科研日报 2026-04-08

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📅 Daily Report - 2026-04-08

今日筛选出 46 条内容,来自 2 个来源

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🤖 今日AI智能总结

🧬 数据前沿

今日焦点: 空间转录组学在肿瘤微环境(胰腺癌、心脏免疫炎症)及细胞内mRNA定位研究中取得进展。

主要方向

  • 肿瘤免疫治疗与基因组修复:研究低剂量放疗与免疫疗法联合应用对免疫排斥型肿瘤中CD8+ T细胞功能的增强作用,尤其关注同源重组修复缺陷的肿瘤。
  • 微生物组与宿主免疫:探索肠道菌群对宿主营养免疫和抵抗病原体(如鲍曼不动杆菌肺炎)的影响。
  • 基因编辑与细胞工程:利用CRISPR-Cas9技术进行多功能细胞工程,并应用于增强T细胞疗效和 digit 修复。

技术亮点

  • 空间转录组学:应用于肿瘤微环境分析(胰腺癌、心脏免疫抑制)和亚细胞mRNA定位。
  • 多组学整合:结合单细胞RNA-seq、bulk RNA-seq、ChIP-seq等技术,全面解析肿瘤、微生物及发育过程中的分子机制。

🧪 博客更新

今日焦点: RNA测序技术在绝对定量和FFPE样本分析方面实现突破,为疾病机制研究和药物开发提供新视角。

主要方向

  • 利用RNA测序精确量化基因表达,实现跨实验和跨实验室的标准化比较。
  • 通过RNA测序解析克罗恩病肠道纤维化的免疫细胞和内皮细胞相互作用,发现新的治疗靶点。
  • 运用新型条形码技术,实现对固定石蜡包埋(FFPE)样本的全转录组单细胞RNA测序分析。

技术亮点

  • 标准化参考物校准RNA测序,实现基因表达的绝对定量。
  • FFPE兼容的单细胞全转录组测序技术,解锁存档样本的分析潜力。

📚 分类浏览

🧬 数据前沿 (43条)

详细内容(前10条)

1.GSE327056 利用10x Genomics Visium平台对人胰腺导管腺癌进行空间转录组分析

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:10x、spatial、Visium、genomics
  • 📝 描述:Contributors : Zhangyong Ren ; Bing Pan ; Fangfei Wang ; Shaocheng Lyu ; Jialei Zhai ; Xiumei Hu ; Zhe Liu ; Lixin Li ; Ren Lang ; Qiang He ; Xin ZhaoSeries Type : OtherOrganism : Homo sapiensIn this study, we performed spatial transcriptomics (ST) to investigate the gene expression features across one normal pancreatic tissue, PC tissue, adjacent tumor tissue, and tumor stroma using 10x Genomics Visium spatial gene expression platform. We generated high-quality spatial gene expression profiles combined with histomorphological information, aiming to reveal the spatial heterogeneity of pancreatic cancer microenvironment and identify spatially restricted gene signatures associated with tumor progression. Sequencing was performed on Illumina NovaSeq 6000 platform, and data processing was conducted using SpaceRanger software with hg38 reference genome. The results revealed that KRT13+FABP5+ malignant cell subpopulation had keratinization characteristics in the tumor tissue. Fibroblasts from adjacent tumor tissue exhibited a tumor-inhibiting role such as “B-cell activation” and “positive regulation of leukocyte activation.” The FGG+CRP+ inflammatory cancer-associated fibroblasts replaced the islets in tumor stroma. During PC progression, the damage to pancreatic structure and function was heavier in the pancreatic exocrine (AMYA2+PRSS1+) than in the endocrine (INS+GCG+). Our results revealed the spatial heterogeneity of dynamic changes and highlighted the significance of impaired exocrine function in PC.
  • 🔗 查看原文

