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1. ⭐ GSE332850 Xenium空间转录组学揭示TGFBRIIDN-Armored GPC3-CAR-T细胞在肝细胞癌患者中的作用机制

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Series Type : OtherOrganism : Homo sapiensThe GPC3-specific TGFBRII dominant-negative (DN) armored CAR-T cell therapy demonstrated promising clinical efficacy in phase I trials for advanced hepatocellular carcinoma (HCC). To investigate the spatial mechanisms of tumor response and resistance, we performed Xenium in situ spatial transcriptomic analysis on 18 samples from 13 patients of longitudinally collected FFPE tumor biopsies, enabling single-cell resolution mapping of tumor-immune interactions throughout the treatment course.
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2. ⭐ GSE319733 卵巢癌的肿瘤引流淋巴结缺乏生发中心，但含有与肿瘤内B细胞克隆相关的肿瘤反应性记忆B细胞

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、cancer、lymph、regex:lymph(o|atic)?
• 📝 描述：Contributors : Nachum Nathan ; Philipp Paparoditis ; Avital Sarusi-Portuguez ; Liat Stoler-Barak ; Hannah M Horn ; Roei Mazor ; Adva Levy-Barda ; Oded Raban ; Ram Eitan ; Ziv ShulmanSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensThe presence of B cells in tumors is correlated with a positive prognosis in several types of cancers, including high-grade serous ovarian cancer (HGSOC). These cells give rise to plasma cells (PCs) that originate from germinal centers (GCs) and secrete tumor-reactive antibodies. GCs also give rise to memory B cells (MBCs); yet, it is unknown if tumor-reactive MBCs form in cancer patients. Single-cell RNA-seq revealed that retroperitoneal lymph nodes (LNs) located near the tumor, host primarily class-switched resting MBCs. Immunoglobulin sequencing, clonal analysis, and generation of monoclonal antibodies demonstrated that these MBCs carried tumor-reactive antibodies, some of which bind MMP14, an enzyme abundantly expressed by HGSOC tumors. Although tumor-associated retroperitoneal LNs did not exhibit an active immune response, tumor binding of the MBCs derived from these LNs was dependent on somatic hypermutations (SHM), suggesting that they originated from a previous GC reaction. Different and overlapping types of MBC subpopulations were detected in the primary tumor and associated patient-matched LNs, some of which show clonal relationships between the two sites. Thus, our study extends our understanding of the anti-tumor memory response by revealing an inter-organ link between tumor-reactive MBC clones in ovarian cancer patients, which could potentially be manipulated in ovarian cancer patients.
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3. ⭐ GSE293119 整合阿尔茨海默病 GWAS、3D 基因组学和单细胞 CRISPRi 非编码筛选，揭示了小胶质细胞增强子中 TSPAN14 调控的致病变异。[RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer、RNA-seq、single-cell、genomics
• 📝 描述：Contributors : Natalia Tulina ; Alessandra ChesiSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensWhile GWAS have been successful in providing variant-to-trait associations for human complex diseases, functional dissection of the discovered loci has lagged behind. Here, we describe a variant-to-gene (V2G) mapping effort for Alzheimer’s disease (AD) to implicate causal variants and effector genes from the most recent AD GWAS meta-analyses (101 loci). We leveraged our genomics datasets comprising high-resolution promoter Capture C, ATAC-seq, and RNA-seq from brain-relevant cell types to fine-map AD GWAS variants, identifying 89 candidate causal SNPs and 69 effector genes. We then designed a single-cell CRISPRi screen to perturb candidate regulatory regions (n=74) and assess the transcriptional response in the human microglial cell line, HMC3. Our screen across ~97,000 cells identified 19 regulatory regions and 19 effector genes. We then elected to functionally dissect our top hit, the TSPAN14 locus, and we show that an intronic region containing AD-associated SNPs rs7080009, rs1870138, and rs1870137 is a microglia-specific enhancer, with the AD risk haplotype increasing its activity. CRISPR precise genomic deletion of this region decreases TSPAN14 expression, alters specific cellular pathways including cell adhesion, and decreases secreted levels of pro-inflammatory cytokines IL-6 and IL-8, which are known biomarkers of aging and AD. Our work provides a systematic framework to map GWAS signals to their effector genes for AD and other brain-related disorders, and provides robust leads to follow up with in-depth functional investigations.
