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。

• Organoids and cortical tubers in Tuberous Sclerosis Complex show non-cell autonomous effects of second hit variants
  GSE294081Homo sapiens10 个样本2026-10-26

  Structural abnormalities are common causes of refractory epilepsy, and while progress has been made in understanding the genetic changes associated with these malformations, the pathogenic mechanisms often remain unclear. Dysregulation of the mechanistic target of rapamycin pathway has been found to contribute to a group of focal cortical dysplasia, and patients with Tuberous Sclerosis Complex often have several of these malformations. We used organoids generated from heterozygous patient-derived induced pluripotent stem cells and added isogenic stem cells with second hit variants to determine whether there are non-cell autonomous effects of the null cells. We found that the presence of null cells during differentiation led to abnormalities in neuronal development, which was due to secreted factors. Furthermore, null cells secreted extracellular vesicles containing proteins that inhibit the transcriptional coactivator, YAP1, and knockdown of one specific factor, AMOT, in null cells rescued neuronal differentiation and YAP1 expression. Finally, we analyzed cell type specific gene expression in malformations in patients with TSC and observed similar patterns of gene expression dysregulation. These data define a novel pathogenic mechanism underlying the development of focal brain malformations.
• EGR1 Binding to a Promoter G-Quadruplex Supports Early TNF Expression
  GSE292945Homo sapiens16 个样本2026-10-26

  G-quadruplexes (G4s) influence chromatin and transcription, but their roles in stimulus-induced rapid gene activation remain incompletely understood. Integration of public transcription-factor ChIP-seq, genome-wide G4 maps, and G4 pull-down/MS identified EGR1 as a G4-associated transcription factor. In vitro binding assays further demonstrated that EGR1 directly interacts with multiple G4 conformations, including parallel MYC G4, hybrid BCL2 G4, and antiparallel telomeric hTel21T18 G4. RNA-seq revealed an EGR1-dependent early LPS-induced inflammatory program. Integration with EGR1 ChIP-seq and G4access profiles prioritized TNF as a promoter-proximal EGR1–G4-associated target. A TNF promoter G4 showed BG4 enrichment and a parallel-like CD signature, and its mutation reduced BG4 signal, EGR1 occupancy, reporter activation, and early LPS-induced TNF expression. G4 ligands further disrupted EGR1 binding to the TNF G4 and reduced TNF expression. These findings reveal a promoter G4-dependent layer of EGR1-mediated TNF activation.