科研日报 2026-07-21
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📅 Daily Report - 2026-07-21
今日筛选出 29 条内容,来自 1 个来源
🤖 今日AI智能总结
🧬 数据前沿
今日焦点: 空间转录组学揭示胆道闭锁疾病全程SOX-4信号通路作用;ZFP36L2在肠道再生和结直肠癌转移中的应激适应性可塑性调控机制被多维度解析。
主要方向:
- 疾病机制研究:胆道闭锁、急性髓系白血病、类风湿性关节炎、结直肠癌、肝纤维化、马立克氏病、本氏疟原虫感染。
- 细胞生物学:朗格汉斯细胞在皮肤损伤修复中的作用、T细胞发育、肝细胞对疟原虫的训练性免疫。
- 分子生物学:ZFP36L2在应激适应与疾病中的功能、RECQL4在DNA复制与基因组维持中的作用、长链全氟烷基物质对树突状细胞成熟的影响。
技术亮点:
- 空间转录组学:用于解析疾病在组织微环境中的细胞异质性。
- 多组学整合:结合全基因组DNA甲基化测序、ATAC-seq、SLAM-seq、HyperTRIBE、ActD-seq、scRNA-seq等技术,深入研究基因调控和细胞功能。
📚 分类浏览
🧬 数据前沿 (29条)
详细内容(前10条)
1. ⭐ 利用 PacBio HiFi 测序技术确定嗜酸热脂杆菌亚种 KCTC 1825 菌株的全基因组 DNA 甲基化基序(GSE338709)。
- ✍️ 作者:未知作者
- 🏷️ 关键词:sequencing、genome、methylation
- 📝 描述:Contributor : Jae-Yoon SungSeries Type : Methylation profiling by high throughput sequencingOrganism : Alicyclobacillus acidocaldarius subsp. acidocaldariusPacBio HiFi sequencing was used to characterize genome-wide DNA base modifications and methylation motifs in Alicyclobacillus acidocaldarius subsp. acidocaldarius strain KCTC 1825 (DSM 446). Base-modification kinetics were mapped to the complete genome assembly and analyzed for m6A and m4C signals. The processed dataset provides per-base modification calls, motif-associated calls, and motif summaries linked to the public genome assembly and SRA run.
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2. ⭐ GSE338525 空间转录组学研究支持 SOX-4 驱动的信号通路在胆道闭锁疾病进程中的作用
- ✍️ 作者:未知作者
- 🏷️ 关键词:spatial、spatial transcriptomics、transcriptomics
- 📝 描述:Contributors : Tallulah S Andrews ; Sarah A TaylorSeries Type : OtherOrganism : Homo sapiensBiliary atresia (BA) is a fibroinflammatory cholangiopathy of infancy that is the most common indication for pediatric liver transplantation. We aimed to define the molecular mechanisms responsible for differences in the rate of disease progression among children with BA. We performed spatial transcriptomics (ST) analysis on frozen liver tissue at transplant from 16 children: BA with survival with native liver (SNL) 2 years (BA2, n=4), non-BA cholestasis (n=4), and non-diseased donors (n=4). Transcriptional signatures were compared between patient groups by tissue region (scar, hepatocyte, cholangiocyte). Findings were validated in larger patient cohorts that included BA samples at diagnosis. ST analysis of BA1 patients showed the most aggressive disease phenotype, characterized by reduced hepatocyte zonation, low expression of homeostatic metabolic signatures, and increased scar heterogeneity enriched for pathways including extracellular matrix remodeling, interferon response, and leukocyte activation. Notably, genes involved in SOX4 hepatocyte-to-cholangiocyte reprogramming were most enriched in BA1 patients. Liver immunohistochemistry with in situ mRNA hybridization showed that BA patients at diagnosis had increased SOX4 quantification as compared to BA patients at transplant. Lastly, previously published liver bulk RNA-sequencing data demonstrated higher SOX4 gene-set expression in BA patients at diagnosis with SNL < 2 years. Children with BA and worse outcome exhibit increased SOX4 gene-set expression at diagnosis with greater loss of hepatocyte zonation and immune-driven scar heterogeneity at transplant. Further mechanistic studies are needed to determine whether SOX4-driven biliary reprogramming plays a maladaptive role in the reparative response to obstructive cholestasis in BA.