2.GSE295600 对免疫排斥性肿瘤患者联合应用低剂量辐射和免疫疗法可有效增强同源重组修复缺陷肿瘤中 CD8+ T 细胞的功能 [scRNA-seq]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:immune、T cell、regex:immuno(logy|therapy|suppression)、scRNA
  • 📝 描述:Contributors : Nicolas Rayroux ; Maria Ochoa-de-Olza ; Fernanda Herrera ; Denarda Dangaj-LanitiSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensImmune-checkpoint blockade (ICB) has shown significant efficacy across various tumor types. However, tumors with low intraepithelial T-cell infiltration, often referred to as “cold” tumors, are expected to yield poor responsiveness to ICB. We investigated the potential of LDRT to enhance immune-checkpoint blockade (ICB) responses in 25 patients with multimetastatic immune-excluded solid tumors through a multi-cohort phase I clinical trial (RACIN). Primary endpoint was to determine the safety and tolerability of the combination of a backbone treatment, comprising nivolumab, ipilimumab, aspirin/celecoxib, and low-dose cyclophosphamide in association with escalated LDRT. Secondary endpoints included among others disease control rate (DCR) and overall survival (OS). Exploratory endpoints included biomarkers and molecular correlates of response. The combination treatment showed a manageable safety profile, with Grade 3 or higher adverse events in 12% to 21% of patients across cohorts. The overall disease control rate (CR + PR + SD) was 41.6%. Progression free survival across all cohorts was 2.1 months (95% C.I.: 1.8 – 4.2 months), with the highest PFS observed in cohort 1 which received 0.5 Gy (5.7 months, (95% C.I.: 1.9 - 11.3 months). Median overall survival was 14.0 months (95% CI: 8.5–24.6 months), with one patient with ovarian cancer still maintaining a complete response at three years follow-up. Site-paired tumour biopsies collected for each patient at baseline and after LDRT +/- Cy enabled the comprehensive characterization of the dynamics of their excluded/desert tumour microenvironments (TME) at the single cell level. Response to LDRT and ICB was associated with DNA damage and repair responsiveness and the presence of detectable intratumoral PD1+CD8+ tumour infiltrating lymphocytes (TILs) at baseline. Our data revealed that LDRT amplified CD8+ TIL functionality in responding patients offering mechanistic insights on how LDRT improves ICB effectiveness. In contrast, we observed a radiosensitivity of TILs in tumours of non-responders. Detailed single cell immune profiling before LDRT also highlighted a lack of key immune stimulatory myeloid cells that can therefore limit ICB efficacy in excluded tumors. Collectively, this study represents the most comprehensive profiling of l…
  • 🔗 查看原文

3.GSE295599 对免疫排斥性肿瘤患者联合应用低剂量辐射和免疫疗法可有效增强同源重组修复缺陷肿瘤中 CD8+ T 细胞的功能 [bulk RNA-seq]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:immune、T cell、regex:immuno(logy|therapy|suppression)、RNA-seq
  • 📝 描述:Contributors : Nicolas Rayroux ; Maria Ochoa-de-Olza ; Fernanda Herrera ; Denarda D LanitiSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensImmune-checkpoint blockade (ICB) has shown significant efficacy across various tumor types. However, tumors with low intraepithelial T-cell infiltration, often referred to as “cold” tumors, are expected to yield poor responsiveness to ICB. We investigated the potential of LDRT to enhance immune-checkpoint blockade (ICB) responses in 25 patients with multimetastatic immune-excluded solid tumors through a multi-cohort phase I clinical trial (RACIN). Primary endpoint was to determine the safety and tolerability of the combination of a backbone treatment, comprising nivolumab, ipilimumab, aspirin/celecoxib, and low-dose cyclophosphamide in association with escalated LDRT. Secondary endpoints included among others disease control rate (DCR) and overall survival (OS). Exploratory endpoints included biomarkers and molecular correlates of response. The combination treatment showed a manageable safety profile, with Grade 3 or higher adverse events in 12% to 21% of patients across cohorts. The overall disease control rate (CR + PR + SD) was 41.6%. Progression free survival across all cohorts was 2.1 months (95% C.I.: 1.8 – 4.2 months), with the highest PFS observed in cohort 1 which received 0.5 Gy (5.7 months, (95% C.I.: 1.9 - 11.3 months). Median overall survival was 14.0 months (95% CI: 8.5–24.6 months), with one patient with ovarian cancer still maintaining a complete response at three years follow-up. Site-paired tumour biopsies collected for each patient at baseline and after LDRT +/- Cy enabled the comprehensive characterization of the dynamics of their excluded/desert tumour microenvironments (TME) at the single cell level. Response to LDRT and ICB was associated with DNA damage and repair responsiveness and the presence of detectable intratumoral PD1+CD8+ tumour infiltrating lymphocytes (TILs) at baseline. Our data revealed that LDRT amplified CD8+ TIL functionality in responding patients offering mechanistic insights on how LDRT improves ICB effectiveness. In contrast, we observed a radiosensitivity of TILs in tumours of non-responders. Detailed single cell immune profiling before LDRT also highlighted a lack of key immune stimulatory myeloid cells that can therefore limit ICB efficacy in excluded tumors. Collectively, this study represents the most comprehensive profiling of longit…
  • 🔗 查看原文

