科研日报 2026-04-28

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📅 Daily Report - 2026-04-28

今日筛选出 14 条内容,来自 1 个来源

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🧬 数据前沿

今日焦点: 肠道微生物(多肠杆菌)增强肿瘤免疫治疗效果,以及靶向CDK12/ATR抑制剂在三阴性乳腺癌中的协同抗癌潜力。

主要方向

  • 肿瘤免疫与微生物组:探索肠道细菌对癌症免疫治疗(如抗PD-1/PD-L1)的调控机制,特别是在微卫星稳定结直肠癌中。
  • 癌症治疗新策略:开发靶向特定基因通路(如CDK12-ATR轴)的联合治疗方案,以克服三阴性乳腺癌的耐药性。
  • 衰老与疾病:通过生物信息学分析鉴定与颞下颌关节退变相关的衰老标志物基因。
  • 组织再生与修复:利用CD24+牙乳头细胞作为种子细胞,通过BMP2/SIRT1轴促进牙体牙髓再生。

技术亮点

  • 高通量测序技术:广泛应用于肿瘤、衰老、组织再生、药物反应等领域,包括单细胞RNA测序(scRNA-seq)和空间转录组学分析。
  • CRISPR-Cas9基因编辑:用于研究基因敲除对癌细胞转录组的影响。

📚 分类浏览

🧬 数据前沿 (14条)

详细内容(前10条)

1. GSE271663 肿瘤抑制性多种肠道细菌增强抗PD-1/PD-L1疗法在微卫星稳定型结直肠癌中的疗效

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:tumor、cancer
  • 📝 描述:Contributors : Xiaoting Su ; Mingsheng Zhang ; Zhou Li ; Fang LiSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Mus musculusGut microbiome significantly influences immunotherapy responses in colorectal cancer (CRC) treatment. While individual enterobacteria have been identified as enhancers of anti-PD-1/anti-PD-L1 therapy, the synergistic effects of multiple enterobacteria remain underexplored. To fill the gap, we introduced Tumor-Suppressing Multi-Enterobacteria (TSME), a consortium of nine beneficial intestinal probiotic strains, and investigated its impact on the anti-PD-1/anti-PD-L1 therapy for microsatellite stable (MSS) CRC. Using a tumor-bearing mouse model and genomic sequencing techniques, our research demonstrated that TSME significantly improved therapy efficacy by optimizing tumor immune microenvironment. Specifically, the addition of TSME notably increased CD8+ T infiltration, modulated cytokine profiles, and up-regulated crucial immune-related pathways, including TNF and JAK-STAT. Additionally, TSME altered intestinal microbial composition, enriching beneficial bacteria such as Akkermansia and Alistipes. These findings suggest that the well-engineered multi-enterobacteria could significantly enhance the effectiveness of immunotherapy for MSS CRC by synergistically modulating the immune and microbial landscapes.
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2. GSE315467 基于生物信息学的颞下颌关节退变衰老相关特征基因的鉴定

