GEO 数据集

主题由标题与摘要自动归类；样本量为数据集标注之和，SuperSeries 可能与其 SubSeries 重复计算。

• Lamin B1 physically regulates neuronal migration by modulating nuclear deformability in the developing cortex
  GSE347519Mus musculus18 个样本2026-10-29

  Neuronal migration positions billions of neurons to form a functional brain. Effective navigation through the cortex requires precise regulation of nuclear mechanics in migrating neurons. We demonstrate that Lamin B1 (LB1) regulates neuronal migration by modulating nuclear deformability. Elevated LB1 in neurons halted migration in vivo, without affecting laminar identity or pre-migratory gene expression. Mispositioned neurons subsequently caused electrophysiological defects in the brain. In vitro, increased LB1 raised nuclear stiffness, as measured by atomic force microscopy, and reduced neuronal motility in confined environments reconstituted with microchambers. Computational modeling predicted a temporal link between nuclear deformation and increased migration velocity, which was validated experimentally through live imaging. Notably, cerebral organoid assays using induced pluripotent stem cells established from patients with LMNB1 duplication exhibited impaired neuronal migration in a human model. Collectively, these findings establish LB1 as a critical regulator of nuclear mechanics, ensuring accurate spatiotemporal positioning of neurons.

  计算与 AI
• Novel WRN Exon 10 Skipping Mutation Triggers Progerin Accumulation and Premature Aging
  GSE351663Mus musculus6 个样本2026-10-26

  Werner Syndrome (WS) is an autosomal recessive disorder characterized by premature aging and increased susceptibility to various age-related diseases, predominantly caused by mutations in the WRN gene. This study investigated a Chinese patient with WS and partial lipoatrophic diabetes mellitus, aiming to identify a novel pathogenic variant in the WRN gene. High-throughput sequencing was conducted on genomic DNA from a blood sample. The identified homozygous variant (WRN_intron9 c.1270-1G>C) was confirmed, and its pathogenicity was assessed through in silico predictions, structural modeling, and cell function assays. The variant's effect on exon skipping was analyzed, and cellular assays were performed to validate the induced phenotype. The study identifies a novel WRN variant as a potential pathogenic factor in the patient. Simulations predict that the WRN_intron9 c.1270-1G>C mutation triggers exon 10 skipping, deleting one of the two highly homologous peptide regions encoded by exon 10 and exon 11 respectively. Cellular assays confirm senescent phenotype induction and human progerin accumulation, leading to premature cellular senescence.

  计算与 AI
• A GABA-producing Limosilactobacillus fermentum ameliorates autism-like behaviors associated with altered gut microbial metabolism and cortical GABA signaling
  GSE351532Mus musculus24 个样本2026-10-26

  Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social deficits and restricted, repetitive behaviors. Altered excitation/inhibition (E/I) balance, including impaired γ-aminobutyric acid (GABA) ergic signaling, has been implicated as a key pathophysiological feature of ASD. Although growing evidence implicates the gut–brain axis in regulating neural function, the strain-specific microbial mechanisms that influence central GABAergic signaling remain incompletely understood. Here, we evaluated whether Limosilactobacillus fermentum IMB064, identified by genome-based in silico screening, could modulate ASD-associated symptoms in BTBR mice, a widely used ASD model. Oral administration of IMB064 significantly reduced repetitive behaviors and improved social novelty preference in BTBR mice. Taxa-resolved metabolic flux modeling of the gut microbiome based on metagenomic profiling indicated that IMB064 administration was associated with alterations in gut microbial metabolic potential, including increased potential for GABA production, particularly among GABA-producing taxa such as Limosilactobacillus. Transcriptomic analysis further revealed a cortex-selective response to IMB064, with 1,552 cortical genes significantly altered and enriched in neuronal signaling pathways. These differentially expressed genes significantly overlapped with human ASD-associated cortical co-expression modules identified by weighted gene co-expression network analysis (WGCNA) and with chromatin-regulatory gene networks. Consistent with this region-specific molecular response, IMB064 significantly increased cortical GABA levels, with a trend toward an increased GABA-to-glutamate ratio, whereas no significant changes were observed in the striatum. Collectively, these findings indicate that the GABA-producing strain IMB064 alters gut microbial metabolic potential and is associated with cortex-selective changes in GABA-related neurochemical profiles, accompanied by modulation of human ASD-relevant gene networks and improvement of ASD-like behavioral phenotypes, supporting IMB064 as a promising live biotherapeutic candidate for ASD.

  计算与 AI