Mammalian Genome最新文献

{"title":"Cancer-associated TRF1 mutations alter PARP1 interaction dynamics: an in silico study.","authors":"Apurwa Mishra, Trupti N Patel","doi":"10.1007/s00335-026-10211-w","DOIUrl":"https://doi.org/10.1007/s00335-026-10211-w","url":null,"abstract":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458371","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":"The North African maternal genetic diversity enriched by historical migrations: insights from a comprehensive analysis of complete mitogenomes.","authors":"Nasma Boumajdi, Houda Bendani, Lahcen Belyamani, Azeddine Ibrahimi","doi":"10.1007/s00335-026-10209-4","DOIUrl":"10.1007/s00335-026-10209-4","url":null,"abstract":"<p><p>North Africa has experienced significant gene flow throughout history, with Morocco occupying a strategic location at the crossroads of Africa and Europe. In this study, we compiled 869 complete mitogenome sequences from six North African populations to explore genetic diversity, haplogroup distributions, and phylogenetic relationships, with a specific emphasis on the Moroccan population. We obtained a high haplotype diversity across all populations, and neutrality tests yielded significant negative values, consistent with demographic expansion. We identified 56 haplogroups, dominated by U6, H, and L. Genetic differentiation between populations was low (FST = 0.001-0.014), and analysis of molecular variance indicated that most genetic variation occurs within populations, and reinforces the presence of a genetically cohesive Maghreb core. Phylogenetic and NeighborNet analyses showed that Moroccan sequences are widely distributed across haplogroups, with deep branching of macro-haplogroup L subclades, indicating early human migration patterns, including out-of-Africa dispersal and subsequent back-migrations. Bayesian demographic analysis of the prevalent haplogroups in Morocco revealed distinct evolutionary trajectories: an expansion of haplogroup L, a decline of U6, and an expansion of H. To complement the maternal perspective, we analyzed published Y-chromosome STR data from 2114 North African males. Haplotypic diversity remains high (> 0.97), and the haplogroup E-M81 predominates in Moroccan, Algerian, and Tunisian populations. Low pairwise Rst values further confirm the genetic homogeneity of North Africa and reinforce the strong cohesion of the Maghreb core. This study highlights a rich genetic heritage shaped by ancient and ongoing gene flow in North Africa.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444147","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":"Knockdown of SOX4 attenuates sepsis myocardial injury by inhibiting the EZH2/H3K27me3/SOCS3 axis.","authors":"Hongyan Zhao, Weirong Tao, Rong Huang, Jing Cao, Chao Xu","doi":"10.1007/s00335-026-10206-7","DOIUrl":"10.1007/s00335-026-10206-7","url":null,"abstract":"<p><p>Inhibition of SOX4 has been reported to ameliorate myocardial ischemic injury, yet its role in sepsis myocardial injury remains unknown. To explore the protective effects and mechanisms of SOX4 inhibition in septic myocardial injury. AC16 cardiomyocytes were exposed to LPS to mimic sepsis-induced myocardial injury. Cell viability was measured by CCK-8 assay, apoptosis by flow cytometry and TUNEL staining, and apoptosis-related proteins by western blot. The connection between SOX4 and EZH2 was validated using co-immunoprecipitation (co-IP) assay and immunofluorescence. Additionally, chromatin immunoprecipitation (ChIP) was employed to detect the enrichment of H3K27me3 in SOCS3 promoter region. The results showed that SOX4 and EZH2 were significantly elevated in septic patients, and their expression levels were positively correlated. In LPS-treated AC16 cardiomyocytes, the expressions of SOX4 and EZH2 increased, while the expression of SOCS3 decreased. Knockdown of SOX4 enhanced AC16 cell viability and inhibited LPS-induced apoptosis. SOX4 and EZH2 colocalized within AC16 cells, and co-IP assays confirmed their interaction. Elevated EZH2 expression reduced the protective impact of SOX4 knockdown in AC16 cells. Silencing EZH2 reduced the enrichment of H3K27me3 in SOCS3 promoter region and thereby promoting SOCS3 expression. Overexpression of SOCS3 promoted AC16 cell survival and partially reversed the damaging effect of EZH2 overexpression on cell survival. Animal experiments confirmed that knockdown of SOX4 attenuated myocardial injury in CLP sepsis mouse model. Knockdown of SOX4 reduces the H3K27me3 methylation level of the SOCS3 promoter by inhibiting EZH2 expression, thereby promoting SOCS3 expression and attenuating myocardial injury.