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3. ⭐ GSE336319 ZFP36L2 调控肠道再生和结直肠癌转移中的应激适应性可塑性(批量 RNA 测序)
- ✍️ 作者:未知作者
- 🏷️ 关键词:cancer、RNAseq、regex:intestin(e|al)
- 📝 描述:Contributors : Karuna Ganesh ; Qingwen Jiang ; Jura PintarSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBulk RNA sequencing was performed on MSK107Li patient-derived colorectal cancer (CRC) liver metastasis organoids to characterize transcriptional changes resulting from CRISPR-Cas9-mediated ZFP36L2 knockout during dedifferentiation. ZFP36L2 was disrupted using two independent sgRNAs; two validated knockout clones per sgRNA were pooled for sequencing, with control organoids serving as comparators. To assess dedifferentiation capacity, organoids were cultured in intestinal growth factor-free (IGFF) medium for 13 days to induce differentiation, then dissociated into single cells and passaged into HISC medium; samples were harvested on day 7 of dedifferentiation. Total RNA was extracted using the RNeasy Mini Kit (Qiagen) and submitted to Plasmidsaurus for 3′ end RNA-seq library preparation and sequencing. Libraries were generated using a 3′ end counting approach with unique molecular identifiers (UMIs) incorporated during cDNA synthesis. ZFP36L2 knockout organoids exhibited decreased ISC-associated gene signatures and increased expression of canonical and non-canonical differentiation programs, including osteoblast, squamous, and neuroendocrine lineages, relative to controls.
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4. GSE338812 疟原虫血液期诱导肝细胞产生训练免疫 - ATAC-seq
- ✍️ 作者:未知作者
- 🏷️ 关键词:immunity、ATAC-seq
- 📝 描述:Contributors : Elizabeth K Glennon ; Alexis KaushanskySeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusPlasmodium parasites, the causative agents of malaria, are transmitted at high levels in endemic areas and sequential infections are common. Using a mouse model of infection we discovered liver burden was suppressed in blood-stage experienced, compared to naïve, animals, independently of adaptive responses and inflammation. We observed greater chromatin accessibility of a subset of interferon stimulated genes in blood-stage experienced animals, and a rapid increase in transcription of these genes upon sporozoite challenge. Ex vivo stimulation of hepatocytes from blood-stage experienced mice also led to a rapid and elevated response upon treatment with an unrelated antigen, ctDNA. Taken together, these data are consistent with a model in which hepatocytes are reprogramed by blood stage Plasmodium infection to exhibit trained memory akin to what has been described in innate immune cells. The consequences of training of hepatocytes could be wide-reaching and might alter responses to diverse pathogens and other stimuli.
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5. GSE338808 朗格汉斯细胞的双谱系协同作用,在皮肤损伤后恢复免疫屏障(scRNA-seq)
- ✍️ 作者:未知作者
- 🏷️ 关键词:immune、scRNA
- 📝 描述:Contributors : Axel D Schmitter-Sánchez ; Sangbum ParkSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusLangerhans cells (LCs) are key immune sentinels of the epidermis. How this network reorganizes to safeguard epidermal immunity after injury has remained unclear. Here, we uncover a previously unrecognized two-lineage program of LC repopulation during wound repair. Classically, tissue-resident embryonically derived LCs (eLCs) migrate to lymph nodes in response to antigens. In contrast, we find that injury triggers nearby eLCs to migrate into wounds, providing immediate coverage. In parallel, circulating monocytes infiltrate the skin and differentiate into long-lived monocyte-derived LCs (mLCs) that integrate stably into the network. We identify the chemokine receptor CXCR2 as a novel regulator of eLC migration into wounds, distinct from the CXCR4/CCR7 pathways mediating LC egress to lymph nodes. Pharmacological inhibition of CXCR2 impairs directional eLC migration and is accompanied by increased mLC infiltration, preserving immune barrier density. These findings reveal a coordinated and flexible two-lineage repair program that ensures robust restoration of epidermal immunity.
