科研日报 2026-03-19

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📅 Daily Report - 2026-03-19

今日筛选出 36 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: 空间转录组学技术在癌症(如鳞状细胞癌、胶质母细胞瘤)和体内CRISPR筛选中的应用取得进展,实现了对细胞微环境和基因功能的精细解析。

主要方向

  • 空间组学解析癌症微环境:利用空间转录组学研究鳞状细胞癌、胶质母细胞瘤等癌症的细胞异质性和微环境特征。
  • 体内基因编辑与功能筛选:开发和应用空间解析的体内CRISPR筛选技术,用于大规模基因功能研究。
  • 免疫细胞与疾病:探索性别对自然杀伤细胞介导的胰腺癌免疫的影响,以及CAR-NK细胞免疫疗法的开发。
  • 表观遗传调控机制:研究表观遗传和增强子网络重塑在脂肪细胞分化、HSPCs发育及认知障碍/阿尔茨海默病中的作用。

技术亮点

  • 空间解析的体内CRISPR筛选:整合了基因编辑与空间转录组学,实现对体内基因功能的高分辨率研究。
  • 新型CAR-NK细胞免疫疗法:开发一步法敲入CAR-NK细胞,为大规模、现成的免疫疗法生产提供可能。

🧪 博客更新

今日焦点: AI赋能单细胞RNA测序数据分析,助力发现隐藏生物学洞见;新型阿尔茨海默病药物(lecanemab)作用机制首次揭示,通过激活大脑免疫细胞发挥作用。

主要方向

  • 利用AI代理(AI agents)自主挖掘单细胞RNA测序数据中的新生物学规律。
  • 评估半监督与无监督方法在单细胞RNA测序数据整合中的性能差异。
  • 阐明阿尔茨海默病药物lecanemab通过激活大脑免疫细胞发挥疗效的具体机制。

技术亮点

  • AI驱动的单细胞RNA测序数据分析,实现自主发现生物学洞见。
  • 揭示lecanemab激活大脑免疫细胞的具体抗体片段(F fragment)。

📚 分类浏览

🧬 数据前沿 (33条)

详细内容(前10条)

1.GSE321832 不同组织鳞状细胞癌的空间转录组学

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:carcinoma、spatial、spatial transcriptomics、transcriptomics
  • 📝 描述:Contributors : Amaya Virós ; Kevin Harrington ; Malin Pederson ; Ben O’Leary ; Antonio RullanSeries Type : OtherOrganism : Homo sapiensWe performed spatial transcriptomics on primary squamous cell carcinomas (SCC) from the head and neck, lung and skin to characterise tissue-specific stromal and epithelial cell interactions
  • 🔗 查看原文

2.GSE319277 通过 Perturb-DBiT 进行空间分辨全景体内 CRISPR 筛选 [空间转录组学]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:spatial、spatially、spatial transcriptomics、transcriptomics
  • 📝 描述:Contributors : Alev E Baysoy ; Xiaolong Tian ; Paul Renauer ; Feifei Zhang ; Sidi Chen ; Rong FanSeries Type : OtherOrganism : Mus musculusSpatially resolved in vivo CRISPR screening integrates gene editing with spatial transcriptomics to examine how genetic perturbations alter gene expression within native tissue environments. However, current methods are mostly for small perturbation panels and the detection of a subset of protein-coding RNAs. We present Perturb-DBiT, a versatile approach for the simultaneous co-sequencing of spatial total RNA whole-transcriptome and single-guide RNAs (sgRNAs), base-by-base, on the same tissue section. This method enables unbiased discovery of how genetic perturbations influence RNA regulation, cellular dynamics, and tissue architecture in situ. Applying Perturb-DBiT to a human cancer metastatic colonization model, we mapped large panels of sgRNAs across tumor colonies in multiple consecutive tissue sections alongside their corresponding total RNA transcriptomes, providing insights into how perturbations affect long non-coding RNA (lncRNA) co-variation, microRNA–mRNA interactions, and distinct amino acid-specific tRNA alterations linked to tumor migration and growth. By integrating transcriptional pseudotime trajectories, we further observed the impact of perturbations on clonal dynamics and cooperation. In an immune-competent syngeneic mouse model, Perturb-DBiT enabled investigation of genetic perturbations within the tumor immune microenvironment, potentially revealing distinct and synergistic effects on immune infiltration and suppression. Perturb-DBiT provides a spatially resolved comprehensive view of how genetic knockouts influence diverse molecular and cellular responses including small and large RNA regulation, tumor proliferation, migration, metastasis, and immune interactions, offering a panoramic perspective on perturbation responses in complex tissues.­­­­
  • 🔗 查看原文

