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Identification of aberrant plasma vesicles containing AAK1 and CCDC18-AS1 in adolescents with major depressive disorder and preliminary exploration of treatment efficacy. 青少年重度抑郁障碍中含有AAK1和CCDC18-AS1的异常血浆囊泡的鉴定及治疗效果的初步探讨
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-09 DOI: 10.1016/j.ygeno.2025.110993
Yifan Xu, Rong Zhang, Xinzhe Du, Yangxi Huang, Yao Gao, Yujiao Wen, Dan Qiao, Ning Sun, Zhifen Liu

Background: Major depressive disorder (MDD) during adolescence significantly jeopardizes both mental and physical health. However, the etiology underlying MDD in adolescents remains unclear.

Methods: A total of 74 adolescents with MDD and 40 health controls (HCs) who underwent comprehensive clinical and cognitive assessments were enrolled. Differential expression analysis was conducted on plasma extracellular vesicles (EVs) carrying long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) by microarray analysis. Two possible lncRNA-miR-mRNA networks were established and candidate regulatory axes were generated using the StarBase, miRDB, and TargetScan bioinformatics databases. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the candidate molecules and signaling axes in a clinical cohort.

Results: A total of 3752 dysregulated lncRNAs and 1789 dysfunctional mRNAs were identified. Two candidate regulatory axes (AC156455.1/miR-126-5p/AAK1 and CCDC18-AS1/miR-6835-5p/CCND2) with potential connections with MDD were selected. The candidate molecules exhibit differential expression patterns among adolescents with MDD and HCs, as well as before and after treatment with sertraline in adolescents with MDD. Furthermore, AAK1, CCDC18-AS1, and miR-6835-5p expressions exhibited significant differences between the response and non-response groups. Baseline expression of CCDC18-AS1, miR-6835-5p, and CCND2 could predict the therapeutic effect of sertraline, which may be associated with reducing suicidal ideation and improving cognitive function.

Conclusion: Our study may provide insights into the understanding of the underlying pathological mechanisms in adolescents with MDD.

背景:青春期重度抑郁障碍(MDD)严重危害身心健康。然而,青少年重度抑郁障碍的病因仍不清楚:方法:共招募了 74 名患有 MDD 的青少年和 40 名健康对照者(HCs),他们都接受了全面的临床和认知评估。通过微阵列分析对携带长非编码RNA(lncRNA)和信使RNA(mRNA)的血浆细胞外囊泡(EVs)进行了差异表达分析。利用StarBase、miRDB和TargetScan生物信息学数据库建立了两个可能的lncRNA-miR-mRNA网络,并生成了候选调控轴。利用定量实时聚合酶链反应(qRT-PCR)在临床队列中验证了候选分子和信号轴:结果:共鉴定出3752个调控失调的lncRNA和1789个功能失调的mRNA。结果:共鉴定出3752个表达失调的lncRNA和1789个功能失调的mRNA,并筛选出两个与MDD有潜在联系的候选调控轴(AC156455.1/miR-126-5p/AAK1和CCDC18-AS1/miR-6835-5p/CCND2)。候选分子在患有 MDD 的青少年和 HCs 之间以及患有 MDD 的青少年接受舍曲林治疗前后表现出不同的表达模式。此外,AAK1、CCDC18-AS1 和 miR-6835-5p 的表达在有反应组和无反应组之间存在显著差异。CCDC18-AS1、miR-6835-5p和CCND2的基线表达可预测舍曲林的治疗效果,这可能与减少自杀意念和改善认知功能有关:我们的研究可能有助于了解青少年 MDD 的潜在病理机制。
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引用次数: 0
Hepatic and intestinal insights into the molecular mechanisms of dietary Antarctic krill-induced body color differentiation in Plectropomus leopardus. 南极磷虾诱导的豹斑电鼠体色分化的肝脏和肠道分子机制。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-05 DOI: 10.1016/j.ygeno.2025.110989
Jiayi Wu, Mengya Wang, Xin Gao, Mingyi Wang, Chaofan Jin, Da Zheng, Jiangping Yan, Zhenmin Bao, Bo Wang, Jingjie Hu