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4. ⭐ GSE293118 阿尔茨海默病全基因组关联研究、3D基因组学和单细胞CRISPRi非编码筛选的整合表明，小胶质细胞增强子中存在调控TSPAN14的致病变异。[scRNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer、single-cell、scRNA、genomics
• 📝 描述：Contributors : Shannon Laub ; Alessandra ChesiSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensWhile GWAS have been successful in providing variant-to-trait associations for human complex diseases, functional dissection of the discovered loci has lagged behind. Here, we describe a variant-to-gene (V2G) mapping effort for Alzheimer’s disease (AD) to implicate causal variants and effector genes from the most recent AD GWAS meta-analyses (101 loci). We leveraged our genomics datasets comprising high-resolution promoter Capture C, ATAC-seq, and RNA-seq from brain-relevant cell types to fine-map AD GWAS variants, identifying 89 candidate causal SNPs and 69 effector genes. We then designed a single-cell CRISPRi screen to perturb candidate regulatory regions (n=74) and assess the transcriptional response in the human microglial cell line, HMC3. Our screen across ~97,000 cells identified 19 regulatory regions and 19 effector genes. We then elected to functionally dissect our top hit, the TSPAN14 locus, and we show that an intronic region containing AD-associated SNPs rs7080009, rs1870138, and rs1870137 is a microglia-specific enhancer, with the AD risk haplotype increasing its activity. CRISPR precise genomic deletion of this region decreases TSPAN14 expression, alters specific cellular pathways including cell adhesion, and decreases secreted levels of pro-inflammatory cytokines IL-6 and IL-8, which are known biomarkers of aging and AD. Our work provides a systematic framework to map GWAS signals to their effector genes for AD and other brain-related disorders, and provides robust leads to follow up with in-depth functional investigations.
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5. ⭐ GSE301554 氟维司群对乳腺癌细胞中雌激素受体驱动的染色质动力学的影响表明染色质开放与组蛋白乙酰化之间存在脱节 [ATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、ATAC-seq、histone
• 📝 描述：Contributors : Céline Barlier ; Mathias Simplicien ; Elsa Moreau ; Celia Fontana ; Aurelia Delherme ; Vincent Piras ; Gaylor Boulay ; Isabel PaivaSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensBackground: Epigenetic dysregulations are linked to various diseases, including cancer. Among them, breast cancer is the second leading cause of cancer-related deaths in women with 50% of mortalities attributable to estrogen receptor-positive (ER+) tumors. Endocrine therapies targeting the Estrogen Receptor (ER) such as Tamoxifen, Fulvestrant and Aromatase inhibitors, are widely used in the clinic. Among these therapeutic agents, Fulvestrant has been shown to fully antagonize ER activity, primarily through the rapid degradation and elimination of ER from target tissues. However, recent findings indicate that ER, when engaged with Fulvestrant, retains the ability to translocate to the nucleus and bind DNA whereas appearing transcriptionally inert. Results: In this study we aimed to further investigate the effects of Fulvestrant and Estradiol, an ER natural ligand, on ER cistrome, chromatin accessibility, and H3K27ac genome-wide patterns in an ER+ breast cancer cell line. Using the innovative CUT&Tag technology, we first confirmed that both Fulvestrant and Estradiol promote ER binding to DNA. Our findings revealed that Estradiol not only enhances chromatin accessibility but also increases H3K27ac levels at ER binding sites. In contrast, while Fulvestrant does not significantly alter chromatin accessibility, it can induce increases in H3K27ac levels at a subset of ER binding sites. Our observations suggest that Fulvestrant may modulate breast cancer transcriptional landscape by impacting H3K27ac dynamics, even in the absence of changes in chromatin accessibility. Conclusions: This study provides new insights on the mechanistic impact of Fulvestrant on Estrogen Receptor activity and their potential implications on target gene expression, particularly highlighting a novel putative role of H3K27ac dynamics in these processes.
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6. ⭐ GSE319641 RNA-Seq 分析了 NeoTRIP 试验中入组的乳腺癌患者治疗前和治疗中肿瘤样本。

