详细内容（前10条）

1. ⭐ GSE292799 单细胞转录组学揭示 FXR1 是卵巢癌 siRNA 治疗的可操作靶点

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、single-cell、transcriptomics
• 📝 描述：Contributors : Jasmine George ; Xiaolong Ma ; Ishaque Pulikkal Kadamberi ; Ajay Nair ; Sonam Mittal ; Elaheh Hashemi ; Sudhir Kumar ; Mona SinghSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusOvarian cancer is one of the leading causes of cancer-related mortality among women and remains exceptionally difficult to manage and treat effectively in the clinic. Fragile X-related protein 1 (FXR1) is significantly amplified and overexpressed in ovarian and various other cancers. We have shown that FXR1 acts as a key regulator of the stability and translation of multiple oncogenic mRNAs, establishing it as an excellent therapeutic target for ovarian cancer. Our Single-cell RNA sequencing (scRNA-seq) analysis demonstrates a complex involvement of FXR1 in cancer progression mainly due to its dual role attributed through its autonomous actions in tumor cells and the modulation of tumor microenvironment (TME). Recent advances in RNA interference (RNAi) therapies have enabled targeting previously undruggable genes. In this study, we developed a locked nucleic acid (LNA)-based small interfering RNA (siRNA) to target FXR1 for ovarian cancer therapy. Compared to native siRNA, siFXR1-LNA demonstrates resistance to RNase degradation, improved tumor tissue uptake, and robust inhibition of its target FXR1. siFXR1-LNA inhibited proteins essential for tumor growth and survival while increasing the levels of pro-apoptotic proteins. Importantly, the polyethylenimine-mediated delivery of siFXR1-LNA effectively reduced tumor growth and peritoneal metastasis in ovarian cancer models, without causing toxicity in both immunocompromised and immunocompetent mice. scRNA-seq further revealed that siFXR1-LNA treatment not only suppressed FXR1 in cancer cells but also disrupted translation mechanisms linked to oncogenesis. In TME, siFXR1-LNA diminished tumor cell proliferation, reduced tumor-promoting M2-like macrophages, increased tumor inhibitory T and NK cells and increased dendritic cells with anti-tumor characteristics. Given the autonomous role of FXR1 in tumor cells and TME for oncogenesis, targeting FXR1 with siFXR1-LNA presents a unique opportunity for treating ovarian cancer and other cancers express high levels of FXR1.
• 🔗 查看原文

2. ⭐ GSE308164 基于甲基化的三阴性乳腺癌DNA细胞解卷积揭示了预后免疫特征

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、immune、methylation
• 📝 描述：Contributors : Sarah Williams ; Ruth Pidsley ; Clare StirzakerSeries Type : Methylation profiling by genome tiling arrayOrganism : Homo sapiensIn triple negative breast cancer (TNBC), immune infiltration is now recognised as playing an important role in prognosis. DNA methylation, due to its cell-type specificity, offers a promising approach for quantifying immune cell abundance as a biomarker for risk stratification. Here, we used EpiDISH, a DNA methylation-based cellular deconvolution method, to estimate immune cell proportions from genome-wide methylation data across three independent cohorts, including TNBC patients. We show that increased immune cell percentage in TNBC patients specifically, was associated with longer disease-specific survival, highlighting the potential of DNA methylation-based estimates of cell composition for prognosis in TNBC.
• 🔗 查看原文

3. ⭐ GSE307573 有益的环境通过表观遗传调控促进免疫韧性[scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune、scRNA、epigenetic
• 📝 描述：Contributors : Theodoros Kapellos ; Guilherme Dragunas ; Yuexin Chen ; Herbert Schiller ; Zeynep Ertrüz ; Ali Önder YildirimSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusEnvironmental factors are often detrimental; however, certain environments enhance immune resilience. Notably, children raised on traditional farms show reduced allergies and asthma prevalence. Here, we investigated how a beneficial environment, using farm dust (FD) extract, influenced lung immune function in OVA-induced allergic inflammation. FD-exposure reduced allergic lung inflammation and increased monocyte-derived macrophage (MDM) recruitment. scRNA-seq revealed that FD-exposed MDMs had altered gene expression, including dampened Ccl8 and MHCII expression, impairing eosinophil recruitment and antigen presentation. RNA-seq and ATAC-seq confirmed FD-induced epigenetic reprogramming ex-vivo, on bone marrow-derived macrophages. This modulation, seen in both human and murine cells, relied on HDAC activity sustained by PPARγ signaling. These findings suggest that beneficial environmental exposures can reprogram immune cells and may offer a novel strategy for asthma prevention.
• 🔗 查看原文