Antarctic krill (Euphausia superba), which is rich in astaxanthin, has been widely utilized as a dietary supplement in fish aquaculture. Our study was to feed juvenile leopard coral grouper (Plectropomus leopardus) a diet containing 50 % Antarctic krill, revealing significant body color differentiation between a reddened group (BKR) and a non-reddened group (BKB), followed by comparative analysis with the control group (BCon) without krill supplementation. Histological analysis and carotenoid content in the liver and intestine were differentially regulated in color-differentiated individuals. Transcriptomic profiling revealed differentially expressed genes (DEGs) among color-differentiated individuals, with up-regulated DEGs in BKR being linked to carotenoid uptake, metabolism, and transport. Key DEGs (acss2l, insig1, fabp7, and bco1) were validated through qRT-PCR and FISH. Additionally, WGCNA identified potential gene regulatory networks in the liver and intestine that were responsive to the body coloration. This study elucidates the molecular mechanisms by which Antarctic krill influences carotenoid-based body coloration, offering new insights into the application of Antarctic krill in aquaculture.

南极磷虾(Euphausia superba)富含虾青素,已被广泛用作鱼类养殖的膳食补充剂。本研究以南极磷虾含量为50%的豹珊瑚石斑鱼幼鱼为研究对象,发现变红组(BKR)和未变红组(BKB)的体色存在显著差异,并与不添加磷虾的对照组(BCon)进行对比分析。组织学分析和肝脏和肠道类胡萝卜素含量在颜色分化个体中有差异调节。转录组学分析显示,在颜色分化个体中存在差异表达基因(DEGs), BKR中DEGs的上调与类胡萝卜素的摄取、代谢和运输有关。通过qRT-PCR和FISH验证关键基因(acss21、insig1、fabp7和bco1)。此外,WGCNA还发现了肝脏和肠道中对身体颜色有反应的潜在基因调控网络。本研究阐明了南极磷虾影响类胡萝卜素体色的分子机制,为南极磷虾在水产养殖中的应用提供了新的见解。
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引用次数: 0
Mechanistic insights into GLP-1 receptor agonist-induced weight loss through ceRNA network analysis. 通过ceRNA网络分析GLP-1受体激动剂诱导体重减轻的机制。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-04 DOI: 10.1016/j.ygeno.2025.110988
Wenxin Li, Xinyu Zhang, Jiamin Song, Ling Yang, Dong Wang, Guoyue Yuan, Li Zhao

Background: GLP-1 receptor agonists (GLP-1RA) have been extensively utilized in the management of body weight in individuals with obesity. Circular RNA (circRNA), a class of covalently closed RNA molecules, has garnered increasing attention for its potential role in the pathogenesis of obesity. However, the specific mechanisms through which circRNA contributes to GLP-1RA-induced weight loss remains elusive.

Methods: High-throughput sequencing analyzed epididymal adipose tissue from obese mice under high-fat, and GLP-1RA intervention (600 μg/kg/d). The functions of differentially expressed (DE) genes were enriched and analyzed. The circRNA-miRNA-mRNA interaction network was constructed in Cytoscape, and KEGG pathway gene enrichment was validated via western blotting.

Results: A total of 644 DEcircRNAs, 186 DEmiRNAs, and 3474 DEmRNAs were identified. Based on ceRNA score calculations, network diagrams were constructed. Gene Ontology (GO) analysis revealed that DERNAs were linked to lipid and fatty acid metabolism. DE genes within ceRNA pairs were enriched in lipid metabolism pathways, especially the PI3K-Akt and AMPK signaling pathways. GLP-1RA induced the phosphorylation of AKT and AMPK, which subsequently led to a reduction of SREBP-1, ACC, and FAS.

Conclusion: GLP-1RA might activate PI3K-Akt and AMPK signaling pathways to combat obesity through the ceRNA network of circRNAs.

背景:GLP-1受体激动剂(GLP-1RA)已广泛应用于肥胖个体的体重管理。环状RNA (circRNA)是一类共价闭合RNA分子,因其在肥胖发病机制中的潜在作用而受到越来越多的关注。然而,circRNA促进glp - 1ra诱导的体重减轻的具体机制仍然难以捉摸。方法:对高脂、GLP-1RA (600 μg/kg/d)干预下肥胖小鼠附睾脂肪组织进行高通量测序分析。对差异表达(DE)基因的功能进行了富集分析。在Cytoscape中构建circRNA-miRNA-mRNA相互作用网络,并通过western blotting验证KEGG通路基因富集。结果:共鉴定出644个decircrna, 186个demirna和3474个demmrna。基于ceRNA评分计算,构建网络图。基因本体(GO)分析显示,DERNAs与脂质和脂肪酸代谢有关。ceRNA对内DE基因富集于脂质代谢通路,尤其是PI3K-Akt和AMPK信号通路。GLP-1RA诱导AKT和AMPK的磷酸化,随后导致SREBP-1、ACC和FAS的减少。结论:GLP-1RA可能通过circRNAs的ceRNA网络激活PI3K-Akt和AMPK信号通路来对抗肥胖。
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引用次数: 0
Comparative effects of arecoline, caffeine, and nicotine on transcription level in the nucleus accumbens of mice. 槟榔碱、咖啡因和尼古丁对小鼠伏隔核转录水平的影响。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-04 DOI: 10.1016/j.ygeno.2025.110986
Shaofang Huang, Xinran Wang, Feifan Zhou