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390410","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":"Regulation of humeral fracture healing by miR-21 through SMAD7-mediated activation of Wnt/β-catenin signaling.","authors":"Juan Liu, Hong Ren, Shuo Zhang, Guiyong Yu","doi":"10.1007/s00335-026-10208-5","DOIUrl":"10.1007/s00335-026-10208-5","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are key regulators of bone regeneration. We investigated the role of miR-21 in humeral fracture (HF) healing, focusing on its interaction with the SMAD7/Wnt/β-catenin signaling axis. Serum and tissue levels of miR-21 were analyzed in HF patients and healthy controls using qRT-PCR. A rat HF model was established, and agomiR-21 was administered to evaluate its effect on fracture healing. Histological analysis using hematoxylin and eosin (H&E) staining was performed to assess bone tissue morphology and fracture healing. In vitro, MC3T3-E1 osteoblasts were transfected with miR-21 mimics to assess cell viability (CCK-8), proliferation (EdU), apoptosis (flow cytometry), migration (Transwell assay), and osteogenic differentiation (Western blot). The downstream target of miR-21 was identified using bioinformatics and validated via luciferase reporter and RNA immunoprecipitation assays. Rescue experiments involving SMAD7 overexpression and Wnt/β-catenin inhibitors (DKK1) were conducted to explore the mechanism of action. Serum analysis revealed reduced β-catenin and phosphorylated GSK3β (p-GSK3β) levels in humeral fracture (HF) patients compared to healthy controls, indicating suppressed Wnt/β-catenin signaling. In MC3T3-E1 cells, miR-21 overexpression enhanced osteogenic markers and increased total β-catenin, active β-catenin, and p-GSK3β levels, confirming activation of the Wnt/β-catenin pathway. Dual-luciferase and expression analyses demonstrated that miR-21 directly targets SMAD7, a known Wnt pathway inhibitor. Co-transfection with SMAD7 reversed the effects of miR-21 on β-catenin activation, ALP activity, and osteogenic gene expression. Additionally, miR-21 knockdown impaired osteogenesis, further supporting its regulatory role. Importantly, in vivo, agomiR-21 treatment enhanced osteoblast activity and significantly promoted bone healing in a rat fracture model, reinforcing the therapeutic potential of miR-21-mediated SMAD7 suppression and Wnt/β-catenin pathway activation in bone regeneration. miR-21 promotes bone regeneration after humeral fracture by enhancing osteoblast function and activating Wnt/β-catenin signaling through direct inhibition of SMAD7.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390380","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 assembly of the Neotropical marsh rat Holochilus nanus (Cricetidae: Sigmodontinae) brings insights on B and sex chromosome evolution.","authors":"Camila Nascimento Moreira, Jordana Oliveira, Yatiyo Yonenaga-Yassuda, Valter Aragão do Nascimento, Ivan Rodrigo Wolf, Cesar Martins","doi":"10.1007/s00335-026-10205-8","DOIUrl":"10.1007/s00335-026-10205-8","url":null,"abstract":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372930","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":"Integrated multi-omics and machine learning prioritize key immune genes for multiple sclerosis risk prediction.","authors":"Ming Chen, Duran Zhao, Haiping Fan, Xiaojun Zeng, Wei Zhang, Lijuan Li, Wei Li","doi":"10.1007/s00335-026-10207-6","DOIUrl":"https://doi.org/10.1007/s00335-026-10207-6","url":null,"abstract":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344381","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":"LAPTM5 potentiates airway remodeling by regulating MAPKs-mediated airway smooth muscle cells' dysfunction.","authors":"Lijiao Jiang, Yaping Ying, Haihong Jin, Tingmin Zhou","doi":"10.1007/s00335-026-10204-9","DOIUrl":"10.1007/s00335-026-10204-9","url":null,"abstract":"<p><p>Airway remodeling is one of the hallmarks of asthma in which the dysregulation of airway smooth muscle cells (ASMCs) plays a part. However, the role of LAPTM5 in asthma is largely yet to be elucidated. In this study, the expression of LAPTM5 in ASMCs from the asthmatics and non-asthmatics was inspected using a publicly available dataset. The expression of LAPTM5 was next examined in ASMCs challenged by platelet-derived growth factor (PDGF). The establishment of LAPTM5 knockdown ASMCs was conducted with small interference RNA, and the proliferation, migration, and extracellular matrix production of ASMCs in the presence of PDGF were further determined. The activation of MAPK signaling was detected with western blot in LAPTM5 knockdown or overexpression ASMCs. Two MAPKs inhibitors, SB203580 and U0126, were employed to investigate the effects of MAPKs blockade on the proliferation, migration, and extracellular matrix production on LAPTM5-overexpressed ASMCs. The results revealed that the overexpression of LAPTM5 in the ASMCs of the asthmatics, and the knockdown of LAPTM5 in ASMCs suppressed PDGF-induced proliferation, migration, and extracellular matrix production. Furthermore, phosphor-p38 and -ERK enhanced by PDGF were reduced by LAPTM5 ablation. Pharmacal inhibition of MAPKs effectively abrogated the dysregulation of ASMCs induced by LAPTM5 overexpression in the presence of PDGF. Collectively, the expression of LAPTM5 is closely associated with the dysregulation of ASMCs and the consequent airway remodeling, and we proposed that LAPTM5 is a potential therapeutic target in asthma.