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、cancer、RNA-seq
• 📝 描述：Contributors : Luca Gianni ; Giuseppe Viale ; Giampaolo Bianchini ; Matteo DugoSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTriple-negative breast cancer (TNBC) is immunogenic, but only a subset of patients benefits from neoadjuvant immune checkpoint inhibitors (ICIs) combined with chemotherapy. Predictive biomarkers to guide patient selection and treatment adaptation are lacking. In the NeoTRIPaPDL1 (NeoTRIP) Phase III trial, 280 high-risk TNBC patients were randomized to neoadjuvant carboplatin plus nab-paclitaxel (CT, n=142) or the same regimen with atezolizumab (CT/A, n=138). Tumor biopsies were collected at baseline and on the first day of the second cycle (D1C2). Longitudinal transcriptome sequencing and analyses of selected gene signatures were performed, including hallmark, ferroptosis-related, and immune cell type–specific signatures. Treatment-induced gene expression changes and association with pathological complete response were investigated.
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7. GSE310291 氟维司群对乳腺癌细胞中雌激素受体驱动的染色质动力学的影响 [RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、RNA-seq
• 📝 描述：Contributors : Céline Barlier ; Mathias Simplicien ; Ana Hermoso ; Anais Pourrat ; Elsa Moreau ; Celia Fontana ; Aurelia Delherme ; Natalie Daluege ; Gurpreet Bharaj ; Alexander Vogt ; Vincent Piras ; Coralie Hoareau-Aveilla ; Gaylor Boulay ; Isabel PaivaSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBackground: Epigenetic dysregulations are linked to various diseases, including cancer. Among them, breast cancer is the second leading cause of cancer-related deaths in women with 50% of mortalities attributable to estrogen receptor-positive (ER+) tumors. Endocrine therapies targeting the ER such as Tamoxifen, Fulvestrant (FULV) and Aromatase inhibitors, are widely used in the clinic. Among these therapeutic agents, FULV has been shown to fully antagonize ER activity, primarily through the rapid degradation and elimination of ER from target tissues. However, recent findings indicate that ER, when engaged with FULV, retains the ability to translocate to the nucleus and bind DNA whereas appearing transcriptionally inert. Results: In this study, we aimed to further investigate the effects of FULV and Estradiol (E2), the natural ER ligand, on ER cistrome, chromatin accessibility, gene transcription, and H3K27ac genome-wide patterns in ER+ breast cancer cell lines. Using the innovative CUT&Tag technology, we first confirmed that both FULV and E2 promote ER binding to DNA. Our findings revealed that E2 not only enhances chromatin accessibility and gene expression but also increases H3K27ac levels at ER binding sites. In contrast, FULV does not significantly alter chromatin accessibility or transcription but is not completely inert, as it induces increases in H3K27ac at a subset of ER binding sites. These observations indicate a decoupling between histone acetylation and transcriptional output under FULV treatment. Conclusions: This study provides new insights into the mechanistic impact of FULV on ER activity, highlighting its ability to modulate H3K27ac dynamics even in the absence of transcriptional changes. These findings underscore the complexity of ER signaling and suggest that FULV’s therapeutic effects may extend beyond simple antagonism of ER activity.
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8. GSE301553 氟维司群对乳腺癌细胞中雌激素受体驱动的染色质动力学的影响表明染色质开放与组蛋白乙酰化之间存在脱节 [CUT&Tag]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、histone
• 📝 描述：Contributors : Céline Barlier ; Mathias Simplicien ; Elsa Moreau ; Celia Fontana ; Aurelia Delherme ; Vincent Piras ; Gaylor Boulay ; Isabel PaivaSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensBackground: Epigenetic dysregulations are linked to various diseases, including cancer. Among them, breast cancer is the second leading cause of cancer-related deaths in women with 50% of mortalities attributable to estrogen receptor-positive (ER+) tumors. Endocrine therapies targeting the Estrogen Receptor (ER) such as Tamoxifen, Fulvestrant and Aromatase inhibitors, are widely used in the clinic. Among these therapeutic agents, Fulvestrant has been shown to fully antagonize ER activity, primarily through the rapid degradation and elimination of ER from target tissues. However, recent findings indicate that ER, when engaged with Fulvestrant, retains the ability to translocate to the nucleus and bind DNA whereas appearing transcriptionally inert. Results: In this study we aimed to further investigate the effects of Fulvestrant and Estradiol, an ER natural ligand, on ER cistrome, chromatin accessibility, and H3K27ac genome-wide patterns in an ER+ breast cancer cell line. Using the innovative CUT&Tag technology, we first confirmed that both Fulvestrant and Estradiol promote ER binding to DNA. Our findings revealed that Estradiol not only enhances chromatin accessibility but also increases H3K27ac levels at ER binding sites. In contrast, while Fulvestrant does not significantly alter chromatin accessibility, it can induce increases in H3K27ac levels at a subset of ER binding sites. Our observations suggest that Fulvestrant may modulate breast cancer transcriptional landscape by impacting H3K27ac dynamics, even in the absence of changes in chromatin accessibility. Conclusions: This study provides new insights on the mechanistic impact of Fulvestrant on Estrogen Receptor activity and their potential implications on target gene expression, particularly highlighting a novel putative role of H3K27ac dynamics in these processes.
• 🔗 查看原文