3.GSE324268:来自脑切片上培养的患者来源胶质母细胞瘤类器官和原发性胶质母细胞瘤样本的Xenium单细胞空间转录组学分析

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:spatial、spatial transcriptomics、transcriptomics
  • 📝 描述:Contributors : Michael Hölzel ; Frank A Giordano ; Julian P Layer ; Matthias Schneider ; Anna-Laura Potthoff ; Barbara E PreglerSeries Type : OtherOrganism : Homo sapiensGlioblastoma shows marked spatial heterogeneity and hypoxia-associated signaling. Here, we performed probe-based Xenium single-cell spatial transcriptomics on a primary human glioblastoma sample and on a patient-derived glioblastoma organoid cultured on a brain slice. The aim was to assess the in situ single-cell expression of hypoxia-related genes, with a particular focus on VEGFA and CXCL12. These datasets provide spatially resolved transcriptomic information to study hypoxic niches and tumor microenvironmental interactions in glioblastoma.
  • 🔗 查看原文

4. GSE315398 空间和批量转录组学分析揭示了基于疾病特征的存档皮肤卡波西肉瘤病变中不同的基因表达谱(NCounter 数据)

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:spatial、transcriptomics
  • 📝 描述:Contributors : Ramya Ramaswami ; Edmund Culley ; Baman Afsari ; Quashawn Chadwick ; Xiaolin WuSeries Type : Expression profiling by arrayOrganism : Homo sapiensTargeted transcriptomics assay of immuno-oncology genes using NanoString PanCancer IO 360 panel (770 gene) was carried out with archival skin Kaposi sarcoma samples.42 participants with HIV-associated KS with and without other KSHV-associated diseases (KICS, PEL and/or MCD) included
  • 🔗 查看原文

5. GSE309514 性别决定了自然杀伤细胞介导的抗胰腺癌免疫力。

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:cancer、immunity
  • 📝 描述:Contributors : Arlt Elise ; Bley Nadine ; Misiak DannySeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusPancreatic ductal adenocarcinoma ranks among the most aggressive malignancies and exhibits a higher prevalence and poorer prognosis in male patients. Natural killer cells play a critical role in tumor immunosurveillance by directly recognizing and eliminating tumor cells. It is well established that females generally mount stronger immune responses than males. The present study aims to answer the question of whether sex has an influence on the NK cell-mediated anti-tumor function in PDAC. To validate our in vitro findings in a physiological context, we employed a syngeneic allograft mouse model.
  • 🔗 查看原文

6. GSE305881 宿主对细菌的反应诱导小鼠肠类器官模型中肠内分泌细胞谱系的转变

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:bacteria、regex:bacter(ia|ial|ium)
  • 📝 描述:Contributors : Marry Nissan ; Stephen E GirardinSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe host response to commensal and pathogenic bacteria has been extensively characterized using human cancer cell line models, but remains poorly defined in primary intestinal cellular systems. Recent evidence has demonstrated that mice lacking the Nod-like receptor (NLR) protein NLRC4 are susceptible to S. flexneri infection and thus represent a new model to study the mechanistic aspects of S. flexneri -host interaction. Using ileal organoids from wild type (WT) and Nlrc4-/- mice, we first confirmed that NLRC4 was required for the restriction of intracellular S. flexneri growth. Surprisingly, NLRC4 further mediated the detection of bacteria-free S. flexneri supernatants, suggesting that ileal organoids sample proteins from the type three secretion system (T3SS) to mediate a preemptive pyroptotic response to pathogens independently from invasion. Moreover, both invasive and non-invasive S. flexneri were found within Nlrc4-/- ileal organoids, suggesting that murine intestinal epithelial cells (IECs) may be capable of bacterial uptake. Transcriptional analysis further revealed that S. flexneri infection in Nlrc4-/- organoids resulted in the downregulation of inflammatory signaling, associated with an enrichment for markers of the enteroendocrine cell lineage (EEC). This finding was recapitulated in organoids in contact with a non-pathogenic strain of S. flexneri, suggesting that EEC expansion depended on either bacterial contact or pickup. Together, our results reveal unexpected characteristics of host-bacterial interaction in primary murine IECs, which may shape the response to the microbiota and enteric pathogens at the intestinal mucosal surface
  • 🔗 查看原文