Though widely consumed, current research on the neural mechanisms of arecoline, caffeine, and nicotine remains limited, and the similarities and differences of these substances on the nervous system are still not clear. This study used RNA-seq to analyze the gene expression in the nucleus accumbens (NAc) of mice, and compared the behavioral changes through open field and conditioned place preference (CPP), exploring the effects of different psychoactive substances at transcriptional and behavioral levels. Gene Ontology enrichment analysis revealed that nicotine and caffeine significantly alter biological processes related to synaptic function, and KEGG pathway analysis showed that the differentially expressed genes in the nicotine-treated group were significantly more enriched in pathways related to substance dependence, with arecoline showing the least enrichment. Furthermore, only acute caffeine treatment significantly increased mouse activity, and only nicotine induced CPP. These results provided a scientific basis for evaluating arecoline, caffeine, and nicotine on the nervous system.

槟榔碱、咖啡因和尼古丁虽然被广泛使用,但目前对其神经机制的研究仍然有限,这些物质对神经系统的异同尚不清楚。本研究利用RNA-seq技术分析小鼠伏隔核(NAc)的基因表达,并通过开放场和条件位置偏好(CPP)比较其行为变化,探讨不同精神活性物质在转录和行为水平上的影响。基因本体富集分析显示,尼古丁和咖啡因显著改变了突触功能相关的生物学过程;KEGG通路分析显示,尼古丁处理组差异表达基因在物质依赖相关通路上的富集程度显著提高,槟榔碱的富集程度最低。此外,只有急性咖啡因处理显著增加小鼠活性,只有尼古丁诱导CPP。这些结果为评价槟榔碱、咖啡因和尼古丁对神经系统的影响提供了科学依据。
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引用次数: 0
Tissue-specific expression, functional analysis, and polymorphism of the KRT2 gene in sheep horn. 羊角KRT2基因的组织特异性表达、功能分析及多态性研究。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-04 DOI: 10.1016/j.ygeno.2025.110990
Hao Yang, Mingxing Chu, Naominggaowa, Xiaoxu Zhang, Mingzhu Shan, Xiaoning Lu, Zhangyuan Pan, Jianning He

Horn is a defensive weapon of sheep, consisting of a horny sheath and a bony core. The KRT2 gene is related to keratinization of the epidermis, so it is likely to be one of the contributor genes affecting horn type in sheep. In this study, we first analyzed the species-specific and tissue-specific expression of the KRT2 gene using transcriptome sequencing data. Then, by comparing the protein sequences of 20 species, we identified 28 specific amino acid sites in Artiodactyla animals, constructed a phylogenetic tree of the KRT2 gene, and predicted its three-dimensional protein structure. Finally, whole genome sequencing data was used and mined 4 functional SNP sites of KRT2 gene, and use KASP assay to verify the loci. In addition, we explored the relationship between the KRT2 gene and the evolution of Artiodactyla animals, and predicted the possible mechanism by which the KRT2 gene affects the horn type of sheep.

角是羊的防御武器,由角质鞘和骨核组成。KRT2基因与表皮角化有关,可能是影响绵羊角型的贡献基因之一。在本研究中,我们首先利用转录组测序数据分析了KRT2基因的物种特异性和组织特异性表达。然后,通过比较20种动物的蛋白质序列,鉴定出28个特定氨基酸位点,构建了KRT2基因的系统发育树,并预测了KRT2基因的三维蛋白质结构。最后利用全基因组测序数据挖掘KRT2基因的4个功能SNP位点,并利用KASP法对位点进行验证。此外,我们还探讨了KRT2基因与偶蹄目动物进化的关系,并预测了KRT2基因影响绵羊角型的可能机制。
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引用次数: 0
ARF3 as a novel biomarker and target in acute myeloid leukemia: Insights from pan-cancer analysis. ARF3作为急性髓系白血病的新生物标志物和靶点:来自泛癌症分析的见解。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-03 DOI: 10.1016/j.ygeno.2024.110984
Yang Wenli, Wang Wei, Pan Yubiao, Huang Hua, Tong Hongyan