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":"36"},"PeriodicalIF":2.7,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207323","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":"Hypoxia-induced circ_0017521 enhances glycolysis and promotes NSCLC progression via upregulating the PFKFB3/PI3K-AKT pathway.","authors":"Jian Zhu, Jin Yan, Yuanyuan Zhang, Xiaoli Zhu, Guoping Chen","doi":"10.1007/s00335-026-10202-x","DOIUrl":"10.1007/s00335-026-10202-x","url":null,"abstract":"<p><p>The hypoxic microenvironment is a critical feature of malignant progression in non-small cell lung cancer (NSCLC). However, the regulatory role of circular RNAs (circRNAs) in this context remains incompletely understood. Hypoxia-related circRNAs were screened by integrating GEO datasets, and the expression of circ_0017521 in hypoxia-treated cells was validated using qRT-PCR. RNase R digestion and actinomycin D assays were employed to assess its stability. Biological functions were evaluated through CCK-8, colony formation, Transwell, flow cytometry, and glycolytic metabolism assays. Dual-luciferase reporter, RNA pull-down, and rescue experiments were conducted to elucidate the circ_0017521/miR-532-3p/PFKFB3 axis. A nude mouse xenograft model was constructed. circ_0017521 was specifically upregulated in NSCLC tissues and hypoxia-treated cells, exhibiting remarkable stability compared to linear AKR1E2 and primarily localizing in the cytoplasm. Under hypoxic conditions, knockdown of circ_0017521 noticeably inhibited NSCLC cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and glycolysis, while promoting apoptosis. Mechanistically, circ_0017521 competitively bound to miR-532-3p, relieving its suppression of PFKFB3 and thereby activating the PI3K/AKT signaling pathway. Upregulation of PFKFB3 drove the expression of glycolytic enzymes (GLUT1, LDHA, HK2) and synergistically activated EMT. Animal experiments confirmed that silencing circ_0017521 suppressed tumor growth and glycolysis. This study revealed that hypoxia-induced circ_0017521 activated the PI3K/AKT pathway through the miR-532-3p/PFKFB3 axis, synergistically driving EMT and glycolysis, thereby promoting NSCLC progression.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":"37"},"PeriodicalIF":2.7,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207293","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 association study identifies significant SNPs for milk production and stature traits in Karan Fries cattle.","authors":"Pritam Pal, Ishmeet Kumar, Manisha Choudhary, Amritanshu Upadhyay, Irusappan Ilayaraja, Anil Chitra, Lal Muansangi, Gopal Gowane, T V Raja, Anupama Mukherjee, Sabyasachi Mukherjee","doi":"10.1007/s00335-026-10201-y","DOIUrl":"https://doi.org/10.1007/s00335-026-10201-y","url":null,"abstract":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":"35"},"PeriodicalIF":2.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125540","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":"Large-scale mouse mutagenesis identifies novel genes affecting vertebral anatomy.","authors":"Ximena Ibarra-Soria, Elizabeth Webb, John F Mulley","doi":"10.1007/s00335-025-10189-x","DOIUrl":"10.1007/s00335-025-10189-x","url":null,"abstract":"<p><p>We analyzed the International Mouse Phenotyping Consortium (IMPC) release 19 set of 8,539 phenotyped whole-gene knockouts to identify 204 genes that alter vertebral anatomy and development. These genes are broadly grouped into six categories based on their phenotype: \"vertebral number\" (22 genes); \"vertebral processes\" (35 genes); \"spine shape\" (16 genes); \"tail morphology\" (73 genes); \"vertebral form\" (62 genes); and \"somitogenesis\" (24 genes), with minimal overlap between groups. Gene expression analysis of somite trios across six developmental stages show that 182 of these genes are expressed in somites, and 60% of them show variable expression during somite maturation. A further 54% show expression changes between developmental stages. Fourteen of the 204 genes affecting vertebral anatomy have a vertebral phenotype as their only phenotype, and for 34 genes vertebral phenotypes represent ≥ 50% of their total phenotypes. We find no evidence for a previous association of the majority of these genes with vertebral defects, and have therefore identified an extensive set of novel candidate genes for association with vertebral malformations in humans, including vertebral fusions, numerical variation, and scoliosis.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":"34"},"PeriodicalIF":2.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12876460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125553","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}