7. GSE299464 开发用于大规模现货生产的一步敲入 CAR-NK 免疫疗法 [RNA-Seq]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:regex:immuno(logy|therapy|suppression)、RNA-seq
  • 📝 描述:Series Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensChimeric antigen receptor (CAR)-engineered natural killer (NK) cells offer a promising immunotherapy for various malignancies. However, their efficacy in treating solid tumors is often compromised by the immunosuppressive tumor microenvironment (TME), where TGF-β1 plays a key role in inhibiting NK cell function. To address this challenge, our study focused on developing a simple, one-step process for generating CAR-NK cells, termed “one-step CAR-NK”, by simultaneously knocking out TGFβR2 and knocking in a CAR gene into human primary NK cells. We first demonstrated that knocking out TGFβR2 using CRISPR-Cas9 enhanced NK-mediated cancer killing abilities with upregulated CD107a expression when co-cultured with AsPC-1 cells. Additionally, we optimized the donor DNA by inserting a binding motif for dexamethasone, which encodes a CAR targeting mesothelin (MSLN) as a tumor antigen, to integrate into the TGFβR2 locus. Using electroporation, the Cas9 protein/gRNA complex combined with CAR donor DNA significantly increased the knock-in efficacy, resulting in potent cancer killing against solid tumors. Furthermore, we explored a two-step CAR-NK manufacturing process, using AAV to deliver DNA instead of naked DNA. This method also showed high KI efficacy and robust cancer-killing capabilities. As with the one-step process, the supplement of dexamethasone further improved NK functions in two-step CAR-NK cells. Thus, our one-step CAR-NK platform, particularly in the presence of dexamethasone, holds promise as off-the-shelf therapeutics with a simple and scalable manufacturing process for treating solid tumors.
  • 🔗 查看原文

8. GSE299308 开发用于大规模现货生产的一步敲入 CAR-NK 免疫疗法 [ATAC-seq]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:regex:immuno(logy|therapy|suppression)、ATAC-seq
  • 📝 描述:Series Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensChimeric antigen receptor (CAR)-engineered natural killer (NK) cells offer a promising immunotherapy for various malignancies. However, their efficacy in treating solid tumors is often compromised by the immunosuppressive tumor microenvironment (TME), where TGF-β1 plays a key role in inhibiting NK cell function. To address this challenge, our study focused on developing a simple, one-step process for generating CAR-NK cells, termed “one-step CAR-NK”, by simultaneously knocking out TGFβR2 and knocking in a CAR gene into human primary NK cells. We first demonstrated that knocking out TGFβR2 using CRISPR-Cas9 enhanced NK-mediated cancer killing abilities with upregulated CD107a expression when co-cultured with AsPC-1 cells. Additionally, we optimized the donor DNA by inserting a binding motif for dexamethasone, which encodes a CAR targeting mesothelin (MSLN) as a tumor antigen, to integrate into the TGFβR2 locus. Using electroporation, the Cas9 protein/gRNA complex combined with CAR donor DNA significantly increased the knock-in efficacy, resulting in potent cancer killing against solid tumors. Furthermore, we explored a two-step CAR-NK manufacturing process, using AAV to deliver DNA instead of naked DNA. This method also showed high KI efficacy and robust cancer-killing capabilities. As with the one-step process, the supplement of dexamethasone further improved NK functions in two-step CAR-NK cells. Thus, our one-step CAR-NK platform, particularly in the presence of dexamethasone, holds promise as off-the-shelf therapeutics with a simple and scalable manufacturing process for treating solid tumors.
  • 🔗 查看原文

9. GSE293133 RNA-seq - 表观遗传和增强子网络的多模态重塑塑造了米色脂肪细胞的转录图谱

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:RNA-seq、epigenetic
  • 📝 描述:Contributors : Sarah Hazell Pickering ; Mohamed Abdelhalim ; Natalia M Galigniana ; Anita L Sørensen ; Manuela Zucknick ; Philippe Collas ; Nolwenn BriandSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensEpigenetic regulation is a key determinant of adipocyte fate and function, conferring phenotypic plasticity to adipose tissue in response to metabolic and thermal challenges. To understand the spatiotemporal regulation of chromatin during the establishment of a beige thermogenic adipocyte phenotype, we analyzed the transcriptomic, epigenetic, and enhancer connectome dynamics during white and beige adipogenesis. Using a machine learning approach, we find that the white-specific transcriptional program is associated with promoter modulations of H3K2ac levels and chromatin accessibility. In contrast, beige-specific mitochondrial gene expression correlates with promoter changes in H3K4me3 levels. Adipocyte beiging is also mediated by a remodeling of the 3D genome involving the recruitment of short range enhancers targeting fatty acid oxidation and thermogenic genes. These increased promoter-enhancer contacts correlate with increased chromatin opening at sites enriched for C/EBP transcription factor motifs. We notably identify the C/EBP transcription factor NFIL3 as differentially bound between white and beige adipocytes at enhancers regulating PDK4, a key metabolic switch promoting fatty acid oxidation. Our results highlight a multimodal, pathway-specific regulation of the transcriptional program underlying the beige adipocyte phenotype.
  • 🔗 查看原文