- 🔗 查看原文
6. GSE336781 ZFP36L2 调控肠道再生和结直肠癌转移中的应激适应性可塑性
- ✍️ 作者:未知作者
- 🏷️ 关键词:cancer、regex:intestin(e|al)
- 📝 描述:Contributors : Karuna Ganesh ; Qingwen Jiang ; Jura Pintar ; Cyrus L Tam ; Britney ForsythSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensPhenotypic plasticity is a hallmark of cancer, yet the molecular switches required for cell fate reprogramming are poorly understood. During intestinal wound healing and colorectal cancer (CRC) metastasis, differentiated cells can dynamically dedifferentiate into an intestinal stem cell (ISC) state to drive epithelial regeneration and metastatic outgrowth. Here we show that the RNA-binding protein ZFP36L2, which is mutated in 5-10% of CRC, is a critical stress-responsive orchestrator of dynamic dedifferentiation into an LGR5+ ISC state. In mouse colon regeneration models, ZFP36L2 ablation inhibits dedifferentiation, ISC gene expression and function, and impairs intestinal regeneration. In human CRC, loss of ZFP36L2 function abrogates metastatic seeding and the outgrowth of LGR5+ canonical metastases, while promoting lineage plasticity and non-canonical differentiation into heterogeneous cell states. Mechanistically, we find that ZFP36L2 binds to stress-associated mRNAs containing AU-rich 3’ UTRs, inducing the formation of dynamic biomolecular condensates associated with mRNA degradation and termination of the stress response. Together, this work defines ZFP36L2 acts as a critical molecular switch coupling stress sensing with phenotypic plasticity, driving cellular dedifferentiation essential for re-establishing the ISC state during wound healing and metastasis. In ZFP36L2 deficient CRC, inability to re-enter the LGR5+ state during metastatic outgrowth drives non-canonical lineage plasticity, associated with poor clinical outcomes.This SuperSeries is composed of the SubSeries listed below.
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7. GSE336564 ZFP36L2 调控肠道再生和结直肠癌转移中的应激适应性可塑性(PDO scRNAseq)
- ✍️ 作者:未知作者
- 🏷️ 关键词:cancer、regex:intestin(e|al)
- 📝 描述:Contributors : Karuna Ganesh ; Qingwen Jiang ; Jura Pintar ; Britney ForsythSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensSingle-cell RNA sequencing (scRNA-seq) was performed on patient-derived primary colorectal cancer (CRC) organoids (OKG146P) to investigate the role of ZFP36L2 in regulating cell state plasticity during differentiation and dedifferentiation. Organoids expressing a doxycycline-inducible shRNA targeting ZFP36L2 (shZFP36L2) or a non-targeting control (shCtrl) were cultured with 2 μg/mL doxycycline and subjected to three conditions: (1) HISC medium for 7 days (baseline ISC state); (2) HISC for 7 days followed by intestinal growth factor-free (IGFF) medium for 7 days (differentiation); and (3) HISC for 7 days, IGFF for 7 days, then HISC for 7 days (dedifferentiation). Organoids were dissociated into single cells and multiplexed using TotalSeq hashtag antibodies (BioLegend). Viable (DAPI-negative) cells were FACS-sorted and pooled in equal numbers across conditions for library preparation using the Chromium Single Cell 3′ v3.1 platform (10x Genomics), targeting up to 10,000 cells per sample. Libraries were sequenced on an Illumina NovaSeq S4 (Read 1: 28 cycles; i7 index: 8 cycles; Read 2: 90 cycles). ZFP36L2 knockdown decreased the proportion of ISC-like cells across HISC and dedifferentiation conditions and impaired re-acquisition of the ISC state following dedifferentiation, with the greatest phenotypic divergence observed upon dedifferentiation.