Acute myeloid leukemia is a malignant hematologic disorder characterized by the excessive proliferation and accumulation of immature myeloid cells. This abnormality disrupts normal hematopoiesis, leading to symptoms such as anemia, increased susceptibility to infections and bleeding. ADP-ribosylation factors (ARFs) are critical in various cellular functions, including vesicular trafficking, membrane dynamics, cytoskeleton organization, signal transduction, endocytosis, exocytosis, and maintaining organelle integrity. Among ARF family members, ARF3 has garnered relatively less attention compared to other members like ARF1 and ARF6, leaving its role less understood. In this study, we found that the higher expression of ARF3 is correlated with poorer prognosis in AML patients. Silencing ARF3 in AML cells interrupted cell cycle progression and promote cell death as well as inhibit leukemogenesis in vivo. Mechanically, ARF3 knockdown suppressed AML progression by inhibiting PI3K/Akt signaling pathway. Our results indicate that ARF3 is linked to poor outcomes in AML patients and can serve as a potential therapeutic target for AML treatment.

急性髓系白血病是一种以未成熟髓系细胞过度增殖和积累为特征的恶性血液系统疾病。这种异常会破坏正常的造血功能,导致贫血、易感染和出血等症状。adp -核糖基化因子(ARFs)在各种细胞功能中起着至关重要的作用,包括囊泡运输、膜动力学、细胞骨架组织、信号转导、内吞作用、胞吐作用和维持细胞器完整性。在ARF家族成员中,与ARF1和ARF6等其他成员相比,ARF3获得的关注相对较少,因此对其作用的了解较少。在本研究中,我们发现ARF3的高表达与AML患者预后较差相关。在体内,在AML细胞中沉默ARF3可中断细胞周期进程,促进细胞死亡,并抑制白血病的发生。机械上,ARF3敲低通过抑制PI3K/Akt信号通路抑制AML进展。我们的研究结果表明,ARF3与AML患者的不良预后有关,可以作为AML治疗的潜在治疗靶点。
{"title":"ARF3 as a novel biomarker and target in acute myeloid leukemia: Insights from pan-cancer analysis.","authors":"Yang Wenli, Wang Wei, Pan Yubiao, Huang Hua, Tong Hongyan","doi":"10.1016/j.ygeno.2024.110984","DOIUrl":"10.1016/j.ygeno.2024.110984","url":null,"abstract":"<p><p>Acute myeloid leukemia is a malignant hematologic disorder characterized by the excessive proliferation and accumulation of immature myeloid cells. This abnormality disrupts normal hematopoiesis, leading to symptoms such as anemia, increased susceptibility to infections and bleeding. ADP-ribosylation factors (ARFs) are critical in various cellular functions, including vesicular trafficking, membrane dynamics, cytoskeleton organization, signal transduction, endocytosis, exocytosis, and maintaining organelle integrity. Among ARF family members, ARF3 has garnered relatively less attention compared to other members like ARF1 and ARF6, leaving its role less understood. In this study, we found that the higher expression of ARF3 is correlated with poorer prognosis in AML patients. Silencing ARF3 in AML cells interrupted cell cycle progression and promote cell death as well as inhibit leukemogenesis in vivo. Mechanically, ARF3 knockdown suppressed AML progression by inhibiting PI3K/Akt signaling pathway. Our results indicate that ARF3 is linked to poor outcomes in AML patients and can serve as a potential therapeutic target for AML treatment.</p>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":" ","pages":"110984"},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ribosome profiling reveals dynamic translational landscape following X-ray irradiation. 核糖体分析揭示x射线照射后HEK293T细胞的动态翻译景观。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-02 DOI: 10.1016/j.ygeno.2025.110987
Jingyu Hou, Lei Yu, Canlan Wu, Saisai Wei, Xiangwei Gao