4. GSE287046 肠道限制性LXR激动剂的特性及其在改善实验性短肠综合征肝损伤中的应用

• ✍️ 作者：未知作者
• 🏷️ 关键词：gut、regex:gut(-?microbiome)?
• 📝 描述：Contributors : Ayoung Kim ; Lingaiah Maram ; Hannah M Phelps ; Jichang Han ; Rachel L Mintz ; Brad W Warner ; Bahaa Elgendy ; Gwendalyn J RandolphSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusShort bowel syndrome (SBS) results from the surgical removal of extensive portions of the small intestine and is associated with high morbidity, including intestinal failure-associated liver disease (IFALD). We aim to identify effective, targeted therapies to combat IFALD while promoting small intestinal remodeling that optimizes intestinal health and nutrient absorption. Following previous findings that an LXR agonist administered orally suppresses liver injury in a mouse model of SBS, we sought application of a gut-restricted LXR agonist to avoid potential for systemic activation of LXR. We synthesized and characterized WUSTL0717 as a potential gut-restricted hydrophobic derivative of the well-known LXR agonist GW3965and tested its ability to improve outcomes in a mouse model of SBS. Pharmacokinetic analysis in mice revealed overwhelming intestinal retention of WUSTL0717. The compound activated a panoply of LXR target genes, including Abca1, in the small intestine but not the liver. It also increased ileal transcript levels of Apoa1 that encodes the core protein of high-density lipoprotein (HDL) and raised HDL levels in plasma. WUSTL0717 was efficacious in protecting against IFALD. Additionally, WUSTL0717 improved nutrient absorption after small intestinal resection and promoted restoration of body weight. These data identify the LXR agonist WUSTL0717 as a gut-restricted drug that may provide therapeutic benefits for treating SBS-associated IFALD while avoiding unwanted effects of systemic LXR agonists.
• 🔗 查看原文

5. GSE303006 通过单细胞四组学测序解析基因调控图谱

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing、single-cell
• 📝 描述：Contributors : Yujie Chen ; Zhiyuan LiuSeries Type : OtherOrganism : Mus musculusEnrichment libraries and Hi-C libraries were processed using identical scripts. Initially, different read types were demultiplexed based on identification sequences in the R2 read. For RNA data, we first removed reads containing no poly-A sequence following GAT5-RT primer sequence. We then aligned Read 1 to the GRCm38 reference genome using STAR. Duplicates were removed based on UMIs with UMI-tools. RNA count matrix was generated by FeatureCounts with parameters “-O -M –fraction”. We used RNAsnpSplit for phasing of allele- specific RNA counts.For HiC data, reads were mapped to the GRCm38 reference genome with BWA-mem2 in “5SP” mode. Contacts and 3D genome structures were generated with Hickit software using default parameters. To remove potential contamination from RNA reads, we cleaned contacts between two exons from the same transcript, which accounted for ~0.04% of all contacts. For quality control of reconstructed 3D genome structures, five replicates were generated with random seeds, and median RMSD for each combination of 3 replicates was calculated. The first replicate in the combination with the minimum median RMSD value (if < 1.5) was used for downstream analysis. 3D proximity and 3D distance maps were generated as previously described with custom codes. For accessibility reads and histone modification reads, R2 reads, which represent Tn5 insertion sites, were aligned using BWA-mem2 with default parameters. Afterward, a custom Python script was employed to remove PCR duplicates, generating single-cell signal fragment files. For haplotype phasing, fragments were first assigned to a haplotype using SNP information from the R2 read. If the haplotype could not be determined from R2, SNP information from the R1 read was then utilized. All reads were mapped to the mm10 reference genome. All these processing steps were organized and implemented using Snakemake, and are available at https://github.com/skelviper/CHARM.
• 🔗 查看原文