9. GSE298513 内皮细胞固有的 NOD2 信号通过效应 T 细胞和记忆 T 细胞的产生来调节肠道免疫反应。

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune、regex:intestin(e|al)
• 📝 描述：Contributors : Boyan K Tsankov ; Dana J PhilpottSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusCrohn’s disease (CD) involves aberrant intestinal T cell immunity, and genetic variants associated with disease development. Notably, mutations impairing NOD2 signaling represent the largest genetic risk factor for CD. Paradoxically, while variants in NOD2 are associated CD, its ligand, bacterial muramyl dipeptide (MDP) is a potent stimulator of innate immunity, long recognized as the minimal component required for the adjuvanticity of Complete Freund’s Adjuvant. This paradox underscores a critical gap in our understanding of how NOD2 coordinates the innate-adaptive immune crosstalk required to maintain intestinal homeostasis. Here, we show that NOD2 engagement by MDP drives T cell homing to the mesenteric lymph nodes during homeostasis and infection. This recruitment promotes antigen-specific effector and memory T cell accumulation in the ileal lamina propria, a process essential for effective recall responses and clearance of secondary infections. Mechanistically, this process requires endothelial-intrinsic NOD2 expression, which drives a specialized transcriptional program for leukocyte recruitment.
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10. GSE332761 单核细胞中的基线干扰素信号传导和注射部位抗体介导的先天激活影响mRNA疫苗的反应原性

• ✍️ 作者：未知作者
• 🏷️ 关键词：vaccine、antibody
• 📝 描述：Contributors : Natacha Madelon ; Gustavo A Ruiz Buendía ; Arnaud M DidierlaurentSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe local and systemic symptoms that follow vaccination -collectively referred to as reactogenicity- are common, yet the mechanisms underlying individual variability remain poorly understood. Through longitudinal immune profiling of vaccinated individuals and mechanistic studies in mice, we identified key immunological determinants of reactogenicity induced by mRNA vaccines. Systemic adverse events were associated with stronger interferon and pro-inflammatory responses following the second dose of COVID-19 vaccine, which were also correlated with the magnitude of the antigen-specific adaptive responses. This heightened inflammation occurred within 24 hours of vaccination and originated primarily from the injection site and was characterized by enhanced recruitment and activation of myeloid cells, particularly monocytes. Two mechanisms contributed to this response: (1) early interferon production by muscle T cells generated after the first dose and (2) FcγR-dependent chemokine induction by antigen-specific antibodies. Consistently, serum antibody levels prior to vaccination correlated positively with reactogenicity. In addition to this local amplification mechanism, variability in reactogenicity was influenced by the baseline immune state, as individuals with a pre-existing interferon-stimulated gene signature in monocytes, detectable at both transcriptomic and epigenetic levels, were more prone to systemic symptoms. Our findings reveal molecular and cellular mechanisms driving vaccine reactogenicity, providing a framework for the design of less reactogenic vaccines.
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1. 南加州大学科学家发现了一种隐藏的阿尔茨海默病诱因，并找到了一种可能的抑制方法。

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：USC researchers have identified potential new drug compounds that may reduce the brain inflammation linked to Alzheimer’s disease, especially in people with the high-risk APOE4 gene. The compounds target cPLA2, an enzyme that seems to fuel harmful inflammation while also being important for normal brain activity.
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• GSE332711 CD4/CD8 比值与 HIV 感染者疫苗诱导的免疫反应的结构重组相关
• GSE331406 肿瘤靶向降解SIRPα可重编程肿瘤相关巨噬细胞并恢复抗肿瘤免疫力
• GSE328769 研究发现，与阿尔茨海默病相关的早老素2 N141I 突变通过选择性下调高尔基体交换因子 Gbf1，损害神经元脂质稳态和线粒体动力学。
• GSE329967 高血糖进展过程中小鼠胰岛重塑的单细胞转录动态变化
• GSE332974 非酶促肝脏ABHD6与Akt-FoxO1轴相互作用以调节代谢健康
• GSE332879：野生型和LRRC8A基因敲除小鼠原代主动脉血管平滑肌细胞的批量RNA测序分析
• GSE319502 特发性复发性流产（RPL）中 METTL3_high 和 METTL3_Low 人类滋养层干细胞的全局转录组分析
• GSE330672 儿茶酚-O-甲基转移酶通过上调桥粒芯蛋白来减弱侵袭能力，并且与卵巢癌的良好预后相关
• GSE317340 循环死亡后捐献大鼠模型中心脏恢复及相应基因表达的性别差异
• GSE283075 乙酯对小鼠早期胚胎表观基因组的影响
• GSE282961 乙酯对小鼠早期胚胎转录组的影响