4.GSE327129 利用空间转录组学解析组织间亚细胞mRNA定位模式

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:spatial、spatial transcriptomics、transcriptomics
  • 📝 描述:Contributors : Roy Novoselsky ; Ofra Golani ; Tal Barkai ; Merav Kedmi ; Inna Goliand ; Shalev ItzkovitzSeries Type : OtherOrganism : Mus musculusSubcellular RNA localization, including nuclear retention and apical-basal compartmentalization in polarized epithelia plays a central role in post-transcriptional regulation. However, methods for high-throughput mapping of mRNA localization within intact tissue sections remain limited. Here, we apply high-resolution spatial transcriptomics to systematically resolve intracellular mRNA localization across diverse mammalian tissues. We introduce a computational approach that leverages image-derived features to extract subcellular information from spatial data and quantifies transcript localization patterns. Using this framework, we map apical-basal mRNA localization and nuclear retention in gastrointestinal epithelia and in liver hepatocytes. Our analyses reveal conserved and tissue-specific localization signatures that can be readily obtained from standard high-definition spatial transcriptomics experiments. This approach broadens the scope of spatial transcriptomics by enabling routine investigation of intracellular RNA distributions in both healthy and diseased tissues.
  • 🔗 查看原文

5.GSE313334 肠道菌群影响营养免疫和对鲍曼不动杆菌肺炎的抵抗力

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:immunity、resistance、regex:intestin(e|al)
  • 📝 描述:Contributors : Erin R Green ; Nicholas M Negretti ; Nicolas G Shealy ; Tess Brunner ; Felipe A Moser ; Sydney L Drury ; Kacie A Traina ; Valeria M Reyes Ruiz ; Tzushan S Yang ; Eric G Pamer ; Mariana X Byndloss ; Raf van de Plas ; Joseph P Zackular ; Samuel H Light ; Jennifer M Sucre ; Eric P SkaarSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusBroad-spectrum antibiotics are frequently administered prophylactically to intensive care unit patients as part of empiric care. This treatment has been associated with subsequent infections by the emerging nosocomial pathogen Acinetobacter baumannii; however, the mechanisms underlying this association remain unclear. Here, we demonstrate in a murine model that prophylactic broad-spectrum antibiotic administration drives susceptibility to intranasal infections with A. baumannii, and that reconstitution of the intestinal microbiota by fecal microbiota transplant restores control of infection, implicating microbiota dysbiosis as a key driver of pulmonary disease. Using single-cell RNA sequencing, we determine that prophylaxis suppresses phagocyte effector functions in the lung, including nutritional immunity pathways that restrict pathogen access to essential nutrient metals. Depletion studies identify neutrophils and inflammatory monocytes as central mediators of microbiota-dependent protection, and infection of mice lacking nutritional immunity components lipocalin-2 or calprotectin abrogates the effects of prophylaxis, establishing a causal linkage between microbiota dysbiosis and impaired phagocyte-mediated nutritional immunity. Together, these findings provide a mechanism for the increased severity of A. baumannii pneumonia following antibiotic exposure and highlight the intestinal microbiota as a potential therapeutic target to prevent future nosocomial infections with this and other healthcare-associated pathogens.
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6.GSE326883 TLR9激动剂通过B细胞-CD2共刺激轴增强过继性T细胞疗法在癌症治疗中的疗效

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:cancer、T cell、B cell
  • 📝 描述:Contributors : Ayana Ruffin ; Chrystal PaulosSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAdoptive T cell transfer (ACT) therapy offers curative potential for some patients with cancer. Toll-like receptor (TLR) agonists improve the efficacy of ACT therapy, but the underlying mechanism of potency remains poorly understood. Here, we identify a previously unrecognized innate-adaptive circuit in which TLR9-activated B cells augment CD8 T cell fitness and antitumor activity through CD2-dependent costimulation. Among multiple TLR agonist tested, class B CpG uniquely programmed murine and human CD8⁺ T cells for superior effector differentiation, metabolic fitness and antitumor control. Disruption of CD2 signaling blunts the benefits of TLR9 agonism, including glycolytic capacity and tumor control. Independently, blocking CD86/CD80/CD28 or ICOS did not impair CpG conditioned CD8 T cell anti-tumor activity. Gain of function experiments revealed that CD2 stimulation recapitulated the effect of TLR9 agonism, bolstering the effector function of TIL and CAR T cells. Clinically, consistent with these findings, elevated CD2 expression in human tumors correlated with improved overall survival across multiple cancer cohorts, underscoring the importance of this signaling cue. Together, these data uncover a non-canonical B cell-CD2 costimulation axis through which TLR9 agonists potentiate ACT, revealing a targetable pathway to overcome resistance to cell therapy in solid tumors.
  • 🔗 查看原文