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:aging、bioinformatics
  • 📝 描述:Contributors : Xinyi Wang ; Ziyang Xia ; Minda Wang ; Yanzhang Zhou ; Ting Jiang ; Jingwen YangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusBackground: Temporomandibular joint (TMJ) degenerative diseases are increasingly affecting elderly populations, with aging being a significant risk factor driving the TMJ changes. This study aims to explore the shared characteristics between aging and TMJ degenerative diseases at the tissue level, and to identify aging-related signature genes in TMJ degenerations using bioinformatics approaches. Methods: Young (2 months of age, n=7) and aged (18 months of age, n=6) mice’s condyles were used to construct an aging dataset. Overlapping genes were selected from differentially expressed genes in the TMJOA dataset, aging dataset and mechanical stimulation dataset. Temporomandibular joint osteoarthritis-associated and aging-related differentially expressed genes (TMJOA-ARDEGs) were identified through Weighted gene co-expression network analysis. Functional enrichment analysis and Protein-Protein Interaction networks were employed. Machine learning was applied to select Hub temporomandibular joint osteoarthritis-associated and aging-related differentially expressed genes (Hub TMJOA-ARDEGs). An age-related TMJOA mouse model (18 months of age) was established and grouped based on the micro-CT and the modified Mankin scores. The expression changes of key Hub TMJOA-ARDEGs were verified by immunohistochemical staining. The Mann-Whitney U test was used in non-normally distributed data, presented as [median (interquartile range)]. Results: Fifty-two TMJOA-ARDEGs were identified, with functional enrichment analysis revealed that these genes participate in circadian rhythm and apoptosis. Eight Hub TMJOA-ARDEGs were identified, ANK1, MELTF, FERMT3, MDFI, CXCL14, EPHA3, SMOC2 and NR1D1. Based on the micro-CT, 12 TMJs of aged mice were divided into the TMJOA group (n=6) and the healthy group (n=6). Micro-CT revealed bone resorption in the TMJOA group compared to the healthy group, with a decrease in BV/TV (p<0.05) and an increase in Tb.Sp (p<0.05). The modified Mankin scores showed that the TMJOA group had a score of 5.61 (2.28), higher than the healthy group’s score of 0.83 (1.28), p<0.01. These results confirm the validity of the model grouping. Among the Hub TMJOA-ARDEGs, NR1D1 is a key gene involved in regulating circadian rhythm. In immunohistochemical staining, the expression level of NR1D1 …
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3. GSE328796 靶向细胞周期蛋白K-CDK12 与 ATR 抑制剂协同作用,通过限制 RPA 染色质加载来抑制三阴性乳腺癌 [ChIP-seq]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:cancer、ChIP-seq
  • 📝 描述:Contributors : Eun-Bee Choi ; Geoffrey I ShapiroSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensCyclin K-CDK12 inhibition has emerged as a promising therapeutic strategy to induce homologous recombination deficiency (HRD). However, clinical and genomic studies have not clearly linked CDK12 inactivation to HRD. Here, we demonstrate that cyclin K-CDK12 depletion drives a replication stress (RS)-associated vulnerability through RPA regulation. A DNA damage response-focused CRISPR screen identified DNA replication factors and ATR activators as top sensitizers to cyclin K degradation. Consistently, cyclin K-CDK12 depletion synergized with ATR inhibition in triple-negative breast cancer (TNBC) models. Cyclin K degradation reduces RPA chromatin loading and impairs ATR activation, compromising cellular tolerance to RS and increasing susceptibility to ATR inhibition. We show that CDK12-mediated phosphorylation of CDC5L is required for RPA chromatin loading and mediates resistance to combined cyclin K and ATR depletion. Our findings identify cyclin K-CDK12 as a critical regulator of RPA dynamics and support its inhibition as rational therapy for RS-high tumors, including TNBC.
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4. GSE309912 批量 RNA 测序结果显示,毒性脂质诱导的肝窦内皮细胞 ICAM1 表观遗传激活调节 MASH 中髓系驱动的纤维炎症反应。

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:RNA-seq、epigenetic
  • 📝 描述:Contributors : Qianqian Guo ; Nantawat Satthawiwat ; Akitoshi Sano ; Chady Meroueh ; Asma Hamdi ; Xin Dai ; Khaled Warasnhe ; Alexander M Washington ; Patrick P Starlinger ; Alex Krivonos ; Sheng Cao ; Enis Kostallari ; Johan W Jonker ; Bart van de Sluis ; Feda H Hamdan ; Samar H IbahimSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBackground: Liver sinusoidal endothelial cells (LSECs) acquire a proinflammatory phenotype in metabolic dysfunction-associated steatohepatitis (MASH), characterized by elevated adhesion molecules and inflammatory mediators—a process termed lipotoxic endotheliopathy. However, the molecular drivers of this transformation remain incompletely defined. Methods: We employed complementary models of lipotoxicity and MASH, including palmitate-treated primary human LSECs (in vitro), cultured precision-cut liver slices from normal human and mice liver with MASH-inducing media as well as MASH mice (ex vivo), and diet-induced MASH models (in vivo). Results: GeoMx digital spatial profiling of human MASH livers revealed enriched proinflammatory and fibrogenic signaling between LSECs and myeloid cells. Among the top upregulated genes and ligand-receptor pairs was ICAM1, whose expression correlated with disease severity and was increased in human MASH by immunostaining. ATAC-seq on primary mouse LSECs showed enhanced chromatin accessibility at the Icam1 promoter in MASH. Chromatin immunoprecipitation confirmed enrichment of the active epigenetic mark H3K27ac and BRD4 binding at the ICAM1 promoter in human LSECs under lipotoxic stress. Mechanistically, we identified the GSK3β/c-Jun/BRD4 axis as a key regulator of ICAM1 induction in LSECs. In vivo, ICAM1-neutralizing antibody or endothelial-specific epigenetic suppression reduced hepatic inflammation, injury, and fibrosis in MASH mice. Conclusion: ICAM1 is epigenetically upregulated in LSECs during lipotoxic stress and promotes myeloid cell recruitment in MASH. Targeting the epigenetic regulation of ICAM1 may offer a novel therapeutic strategy for treating human MASH.
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5. GSE305390 MGUS进展为骨髓瘤及治疗反应后基质和内皮细胞转录变化 [scRNA-seq]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:scRNA
  • 📝 描述:Contributors : Itziar Cenzano ; Felipe ProsperSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe role of the non-immune bone marrow microenvironment (BME) in the transition from monoclonal gammopathy of undetermined significance (MGUS) into clinically active multiple myeloma (MM) remains incompletely defined. To address this, we transcriptionally profiled endothelial cells (EC), mesenchymal stem cells (MSC), and MM cells at single-cell resolution from genetically engineered mouse models (BIc1 and MIc1) that recapitulate MGUS to MM progression. Our analysis of the BIc1 model revealed distinct transcriptional alterations in EC and MSC, uncovering stage-specific BME-PC interactions shaping disease progression. Interestingly, we identified an interferon (IFN)-related myeloma signature in both EC and MSC that was reversed after treatment with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd).
  • 🔗 查看原文