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8. GSE336417 ZFP36L2 协调肠道再生和结直肠癌转移中的应激适应性可塑性 (SLAMseq)
- ✍️ 作者:未知作者
- 🏷️ 关键词:cancer、regex:intestin(e|al)
- 📝 描述:Contributors : Karuna Ganesh ; Qingwen Jiang ; Jura Pintar ; Cyrus L TamSeries Type : OtherOrganism : Homo sapiensThiol-linked alkylation for the metabolic sequencing of RNA (SLAM-seq) was used to measure genome-wide mRNA half-lives in patient-derived colorectal cancer (CRC) liver metastasis organoids (MSK107Li). Organoids expressing a doxycycline-inducible short hairpin RNA targeting ZFP36L2 (shZFP36L2) or a non-targeting control (shCtrl) were metabolically labeled with 500 μM 4-thiouridine (4sU) for 6 hours, followed by a uridine chase. Total RNA was harvested in triplicate at t=0, 2, 5, and 12 hours post-chase, along with matched unlabeled control samples for background T>C correction. RNA was subjected to iodoacetamide alkylation and libraries were prepared using the QuantSeq 3′ mRNA-seq V2 Library Prep Kit FWD (Lexogen). T>C conversion rates were used to quantify labeled RNA fractions and fit single-exponential decay models to estimate per-gene mRNA half-lives. ZFP36L2 knockdown significantly stabilized transcripts associated with stress-response gene programs, consistent with ZFP36L2 promoting post-transcriptional decay of AU-rich stress-associated mRNAs.
- 🔗 查看原文
9. GSE336416 ZFP36L2 协调肠道再生和结直肠癌转移中的应激适应性可塑性 (HyperTRIBE)
- ✍️ 作者:未知作者
- 🏷️ 关键词:cancer、regex:intestin(e|al)
- 📝 描述:Contributors : Karuna Ganesh ; Qingwen Jiang ; Jura Pintar ; Cyrus L TamSeries Type : OtherOrganism : Homo sapiensHyperTRIBE (Targets of RNA-binding proteins Identified By Editing) was used to identify genome-wide mRNA targets of ZFP36L2 in patient-derived colorectal cancer (CRC) and normal colon organoids. Full-length wild-type ZFP36L2 or the RNA-binding-incompetent frameshift mutant fsZFP36L2 (G144Afs*43) were fused to the hyperactive E488Q mutant catalytic domain of adenosine deaminase acting on RNA (ADAR) and expressed under a doxycycline-inducible Tet-on promoter, with a P2A-EGFP reporter to mark expressing cells. Constructs were stably integrated by lentiviral transduction into four organoid lines: two CRC liver metastasis lines (MSK107Li, OKG146Li), one matched primary tumour line (OKG146P), and one matched normal colon line (OKG146N). On day 5 post-seeding, organoids were treated with 2 μg/mL doxycycline for 2 days to induce transgene expression. GFP-positive live cells were isolated by flow cytometry, and total RNA was extracted using the RNeasy Mini Kit (Qiagen). mRNA libraries were prepared using the TruSeq Stranded mRNA Kit and sequenced on the Illumina NovaSeq 6000 (PE100). ZFP36L2-bound mRNAs were identified by comparing A-to-I editing events (read as A-to-G substitutions) enriched in ZFP36L2-ADAR versus fsZFP36L2-ADAR expressing organoids. Over 80% of ZFP36L2-specific edits occurred in mRNA 3′UTRs, predominantly at the conserved UAUUUA motif, consistent with known ZFP36 family RNA-binding properties.