X-ray irradiation induces widespread changes in gene expression. Positioned at the bottom of the central dogma, translational regulation responds swiftly to environmental stimuli, fine-tuning protein levels. However, the global view of mRNA translation following X-ray exposure remains unclear. In this study, we systematically investigated X-ray-induced translational alternation using ribosome profiling. Our study revealed a temporary translation inhibition in HEK293T cells following X-ray treatment. A subset of mRNAs experienced translational upregulation by bypassing upstream open reading frames (uORFs). The upregulated genes were enriched in the MAPK signaling pathway, such as MAPKBP1. Suppression of MAPKBP1 inhibited X-ray-induced cell apoptosis. Furthermore, we identified the induction of novel peptides encoded by small open reading frames (smORFs) within long non-coding RNAs (lncRNAs) upon X-ray treatment. Overall, our findings provide a comprehensive overview of the translational landscape within eukaryotic cells following X-ray treatment, offering new insights into DNA damage response.

x射线照射引起基因表达的广泛变化。位于中心法则的底部,翻译调控对环境刺激反应迅速,微调蛋白质水平。然而,x射线照射后mRNA翻译的整体观点仍不清楚。在这项研究中,我们使用核糖体分析系统地研究了x射线诱导的翻译交替。我们的研究揭示了x射线治疗后HEK293T细胞的暂时翻译抑制。mrna的一个子集通过绕过上游开放阅读框(uorf)经历了翻译上调。上调基因在MAPK信号通路中富集,如MAPKBP1。抑制MAPKBP1抑制x射线诱导的细胞凋亡。此外,我们发现x射线处理诱导长链非编码rna (lncRNAs)中由小开放阅读框(smorf)编码的新肽。总的来说,我们的研究结果提供了真核细胞在x射线治疗后的翻译景观的全面概述,为DNA损伤反应提供了新的见解。
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引用次数: 0
Key role of CYP17A1 in Leydig cell function and testicular development in Qianbei Ma goats CYP17A1 在黔北麻山羊的精原细胞功能和睾丸发育中的关键作用
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.ygeno.2024.110937
Tang Wen , Zhang Yuan , Wang Zhong , Guo Wei , Chen Jiajing , Ji Quan , Wang Yanfei , Li Ruiyang , Xu Houqiang , Chen Xiang
Reproductive traits are vital economic parameters in goat production, and boosting the reproductive capacity of breeding rams is crucial for enhancing the profitability of goat farming. Currently, research on the reproductive performance of Qianbei Ma goats mainly centers on investigating mechanisms associated with prolificacy and estrous ovulation in ewes, with limited emphasis on ram reproductive aspects. This study used scanning electron microscopy and enzyme-linked immunosorbent assay (ELISA) to profile the morphology of testis and the dynamic changes of Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), and Testosterone (T) in serum at different developmental stages of Qianbei Ma goats. Meanwhile, transcriptome sequencing technology was used to investigate the mRNA expression patterns in testicular tissues at different developmental stages: newborn (0 M), puberty (6 M), sexual maturity (12 M), and physical maturity (18 M). The results showed that the diameter, circumference, and area of the testicular seminiferous tubules gradually increased with age. The levels of T and LH in serum significantly increased from 0 to 6 months after birth (p < 0.05), followed by a stabilization of T levels and a significant decrease in LH levels (p < 0.05). Meanwhile, FSH shows a decreasing trend between 0 and 18 months after birth. A total of 26,437 differentially expressed genes were identified in 6 comparison groups, which involve various biological processes such as immunity, growth, metabolism, development, and reproduction, and are significantly enriched in signaling pathways related to testicular development and spermatogenesis. WGCNA analysis identified 6 regions significantly associated with testicular development and spermatogenesis, and selected 320 genes for constructing a PPI network. Ten candidate genes related to testicular development and spermatogenesis were identified, including TP53, PLK4, RPS9, PFN4, ACTB, CYP17A1, GPX4, CLDN1, AMH and DHH. Of these, the CYP17A1 gene promotes interstitial cell proliferation, and promotes T synthesis. This study provides a theoretical basis and data support for promoting efficient breeding of goats and early breeding of excellent male goats.