6. GSE305389 MGUS进展为骨髓瘤及治疗反应后基质和内皮细胞转录变化 [RNA-Seq]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:RNA-seq
  • 📝 描述:Contributors : Itziar Cenzano ; Felipe ProsperSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThe role of the non-immune bone marrow microenvironment (BME) in the transition from monoclonal gammopathy of undetermined significance (MGUS) into clinically active multiple myeloma (MM) remains incompletely defined. To address this, we transcriptionally profiled endothelial cells (EC), mesenchymal stem cells (MSC), and MM cells at single-cell resolution from genetically engineered mouse models (BIc1 and MIc1) that recapitulate MGUS to MM progression. Our analysis of the BIc1 model revealed distinct transcriptional alterations in EC and MSC, uncovering stage-specific BME-PC interactions shaping disease progression. Interestingly, we identified an interferon (IFN)-related myeloma signature in both EC and MSC that was reversed after treatment with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd).
  • 🔗 查看原文

7. GSE303610 两种不同的 SWI/SNF 复合物指导弓形虫中染色质相关的转录程序 [RNA-Seq]

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:RNA-seq
  • 📝 描述:Contributors : Dominic Schwarz ; Sebastian LouridoSeries Type : Expression profiling by high throughput sequencingOrganism : Toxoplasma gondiiChromatin remodeling complexes dynamically modify DNA accessibility to mediate changes in gene expression during eukaryotic cell cycle progression, developmental transitions, and environmental adaptation. Higher eukaryotes have multiple remodeler subtypes based on the incorporation of different ATPases; however, the coordination and functional specificity of these diverse complexes is not well understood. Apicomplexan parasites such as Toxoplasma gondii have a limited set of chromatin remodelers offering a divergent setting in which to explore the function of homologous complexes. These parasites have selectively retained the Myb domain–containing proteins with homology to chromatin-associated regulators like SNF2h and SWI3. Here, a comprehensive analysis of the Myb protein family in Toxoplasma defines the composition of two SWI3 complexes with mutually exclusive ATPase homologous—TgSNF2a and TgSNF2b. Integrating transcriptomics with a custom chromatin-profiling strategy, we show that TgSNF2a is essential for the timely transcription of genes, while TgSNF2b ensures global transcriptional competency and fidelity throughout the cell cycle and developmental transitions. Cell cycle–resolved chromatin profiling conclusively shows the shift from TgSNF2b to TgSNF2a occupancy when regulated genes transition from being poised to being actively transcribed. Our findings demonstrate that TgSNF2a and TgSNF2b perform distinct yet interdependent regulatory roles shaped by their chromatin context. This work uncovers ancestral principles of chromatin regulation and offers new insight into the functional diversification of SWI/SNF complexes across eukaryotes.
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8. GSE303466 CD24+ 人牙乳头细胞作为转化种子细胞,通过 BMP2/SIRT1 代谢轴促进牙本质-牙髓再生