- 🔗 查看原文
10. GSE336415 ZFP36L2 协调肠道再生和结直肠癌转移中的应激适应性可塑性 (ActDseq)
- ✍️ 作者:未知作者
- 🏷️ 关键词:cancer、regex:intestin(e|al)
- 📝 描述:Contributors : Karuna Ganesh ; Qingwen Jiang ; Jura Pintar ; Cyrus L TamSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensActinomycin D pulse-chase RNA sequencing (ActD-seq) was used to measure ZFP36L2-dependent mRNA decay rates in two patient-derived colorectal cancer (CRC) liver metastasis organoid lines (MSK107Li and OKG146Li). Organoids expressing a doxycycline-inducible short hairpin RNA targeting ZFP36L2 (shZFP36L2) or a non-targeting control (shCtrl) were cultured for 5 days with 2 μg/mL doxycycline, then treated with or without 5 μg/mL Actinomycin D (ActD) for 5 hours to block de novo transcription. Total RNA was extracted using the RNeasy Mini Kit (Qiagen), and strand-specific mRNA libraries were prepared using the TruSeq Stranded mRNA Kit and sequenced on the Illumina NovaSeq 6000 (PE100). Decay rates were quantified by comparing transcript abundance between ActD-treated and untreated conditions within each knockdown condition; ZFP36L2-dependent decay was calculated as the differential decay rate between shZFP36L2 and shCtrl. ZFP36L2 knockdown significantly stabilized stress-associated transcripts, consistent with ZFP36L2 promoting post-transcriptional decay of AU-rich stress-response mRNAs.
- 🔗 查看原文
💡 该来源还有 19 条内容,详见 文末
📊 关键词统计
| 关键词 | 出现次数 |
|---|---|
| cancer | 7 |
| regex:intestin(e | al) |
| immunity | 4 |
| dendritic cell | 3 |
| leukemia | 3 |
| scRNA | 2 |
| transcriptomics | 2 |
| immune | 2 |
| genome | 2 |
| methylation | 2 |
| RNA-seq | 2 |
| single-cell | 2 |
| ATAC-seq | 1 |
| aging | 1 |
| sequencing | 1 |
| spatial | 1 |
| spatial transcriptomics | 1 |
| RNAseq | 1 |
| pathway | 1 |
| inflammation | 1 |
📎 更多内容
🧬 数据前沿 其他内容 (19条)
- GSE330752:按前列腺重量分层的良性前列腺增生前列腺标本的单细胞RNA测序分析
- GSE330065 急性髓系白血病患者来源异种移植中DNA甲基化重塑的连续异种移植
- GSE329946 AML患者来源的异种移植瘤在连续移植过程中的单细胞RNA测序分析
- GSE327212 磷酸化调控开关控制皮层发育的时间 [scRNA]
- GSE338813 时间相位分辨转录组学揭示了转化鸡T细胞中马立克氏病病毒再激活的宿主决定因素
- GSE338810 疟原虫血液期诱导肝细胞产生训练免疫
- GSE338807 朗格汉斯细胞的双谱系协同作用,在皮肤损伤后恢复免疫屏障(bulkRNA-seq)
- GSE338796 胰岛素信号传导发挥拓扑开关的作用,将衰老和热应激反应联系起来
- GSE338793 小鼠黑色素瘤肿瘤中促进三级淋巴结构形成的癌症相关成纤维细胞群的特征分析
- GSE338745 细胞周期蛋白E过表达和电离辐射诱导野生型和RECQL4缺陷型U2OS细胞基因组不稳定
- GSE338713 解析长链 PFAS 破坏树突状细胞成熟的分子通路 [RNAseq_mDCs_96h]
- GSE338712 解析长链 PFAS 破坏树突状细胞成熟的分子通路 [RNAseq_mDCs_48h]
- GSE338576 解析长链 PFAS 破坏树突状细胞成熟的分子通路
- GSE334408 雷美替罗通过甲状腺激素受体α-脂肪酸酰胺水解酶1信号通路改善肝星状细胞纤维化
- GSE328260 转录组和功能分析揭示了光周期和隐花色素1在调节海胆(Strongylocentrotus intermedius)免疫中的作用
- GSE297915 SARS-CoV-2 患者皮肤先天免疫特征
- GSE330064 急性髓系白血病患者来源异种移植中连续异种移植的转化重塑
- GSE329505 急性髓系白血病连续异种移植过程中白血病干细胞状态和转录程序的演变
- GSE317014 RAG1缺陷小鼠真皮ILC2的内在重编程塑造皮肤炎症
📅 报告生成时间:2026-07-20 22:27
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