10. GSE287757 体外扩增的造血干细胞及其T细胞祖细胞后代的转录和表观遗传程序

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:T cell、epigenetic
  • 📝 描述:Contributors : Brendan MacNabb ; Boyoung Shin ; Samantha Chang ; Ellen V RothenbergSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusHematopoietic stem and progenitor cells (HSPCs) in the bone marrow are the ultimate sources of all hematopoietic lineage cells, including T cells. However, gene expression programs and chromatin dynamics that guide the bone marrow progenitor cells to enter the T-development programs are not fully understood due to limited cell numbers and population heterogeneity. By exploiting the in vitro HSPC expansion approach, which effectively expands HSPCs with high T cell potentials, we monitored the gene expression programs and chromatin accessibility changes underlying the transition from the bone marrow progenitor stages to early T cell development stages. Notably, expanded HSPCs displayed strikingly similar chromatin accessibility profiles with early-stage T cell progenitors, representing their shared hematopoietic chromatin landscapes. However, a select set of genomic regions and target genes were specifically regulated as cells first received the strong Notch signaling and engaged with T-development conditions. These events included a robust chromatin opening and transcriptional activation of the T cell receptor (TCR)-C beta locus. In addition, well-known stem and progenitor-associated transcription factors were sharply repressed, often concerted with broad chromatin accessibility losses at those loci. These gene regulation targets were not an artifact of in vitro expanded HSPC-derived pro-T cells. The progeny of expanded HSPCs and freshly isolated HSPCs share the same T-lineage developmental trajectory at the single-cell transcriptome level, and their gene expression programs were highly similar. However, expanded HSPC-derived pro-T cells showed temporal differences in early T-development speed and progressed through pre-commitment stages slowly. From cytokine and chemokine screening, we found that a brief Flt3L pre-treatment during the 4-5 days of the expansion period could moderately accelerate the T-development kinetics of expanded HSPCs. Thus, we compared the chromatin accessibility programs, H3K27ac and H3K27me3 histone marks, and gene expression programs upon Flt3L treatment. Although chromatin state and transcriptional features were mostly not altered by Flt3L treatment at the bulk population levels, scRNA-seq results showed that a set of activation and stress-response g…
  • 🔗 查看原文

💡 该来源还有 23 条内容,详见 文末

🧪 博客更新 (3条)

详细内容(全部3条)

1. CellVoyager——人工智能代理拓展了从单细胞RNA测序数据中获得的洞见

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:sequencing
  • 📝 描述:AI driven analysis of RNA sequencing data enables autonomous discovery of new biological insights, helping researchers uncover hidden patterns in complex single cell datasets…
  • 🔗 查看原文

2. 评估用于单细胞RNA测序整合的半监督方法

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:sequencing
  • 📝 描述:RNA sequencing integration methods show variable performance, with semi supervised approaches sensitive to imperfect labels and unsupervised methods often providing more reliable results in real world datasets…
  • 🔗 查看原文

3. 科学家终于揭示了这种阿尔茨海默病药物的真正作用机制。

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:Alzheimer
  • 📝 描述:A key Alzheimer’s drug has finally revealed its secret. Researchers discovered that lecanemab works by activating the brain’s immune cells—but only through a specific part of the antibody called the Fc fragment. This piece acts like a trigger, prompting microglia to clear harmful amyloid plaques. The finding could reshape how future Alzheimer’s therapies are designed.
  • 🔗 查看原文

📊 关键词统计

关键词出现次数
RNA-seq6
spatial4
transcriptomics4
sequencing3
ATAC-seq3
spatial transcriptomics3
immunity3
epigenetic3
ChIP-seq2
carcinoma2
cancer2
regex:bacter(iaial
regex:immuno(logytherapy
genome2
Alzheimer2
spatially2
macrophage2
tumor2
metabolism1
bacteria1

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🧬 数据前沿 其他内容 (23条)

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