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:metabolic
  • 📝 描述:Contributors : Cheng Liang ; Zhi Liu ; Jie Li ; Cong Han ; Yu Gao ; Bohuai Zhou ; Qiuyu Chen ; Fei Bi ; Weimin Wu ; Tiantian Hu ; Jingyi Zhang ; Ding Bai ; Yiping Chen ; Weidong Tian ; Tian ChenSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiens ; Mus musculusRegeneration of the dentin-pulp complex is a central goal in dental tissue engineering, essential for restoring both structural integrity and biological function of damaged teeth. However, the inherent heterogeneity of dental stem cells limits our understanding of lineage-specific subsets critical for efficient odontogenesis and regenerative outcomes. Here, we identify a distinct subpopulation of human dental papilla cells (hDPCs) marked by CD24 expression. CD24⁺ hDPCs exhibit robust odontogenic differentiation capacity, preferential localization to odontoblast-generating regions during tooth development, and accumulation beneath reparative dentin in carious teeth. Functionally, CD24⁺ hDPCs drive coordinated regeneration of well-vascularized pulp and structurally integrated dentin tissues in both ectopic murine and preclinical in situ minipig models, significantly outperforming conventional dental pulp stem cells. Mechanistically, we delineate a BMP2-driven metabolic axis in which elevated BMP signaling sustains SIRT1 expression and promotes mitochondrial metabolism. Inhibition of BMP signaling disrupts this axis, activating WNT signaling, reducing SIRT1 expression, compromising antioxidant and autophagic responses, and consequently diminishing odontogenic capacity. Furthermore, BMP signaling in CD24⁺ hDPCs induces VEGF expression, enhancing endothelial cell recruitment and neovascularization via paracrine effects. CD24 also acts as a downstream marker of odontogenic BMP signaling, reflecting BMP pathway activation and correlating with odontogenic potential, although it does not directly mediate differentiation. Together, our findings characterize CD24⁺ hDPCs as a regeneration-competent subpopulation that integrates mitochondrial metabolism and signaling crosstalk to enable coordinated dentin and pulp regeneration, representing a translationally relevant cell source for dental tissue engineering.
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9. GSE328990 RNA-seq 分析雌性小鼠下丘脑揭示膜启动的雌激素受体α信号传导的影响

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:RNA-seq
  • 📝 描述:Contributors : Yiwen Jiang ; Karin Horkeby ; Petra Henning ; Karin H Nilsson ; Jianyao Wu ; Lei Li ; Sofia Movérare-Skrtic ; Claes Ohlsson ; Marie K LagerquistSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusMembrane-initiated estrogen receptor alpha (mERα) signaling plays an important role in bone metabolism, but its contribution in the brain remains unclear. In this study, we performed RNA sequencing of hypothalamic tissue from 16-week-old female mice with selective inactivation of mERα signaling in POMC neurons (POMC-C451Af/f) and wild-type littermate controls. Total RNA was isolated from hypothalamus, and samples were pooled (two animals per sample) resulting in four biological replicates per genotype. Libraries were prepared using poly(A) selection and sequenced on an Illumina NovaSeq 6000 platform with paired-end 150 bp reads. Transcript abundance was quantified using Salmon and summarized to gene-level counts. Differential expression analysis was performed using DESeq2. This dataset provides insight into transcriptional changes associated with disrupted mERα signaling in hypothalamic neurons.
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10. GSE328853 化疗后 APOE3 和 APOE4 小鼠的空间转录组分析

  • ✍️ 作者:未知作者
  • 🏷️ 关键词:spatial
  • 📝 描述:Contributors : Olga Rodriguez ; Naazneen Khan ; Adrian Oblak ; Jeff Dage ; Chris AlbaneseSeries Type : OtherOrganism : Mus musculusSpatial transcriptomic profiling of APOE4 mice post-chemotherapy compared with APOE3 knock-in mice to assess genotype-specific regional gene expression changes.
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💡 该来源还有 4 条内容,详见 文末

📊 关键词统计

关键词出现次数
RNA-seq4
cancer4
scRNA1
metabolic1
tumor1
aging1
bioinformatics1
spatial1
ChIP-seq1
epigenetic1
transcriptome1
macrophage1

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