1.37-2.45), MCS = 1.59(1.19-2.11), UK Biobank = 2.15(1.68-2.71). Children with cleft palate only were 3 times more likely to have a neurodevelopmental CNV (95%CIs1.50-6.59, p = 0.03) than children with cleft lip only. Furthermore, children with CL/P and neurodevelopmental CNVs were more likely to experience early developmental delays and behavioural problems by age 5 compared to children with CL/P and without neurodevelopmental CNVs. These findings highlight that genetic testing ascertaining the presence of neurodevelopmental CNVs might be helpful in early identification of developmental needs in children with CL/P.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1563-1574"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Pathology of three ALS patients with FUS variants, including one likely benign Q23L variant lacking FUS inclusions. 3例ALS患者FUS变异的病理分析，其中1例可能是良性的Q23L变异，缺乏FUS包涵体。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-09-03 DOI: 10.1093/hmg/ddaf119

Erica Stenvall, Kornelia Åman Grönlund, Zdenek Rohan, Per Zetterström, Angelica Nordin, Karin Forsberg

{"title":"Pathology of three ALS patients with FUS variants, including one likely benign Q23L variant lacking FUS inclusions.","authors":"Erica Stenvall, Kornelia Åman Grönlund, Zdenek Rohan, Per Zetterström, Angelica Nordin, Karin Forsberg","doi":"10.1093/hmg/ddaf119","DOIUrl":"10.1093/hmg/ddaf119","url":null,"abstract":"Fused in sarcoma (FUS) is an RNA-binding protein implicated in juvenile amyotrophic lateral sclerosis (ALS). Mutations in the FUS gene, particularly those affecting the nuclear localization signal (NLS), impair nuclear import and lead to cytoplasmic accumulation of FUS inclusions in motor neurons. However, the pathological and clinical significance of FUS variants outside the NLS remains less understood. Here, we describe clinical and histopathological findings from three ALS patients carrying FUS variants: two with NLS-region variants (R495X and P525L), and one with a variant in the N-terminal region outside the NLS (Q23L). The patients carrying NLS variants presented with aggressive, juvenile-onset spinal and bulbar ALS, characterized primarily by lower motor neuron involvement and rapid disease progression. In contrast, the Q23L patient exhibited a slowly progressive disease course, with predominantly upper motor neuron signs. Neuropathological analysis revealed cytoplasmic FUS inclusions in motor neurons of patients with NLS variants, consistent with typical FUS pathology. In contrast, the Q23L patient lacked FUS inclusions and instead displayed pTDP-43 pathology in the hippocampus, neocortex (including the motor cortex), nucleus olivaris, lentiform nucleus, striatum, and some lower motor neurons. Taken together, these results suggest that Q23L is most likely a benign variant. As antisense oligonucleotides (ASOs) targeting FUS are currently being explored in clinical trials, further neuropathological investigations are needed to determine whether ASO-mediated FUS silencing would be effective for patients carrying FUS variants outside the NLS region.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1553-1562"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 novel splicing variant in TECTA associated with prelingual autosomal dominant nonsyndromic hearing loss via dominant-negative effect. 一种新的TECTA剪接变异与语前常染色体显性非综合征性听力损失相关。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-09-03 DOI: 10.1093/hmg/ddaf109

Yan Yang, YuanPing Xiong, Hua Lai, Chuanxin Feng, ZhongFa Chen, YaJuan Huang, Zhen Guo, XinYu Li, Laipeng Luo, Feng Zhao, Ping Wu, Haiyan Luo, Yanqiu Liu, Yuhe Liu, Yongyi Zou

{"title":"A novel splicing variant in TECTA associated with prelingual autosomal dominant nonsyndromic hearing loss via dominant-negative effect.","authors":"Yan Yang, YuanPing Xiong, Hua Lai, Chuanxin Feng, ZhongFa Chen, YaJuan Huang, Zhen Guo, XinYu Li, Laipeng Luo, Feng Zhao, Ping Wu, Haiyan Luo, Yanqiu Liu, Yuhe Liu, Yongyi Zou","doi":"10.1093/hmg/ddaf109","DOIUrl":"10.1093/hmg/ddaf109","url":null,"abstract":"The TECTA gene encodes α-tectorin, the major non-collagenous glycoprotein of the tectorial membrane, and plays a critical role in intracochlear sound transmission. Unsurprisingly, mutations in TECTA underlie hearing loss in both mice and humans. Two forms of hearing loss are linked to TECTA mutations: DFNA8/12 (autosomal dominant) and DFNB21 (autosomal recessive). Using a combination of clinical examination, pedigree analysis, exome sequencing, and functional studies, we identified a novel aberrant splicing variant, c.5999G > A (p.Gly2000Glu), in TECTA as the cause of autosomal dominant hearing loss in five-generation kindred of Chinese descent and provided prenatal diagnosis for the family. To investigate whether the variant acts via a a dominant-negative effect, consistent with pathogenesis observed in mouse models, we performed in vivo RNA analysis. Our data demonstrated that the variant altered RNA splicing, specifically causing aberrant splicing of exon 20 and resulting in two in-frame deletions. Quantitative real-time polymerase chain reaction revealed no significant reduction in mRNA levels in lymphoblasts derived from individuals harboring the TECTA c.5999G > A (p.Gly2000Glu) variant or the TECTA c.5383 + 6 T > A splicing variant, previously shown to result in exon 16 skipping. This study confirms the involvement of an aberrant splicing mutation in TECTA in autosomal dominant nonsyndromic hearing loss, expands the mutational landscape of DFNA8/12 to include coding variants that alter RNA splicing, and underscores the importance of investigating splicing effects of coding variants.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1517-1525"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Single cell analysis of pan-cancer tumor microenvironment in immunotherapy. 免疫治疗中泛癌肿瘤微环境的单细胞分析。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-08-21 DOI: 10.1093/hmg/ddaf101

Feng Li, Ke Xue, Liying Pei, Yu Sun, Zhe Chen, Yifang Zhang, Kaiyue Song, Wensong Liu, Quan Qi, Xue Gong, Jing Li, Yanjun Xu

{"title":"Single cell analysis of pan-cancer tumor microenvironment in immunotherapy.","authors":"Feng Li, Ke Xue, Liying Pei, Yu Sun, Zhe Chen, Yifang Zhang, Kaiyue Song, Wensong Liu, Quan Qi, Xue Gong, Jing Li, Yanjun Xu","doi":"10.1093/hmg/ddaf101","DOIUrl":"10.1093/hmg/ddaf101","url":null,"abstract":"The high heterogeneity of tumor microenvironment (TME) is a key factor affecting immunotherapy. We integrated immunotherapy related scRNA-seq and bulk datasets to analyze the TME, mine key factors and dissect the mechanism in immunotherapy. Analyzing the cell composition of TME in cancer immunotherapy, we revealed key TME cell types, including B cells, CD8+ T cells and fibroblasts. Through cell subsets identification, pseudo-time sequence and functional status analysis of malignant cells, it was found that the functional status of malignant cell was heterogeneous under different immunotherapy conditions. Key cellular interactions in cancer immunotherapy were also revealed. Further, 16 marker genes and 6 marker cell types of cancer immunotherapy were identified, and then gene and cell model were constructed to predict the immunotherapy response of individuals, and the model were evaluated based on multiple independent validation datasets. This study can provide important guidance for improving the efficiency and understanding the mechanism of cancer immunotherapy.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1446-1457"},"PeriodicalIF":3.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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