7.GSE326567 通过转录组分析解析长芒苋(Amaranthus palmeri S. Watson)对多种除草剂的代谢抗性

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:metabolic、resistance、transcriptome
  • 📝 描述:Contributors : Rishabh Singh ; Yaiphabi Kumam ; Mohit Mahey ; Eric Patterson ; Sanzhen Liu ; Sarah Lancaster ; Mithila JugulamSeries Type : Expression profiling by high throughput sequencingOrganism : Amaranthus palmeriMultiple herbicide resistance in Palmer amaranth (Amaranthus palmeri S. Watson) poses a serious threat to US crop production. A Palmer amaranth population (KCTR) from Kansas was found resistant to herbicides across six sites of action, including ALS-, PS II-, EPSPS-, PPO-, HPPD-inhibitors and synthetic auxins. Moreover, a predominance of metabolic resistance, possibly mediated by P450s or GSTs enzyme activity was reported in this population. This study aims to identify the specific genes involved in multiple herbicide metabolism in this Palmer amaranth population via transcriptome analysis. Vegetative clones were developed from three biological replicates of both resistant (KCTR/KCTR-G2) and susceptible (KSS) Palmer amaranth populations. Ten to 12 cm tall clones from each biological replicate were treated with labelled doses of chlorsulfuron, 2,4-D, atrazine, lactofen and mesotrione. Leaf samples were collected for RNA isolation at 6 hours after treatment with respective herbicides along with non-treated plants. Upon RNA sequencing, paired end reads generated were mapped to the Palmer amaranth transcriptome using HISAT2. Differential gene expression analysis revealed 414, 129, 529, 688 and 152 genes expressed differentially in resistant plants following chlorsulfuron, 2,4-D, atrazine, lactofen and mesotrione treatments, respectively. Isoforms of CYP72A219 or CYP704B1 and GST C-terminal were alternatively up-regulated expression across treatments. Transcripts for CYP72A219 and CYP704B1 show up-regulated expression of 3.4- to 6.6-fold and 5.9- to 12.4-fold in resistant plants as validated by qRT-PCR. Identification of genes involved in multiple herbicide metabolism in Palmer amaranth is crucial to predict the evolutionary course of herbicide resistance in weed species.
  • 🔗 查看原文

8.GSE302811 RNA测序分析了乳腺癌术后放疗或单纯手术后伤口渗出液中分离的单核免疫细胞。

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:cancer、immune、RNA-seq
  • 📝 描述:Contributors : Nikko Brix ; Benedek Dankó ; Martin SelmansbergerSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThis dataset comprises RNA-seq profiles from mononuclear immune cells purified from wound fluid of breast cancer patients who received intraoperative radiotherapy (IORT) or surgery only (control). Samples were collected on postoperative day 2 and processed for total RNA extraction and 3′-end mRNA sequencing. The study aims to characterize the transcriptional immune landscape in the early wound-healing phase following IORT.
  • 🔗 查看原文

