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。

• Oxidative Stress Potentiates a STAT1–APOL1 Feedforward Loop and Governs Disease Severity in APOL1-Mediated Kidney Disease
  GSE300326Mus musculus8 个样本2026-10-26

  Introduction: Apolipoprotein L1 (APOL1) risk variants (G1 and G2) confer immunity against Trypanosoma infection but markedly increase susceptibility to progressive kidney disease. However, only a subset of biallelic risk-variant carriers develops disease progression, distinct from murine models. Here, we evaluated molecular drivers of progressive disease using a model that reflected the low human disease penetrance. Methods: To investigate the heterogeneity of APOL1-mediated kidney disease, we generated novel APOL1 bacterial artificial chromosome transgenic mice with doxycycline-inducible systemic IFNγ expression (G0- or G1-IFNγ mice). Podocyte-specific transcriptomics using translating ribosome affinity purification (TRAP-seq) and single-cell spatial transcriptomics via 10x Genomics Xenium In Situ platform were performed. Mechanistic validation and analysis of factors regulating APOL1 upregulation were conducted in primary podocytes and subsequently validated in human and mouse kidney biopsy specimens via immunofluorescence. Results: A subset of G1-IFNγ mice developed severe albuminuria and focal segmental glomerulosclerosis, which strongly correlated with the magnitude of APOL1 upregulation. By pairing TRAP-seq with single-cell spatial transcriptomic data, we identified mitochondrial dysfunction and JAK-STAT signaling as a central mediator of podocyte injury. In primary podocytes, APOL1 risk variants triggered mitochondrial-derived oxidative stress, establishing a self-amplifying STAT1-APOL1 feedforward loop that further enhances APOL1 expression and APOL1 oligomerization. This pathogenic loop was consistently enriched in podocytes from both G1-IFNγ mice and in kidney biopsy specimens from patients with APOL1-mediated focal segmental glomerulosclerosis, demonstrating translational relevance. Conclusions: Our findings suggest that biallelic risk variants initiate an oxidative stress-induced positive feedback loop which promotes APOL1 upregulation and STAT1 phosphorylation, thereby contributing to disease susceptibility and outcome.

  单细胞空间转录组
• Glial Fatp1 mediates chenodeoxycholic acid signaling in brain aging
  GSE295894Drosophila melanogaster9 个样本2026-10-26

  Aging is shaped by interorgan metabolic communication, yet the mechanism linking peripheral metabolism to brain aging remain poorly understood. Here, we identify a fat body–brain pathway connecting age-associated accumulation of chenodeoxycholic acid (CDCA) to glial inflammation and functional decline. In Drosophila, the fat body cytochrome P450 enzyme Cyp6w1 contributes to cholesterol-derived CDCA production, while the fatty acid transporter Fatp1 facilitates CDCA uptake into glial cells. Intracellular CDCA accumulation activates mTOR and JAK-STAT signaling, promoting neuroinflammation. Fatp1 knockdown in ensheathing glia reduces CDCA accumulation, attenuates inflammatory signaling, and improves healthspan in wild-type and Alzheimer’s disease model flies. Pharmacological inhibition of FATP1 or mTOR also reduces CDCA-induced neuroinflammatory responses and behavioral impairment in mice. The findings link peripheral bile acid metabolism to glial signaling and identify Fatp1-mediated CDCA transport as a potential target for modulating brain aging.