繁殖性状是山羊生产中至关重要的经济参数,提高种公羊的繁殖能力对提高山羊养殖业的收益至关重要。目前,对黔北麻山羊繁殖性能的研究主要集中在母羊多产和发情排卵相关机制的研究上,对公羊繁殖方面的研究较少。本研究利用扫描电镜和酶联免疫吸附试验(ELISA)分析了黔北麻羊不同发育阶段睾丸的形态以及血清中促黄体素(LH)、促卵泡激素(FSH)和睾酮(T)的动态变化。同时,利用转录组测序技术研究了黔北麻羊不同发育阶段(初生(0 M)、青春期(6 M)、性成熟(12 M)和体成熟(18 M))睾丸组织中 mRNA 的表达模式。结果显示,随着年龄的增长,睾丸曲细精管的直径、周长和面积逐渐增大。从出生后 0 个月到 6 个月,血清中的 T 和 LH 水平明显升高(p
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引用次数: 0
High-resolution dissection of human cell type-specific enhancers in cis and trans activities 人类细胞类型特异性增强子在顺式和反式活动中的高分辨率解剖。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.ygeno.2025.110985
Meng Wang, Xiaoxu Yang, Qixi Wu
The spatiotemporal-specific gene expression is regulated by cell type-specific regulatory elements. Here we selected the H3K4me1-associated DNA sequences as candidate enhancers in two different human cell lines and performed ChIP-STARR-seq to quantify the cell-type-specific enhancer activities with high-resolution. We investigated how the activity landscape of enhancers would change when transferred from native cells (cis activity) to another cell lines (trans activity). We obtained enhancers cis activity maps and trans activity maps in two different cell lines. The cis and trans activity maps enabled us to identify cell type-specific active enhancers, with enrichment of motifs of differentially expressed TFs. Comparisons between the cis and trans activity maps revealed general consistent regulatory property with different levels of activity in two cell lines, suggesting sequence intrinsic regulatory properties remain similar in different types of cells. This study provides a new perspective on sequence intrinsic enhancer activities in different types of cells.
时空特异性基因表达受细胞类型特异性调控元件的调控。在这里,我们选择了h3k4me1相关的DNA序列作为两种不同人类细胞系的候选增强子,并使用ChIP-STARR-seq以高分辨率量化细胞类型特异性增强子的活性。我们研究了当增强子库从原生细胞(顺式活性)转移到其他细胞系(反式活性)时,增强子库的活性景观将如何变化。我们在两种不同的细胞系中获得了顺式活性图和反式活性图。顺式和反式活性图谱使我们能够识别细胞类型特异性活性增强子,并富集差异表达tf的基序。顺式和反式活性图谱的比较显示,在两种细胞系中,不同活性水平的序列内在调控特性大致一致,这表明序列内在调控特性在不同类型的细胞中保持相似。本研究为研究序列内在增强子在不同类型细胞中的活性提供了新的视角。
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引用次数: 0
Expansion of peripheral cytotoxic CD4+ T cells in Alzheimer's disease: New insights from multi-omics evidence 阿尔茨海默病外周血细胞毒性CD4+ T细胞的扩增:来自多组学证据的新见解
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.ygeno.2024.110976
Jiongxue Chen , Jiatian Xie , Fuyin Deng , Jinhua Cai , Sitai Chen , Xingrong Song , Shangzhou Xia , Qingyu Shen , Xinying Guo , Yamei Tang
The significance of the adaptive immune response in Alzheimer's disease (AD) is increasingly recognized. We analyzed scRNA-Seq data from AD patients, revealing a notable rise in CD4 cytotoxic T cells (CD4-CTLs) in peripheral blood mononuclear cells (PBMCs), validated in vivo and in vitro. This rise correlates with cognitive decline in AD patients. We also identified transcription factors TBX21 and MYBL1 as key drivers of CD4-CTL expansion. Further analyses indicate these cells are terminally differentiated, showing clonal expansion, metabolic changes, and unique communication patterns. Mendelian randomization identified risk genes SRGN and ITGB1, suggesting their genetic regulation in CD4-CTLs may contribute to AD. To summarize, our findings characterize the expansion of CD4-CTLs in the PBMCs of AD patients, providing valuable understanding into the possible mechanisms involved in the expansion of CD4-CTLs in AD.
适应性免疫反应在阿尔茨海默病(AD)中的重要性越来越被认识到。我们分析了来自AD患者的scRNA-Seq数据,揭示了外周血单核细胞(PBMCs)中CD4细胞毒性T细胞(CD4- ctl)的显著升高,这在体内和体外都得到了验证。这种上升与阿尔茨海默病患者的认知能力下降有关。我们还发现转录因子TBX21和MYBL1是CD4-CTL扩增的关键驱动因素。进一步的分析表明,这些细胞是终末分化的,表现出克隆扩增、代谢变化和独特的通讯模式。孟德尔随机化鉴定出风险基因SRGN和ITGB1,提示它们在cd4 - ctl中的遗传调控可能与AD有关。总之,我们的研究结果表征了AD患者PBMCs中cd4 - ctl的扩增,为AD中cd4 - ctl扩增的可能机制提供了有价值的理解。
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引用次数: 0
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Genomics
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