6. GSE308681 有益的环境通过表观遗传调控促进免疫韧性

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune、epigenetic
• 📝 描述：Contributors : Markus Klotz ; Guilherme Dragunas ; Sirui Chen ; Deepesh Dhakad ; Thomas M Conlon ; Ali Önder YildirimSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusEnvironmental factors are often detrimental; however, certain environments enhance immune resilience. Notably, children raised on traditional farms show reduced allergies and asthma prevalence. Here, we investigated how a beneficial environment, using farm dust (FD) extract, influenced lung immune function in OVA-induced allergic inflammation. FD-exposure reduced allergic lung inflammation and increased monocyte-derived macrophage (MDM) recruitment. scRNA-seq revealed that FD-exposed MDMs had altered gene expression, including dampened Ccl8 and MHCII expression, impairing eosinophil recruitment and antigen presentation. RNA-seq and ATAC-seq confirmed FD-induced epigenetic reprogramming ex-vivo, on bone marrow-derived macrophages. This modulation, seen in both human and murine cells, relied on HDAC activity sustained by PPARγ signaling. These findings suggest that beneficial environmental exposures can reprogram immune cells and may offer a novel strategy for asthma prevention.
• 🔗 查看原文

7. GSE312362 S100A7表达降低与皮肤衰老过程中分化、自噬和衰老相关程序的改变有关

• ✍️ 作者：未知作者
• 🏷️ 关键词：aging
• 📝 描述：Contributors : Ge Peng ; Fumihiro Hattori ; Hideoki Ogawa ; Ko Okumura ; François NiyonsabaSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTo investigate the role S100A7, a skin-derived antimicrotial peptide (AMP) in skin aging, we knockdowned S100A7 in normal human keratinocytes, which induced senescence markers, impaired autophagy, and partially recapitulated aging-associated transcriptional changes. Conversely, supplementation with physiological levels of S100A7 restored autophagic flux and attenuated senescence in D-galactose–induced aging models. These findings identify S100A7 as a molecular link between epidermal differentiation, autophagy, and cellular senescence, establishing an AMP–autophagy axis in skin aging.
• 🔗 查看原文

8. GSE309070 FBXO3介导的DUSP9泛素化重编程MAPK信号通路以根除酪氨酸激酶抑制剂耐药的CML干细胞

• ✍️ 作者：未知作者
• 🏷️ 关键词：kinase
• 📝 描述：Contributors : Xudong Li ; Shiyu Zuo ; Yongping Song ; Zhilei Bian ; Wei LiSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensDiscovering new therapeutic targets to overcome tyrosine kinase inhibitors (TKIs) resistance and clear leukemic stem cells (LSCs) is an urgent clinical need for chronic myeloid leukemia (CML) treatment. In the present study, we report that the F-box protein 3 (FBXO3) is upregulated in CD34+ CML stem cells from patients with TKI treatment failure and is regulated by BCR-ABL. Single-cell RNA sequencing (scRNA-seq) analysis indicated that FBXO3+ HSCs from CML patients have significant LSC signatures. Genetic depletion of FBXO3 significantly increased apoptosis and decreased proliferation of both imatinib-sensitive/resistant CML cell lines and CML stem cells in vitro and in vivo, with minimal effects on normal CD34+ HSCs. Mechanistically, FBXO3 interacts with DUSP9 and mediates its ubiquitination. DUSP9 knockdown partially counteracts the elimination of CML stem cells mediated by FBXO3 depleting in vitro and in vivo. RNA-seq results indicates that FBXO3-mediated ubiquitination of DUSP9 activates MAPK signaling pathway in CML cells. Moreover, FBXO3 inhibitor alone or in combination with imatinib significantly clear CML stem cells and overcome TKI resistance in murine and human CML, with minimal effects on normal hematopoiesis. Overall, our findings uncover novel roles of FBXO3 in CML progression and provide a rationale for combining FBXO3 inhibitors with TKIs to induce durable elimination of CML-LSCs.
• 🔗 查看原文