9. GSE291273 胎盘特异性组蛋白 H3.4 促进生殖细胞发育和生殖适应性 [RNA-seq]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:RNA-seq、histone
  • 📝 描述:Contributors : Antoine H F.M. Peters ; Pavel A. KomarovSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusGenes involved in chromatin remodeling during sperm development are under strong evolutionary pressure to optimize reproductive fitness In mice, the histone H3.4 variant, encoded by the single copy H3f4 gene, is essential for spermatogenesis. H3.4 is highly expressed in spermatogonia and replaces progressively canonical H3 histones during spermatogonial expansion and differentiation. Phylogenetic analysis shows that H3f4 is specific to the placental lineage and originates from an ancestral H3.2 gene existing prior to the divergence of placental and marsupial mammals over 100 million years ago. Situated in a majorly truncated histone cluster, placental H3f4 orthologs show increased synonymous and non-synonymous substitution rates compared to analogous marsupial H3.2 genes. H3f4 carries four non-synonymous substitutions relative to H3.2 genes. To understand the impact of evolutionary sequence divergence on reproductive fitness, we reverted three of four non-synonymously substituted residues in H3f4 to those present in H3.1 (H3f4V24A, H3f4H42R, H3f4S98A) while leaving H3f4C96 intact which is identical to H3.1C96. When expressed from both alleles, neither single nor triple reversion of diverged residues affected spermatogenesis much. In contrast, hemizygous expression of the triply reverted H3f4H3.1 allele on a H3f4-deficiency background caused an >40% reduction in testis weight associated with death of pachytene spermatocytes, impaired differentiation of spermatids and aberrant expression of thousands of genes during spermatid elongation. Hemizygous expression of individual residue substitution alleles revealed that residues V24 and H42 of H3.4 promote spermatogenesis, while residue S98 is neutral. Together, our study shows that H3f4 has been subject to positive evolutionary selection, promoting male reproductive fitness.
  • 🔗 查看原文

10. GSE291272 胎盘特异性组蛋白 H3.4 促进生殖细胞发育和生殖适应性 [ChIP-seq]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:ChIP-seq、histone
  • 📝 描述:Contributors : Antoine H F.M. Peters ; Pavel A. KomarovSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusGenes involved in chromatin remodeling during sperm development are under strong evolutionary pressure to optimize reproductive fitness In mice, the histone H3.4 variant, encoded by the single copy H3f4 gene, is essential for spermatogenesis. H3.4 is highly expressed in spermatogonia and replaces progressively canonical H3 histones during spermatogonial expansion and differentiation. Phylogenetic analysis shows that H3f4 is specific to the placental lineage and originates from an ancestral H3.2 gene existing prior to the divergence of placental and marsupial mammals over 100 million years ago. Situated in a majorly truncated histone cluster, placental H3f4 orthologs show increased synonymous and non-synonymous substitution rates compared to analogous marsupial H3.2 genes. H3f4 carries four non-synonymous substitutions relative to H3.2 genes. To understand the impact of evolutionary sequence divergence on reproductive fitness, we reverted three of four non-synonymously substituted residues in H3f4 to those present in H3.1 (H3f4V24A, H3f4H42R, H3f4S98A) while leaving H3f4C96 intact which is identical to H3.1C96. When expressed from both alleles, neither single nor triple reversion of diverged residues affected spermatogenesis much. In contrast, hemizygous expression of the triply reverted H3f4H3.1 allele on a H3f4-deficiency background caused an >40% reduction in testis weight associated with death of pachytene spermatocytes, impaired differentiation of spermatids and aberrant expression of thousands of genes during spermatid elongation. Hemizygous expression of individual residue substitution alleles revealed that residues V24 and H42 of H3.4 promote spermatogenesis, while residue S98 is neutral. Together, our study shows that H3f4 has been subject to positive evolutionary selection, promoting male reproductive fitness.
  • 🔗 查看原文

💡 该来源还有 33 条内容,详见 文末

🧪 博客更新 (3条)

详细内容(全部3条)

1. RNA测序正朝着基因表达的绝对测量方向发展

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:sequencing
  • 📝 描述:RNA sequencing calibration using standardized references enables absolute quantification of gene expression, improving cross-study comparisons and reducing bias across experiments and laboratories…
  • 🔗 查看原文

2. 科学家利用RNA测序来识别克罗恩病肠道瘢痕的诱因

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:sequencing
  • 📝 描述:RNA sequencing reveals interactions between immune and endothelial cells that drive fibrosis in Crohn’s disease, identifying new pathways that could guide targeted therapies…
  • 🔗 查看原文

3. Parse Biosciences推出与FFPE兼容的条形码技术,用于全转录组单细胞分析

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:transcriptome
  • 📝 描述:Parse Biosciences enables RNA sequencing of FFPE samples at single cell resolution, unlocking archived tissues for whole transcriptome analysis and deeper insights into gene…
  • 🔗 查看原文

📊 关键词统计

关键词出现次数
immune9
RNA-seq8
sequencing6
transcriptome6
resistance4
T cell4
carcinoma4
cancer3
single-cell3
scRNA2
histone2
cardiac2
spatial2
regex:intestin(eal)
Neuronal2
metabolic2
regex:immuno(logytherapy
ChIP-seq1
spatial transcriptomics1
transcriptomics1

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🧬 数据前沿 其他内容 (33条)

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