9. GSE313855 毛叶苕子绿肥通过功能较弱的GA20ox等位基因赋予的抗倒伏能力，提高了高产日本水稻品种的产量和籽粒外观品质

• ✍️ 作者：未知作者
• 🏷️ 关键词：resistance
• 📝 描述：Contributors : Hirofumi Fukuda ; Toshihiro Sakamoto ; Akari Fukuda ; Daisuke OgawaSeries Type : Expression profiling by high throughput sequencingOrganism : Oryza sativaGreen manure is widely advocated as a sustainable alternative to chemical fertilizers in crop systems, yet the mechanisms underlying its yield benefits remain unclear. Moreover, vigorous vegetative growth under green manure can elevate lodging risk, undermining yield and harvest efficiency. Here, we describe mechanisms by which hairy vetch–based green manure enhances yield and evaluate the practical value of deploying functionally weak alleles of gibberellin 20-oxidase (GA20ox) in this management context. We conducted field comparisons of green manure and conventional chemical fertilization to evaluate effects on rice productivity, grain appearance quality, and canopy physiology. Green manure significantly increased grain yield and grain appearance quality in the leading Japanese cultivar ‘Koshihikari’, accompanied by higher lodging. By contrast, high-yielding cultivars homozygous for a single-copy GA20ox1 allele and/or a non-functional GA20ox2 allele maintained superior lodging resistance under green manure treatment while improving yield and grain appearance quality, indicating an effective combination of its treatment and genotypes. Physiologically, green manure increased chlorophyll index during vegetative growth and at the reproductive stage, and nitrogen (N) concentration on the whole plant. Furthermore, green manure increased flag-leaf width and tiller number; these canopy changes were associated with reduced panicle temperature at the ripening stage. Green manure treatment induced upregulation of OsNADH-GOGAT2, a known gene associated with increased N loading to grains, and more grain storage proteins, providing a positive link to improved grain appearance quality. Collectively, this study demonstrates that integrating hairy vetch with functionally weak GA20ox alleles can enhance productivity and grain appearance quality while mitigating lodging risk. This sheds light on the importance of aligning green-manure treatment with targeted allelic selection to stabilize performance across intensive-farming systems and reduce chemical fertilizer dependency.
• 🔗 查看原文

10. GSE302464 AtNUDT11介导的dpCoA-RNA-seq定义了表观转录组dpCoA加帽RNA

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq
• 📝 描述：Series Type : Expression profiling by high throughput sequencingOrganism : Arabidopsis thalianaThis SuperSeries is composed of the SubSeries listed below.
• 🔗 查看原文

💡 该来源还有 4 条内容，详见 文末

详细内容（全部1条）

1. 科学家发现一种“主调节器”，或可逆转大脑衰老

• ✍️ 作者：未知作者
• 🏷️ 关键词：aging
• 📝 描述：Researchers have identified OTULIN, an immune-regulating enzyme, as a key trigger of tau buildup in the brain. When OTULIN was disabled, tau vanished from neurons and brain cells remained healthy. The findings challenge long-held assumptions about tau’s necessity and highlight a promising new path for fighting Alzheimer’s and brain aging. Scientists now believe OTULIN may act as a master switch for inflammation and age-related brain decline.
• 🔗 查看原文

• GSE300923 TRMT6 通过翻译调控多方面减轻 DSS 诱导结肠炎的易感性和进展 [RNA-seq]
• GSE294327 PLETHORA3/7 转录因子塑造黄瓜茎的结构 [RNA-Seq]
• GSE287449 靶向瓜氨酸化使 p53 与非经典位点结合 [ChIP-seq]
• GSE273414 MRTFA-SRF驱动的基因表达通过控制癌细胞中细胞质Ca2+和K+水平来促进细胞刚性