single-cell analysis

单细胞分析
  • 文章类型: Journal Article
    卵巢癌是卵巢的恶性肿瘤。具有早期诊断困难的特点,晚期疗效差,复发率高。它是严重威胁女性健康的最大疾病。单细胞测序技术是指在单细胞水平对其携带的遗传信息进行测序,以获得基因序列,抄本,抄本细胞类型的蛋白质和表观遗传表达谱信息进行整合分析。在研究肿瘤的发生和演变过程中具有独特的优势,为卵巢癌的研究提供新的方法。本文就单细胞测序技术及其在卵巢癌中的应用作一综述。
    Ovarian cancer is a malignant tumor of ovary. It has the characteristics of difficult early diagnosis, poor late curative effect and high recurrence rate. It is the biggest disease that seriously threatens women\'s health. Single cell sequencing technology refers to sequencing the genetic information carried by it at the single cell level to obtain the gene sequence, transcript, protein and epigenetic expression profile information of a certain cell type and conduct integrated analysis. It has unique advantages in the study of tumor occurrence and evolution, and can provide new methods for the study of ovarian cancer. This paper reviews the single cell sequencing technology and its application in ovarian cancer.
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  • 文章类型: Journal Article
    阿尔茨海默病(Alzheimer’sdisease,AD)是一种多方面的神经退行性疾病,其特征是认知功能逐渐恶化和神经元丢失。虽然传统的批量RNA测序技术已经揭示了AD病理学,它们经常掩盖脑组织内的细胞多样性。单细胞RNA测序(scRNA-seq)的出现改变了我们分析AD细胞组成的能力。允许检测独特的细胞群,稀有细胞类型,和单个细胞水平的基因表达改变。这篇综述探讨了scRNA-seq在AD研究中的应用,专注于它对理解细胞多样性的贡献,疾病进展,和潜在的治疗目标。我们讨论关键的技术创新,数据分析技术,以及与scRNA-seq研究AD相关的挑战。此外,我们重点介绍了最近利用scRNA-seq来鉴定新型生物标志物的研究,揭示疾病相关途径,阐明非神经元细胞的作用,比如小胶质细胞和星形胶质细胞,在AD发病机制中。通过全面概述scRNA-seq的进展,以揭示AD中的细胞异质性,这篇综述强调了scRNA-seq对我们对疾病机制的理解和靶向治疗的产生的转化作用.
    Alzheimer\'s disease (AD) is a multifaceted neurodegenerative condition marked by gradual cognitive deterioration and the loss of neurons. While conventional bulk RNA sequencing techniques have shed light on AD pathology, they frequently obscure the cellular diversity within brain tissues. The advent of single-cell RNA sequencing (scRNA-seq) has transformed our capability to analyze the cellular composition of AD, allowing for the detection of unique cell populations, rare cell types, and gene expression alterations at an individual cell level. This review examines the use of scRNA-seq in AD research, focusing on its contributions to understanding cellular diversity, disease progression, and potential therapeutic targets. We discuss key technological innovations, data analysis techniques, and challenges associated with scRNA-seq in studying AD. Furthermore, we highlight recent studies that have utilized scRNA-seq to identify novel biomarkers, uncover disease-associated pathways, and elucidate the role of non-neuronal cells, such as microglia and astrocytes, in AD pathogenesis. By providing a comprehensive overview of advancements in scRNA-seq for unraveling cellular heterogeneity in AD, this review highlights the transformative impact of scRNA-seq on our comprehension of disease mechanisms and the creation of targeted treatments.
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  • 文章类型: Journal Article
    最近构建细胞表型参考图的努力扩大了单细胞组学数据的数量和多样性,为研究细胞特性提供了前所未有的资源。尽管有丰富的数据集和它们的持续增长,当前的单细胞模型无法充分利用它们包含的信息。变形金刚已经成为其他领域基础模型的首选架构,因为它们能够概括为异构,大规模数据集。因此,问题是变压器是否可以在单细胞建模领域引发类似的转变。在这里,我们首先描述变压器架构及其单细胞适应,然后全面回顾变压器在单细胞分析中的现有应用,并批判性地讨论它们在单细胞生物学中的未来潜力。通过研究局限性和技术挑战,我们的目标是在机器学习和单细胞生物学的交叉点为未来的研究方向提供一个结构化的展望。
    Recent efforts to construct reference maps of cellular phenotypes have expanded the volume and diversity of single-cell omics data, providing an unprecedented resource for studying cell properties. Despite the availability of rich datasets and their continued growth, current single-cell models are unable to fully capitalize on the information they contain. Transformers have become the architecture of choice for foundation models in other domains owing to their ability to generalize to heterogeneous, large-scale datasets. Thus, the question arises of whether transformers could set off a similar shift in the field of single-cell modeling. Here we first describe the transformer architecture and its single-cell adaptations and then present a comprehensive review of the existing applications of transformers in single-cell analysis and critically discuss their future potential for single-cell biology. By studying limitations and technical challenges, we aim to provide a structured outlook for future research directions at the intersection of machine learning and single-cell biology.
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  • 文章类型: Journal Article
    糖尿病肾病(DKD)是终末期肾病(ESRD)的主要原因,其发病机制尚未明确。目前的研究表明,DKD涉及多种细胞类型和肾外因素,阐明发病机制和确定新的治疗靶点尤为重要。单细胞RNA测序(scRNA-seq)技术是在单细胞水平上对单个细胞的转录组进行高通量测序,这是一种通过比较遗传信息来探索疾病发展的有效技术,反映了细胞之间遗传信息的差异,识别不同的细胞亚群。越来越多的证据支持scRNA-seq在揭示糖尿病发病机制和加强我们对DKD分子机制的理解中的作用。这次我们回顾了scRNA-seq数据。然后,我们分析和讨论了scRNA-seq技术在DKD研究中的应用,包括细胞类型的注释,新细胞类型(或亚型)的鉴定,细胞间通讯的识别,细胞分化轨迹分析,基因表达检测,和分析基因调控网络,最后,我们探讨了scRNA-seq技术在DKD研究中的未来前景。
    Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), and its pathogenesis has not been clarified. Current research suggests that DKD involves multiple cell types and extra-renal factors, and it is particularly important to clarify the pathogenesis and identify new therapeutic targets. Single-cell RNA sequencing (scRNA-seq) technology is high-throughput sequencing of the transcriptomes of individual cells at the single-cell level, which is an effective technology for exploring the development of diseases by comparing genetic information, reflecting the differences in genetic information between cells, and identifying different cell subpopulations. Accumulating evidence supports the role of scRNA-seq in revealing the pathogenesis of diabetes and strengthening our understanding of the molecular mechanisms of DKD. We reviewed the scRNA-seq data this time. Then, we analyzed and discussed the applications of scRNA-seq technology in DKD research, including annotation of cell types, identification of novel cell types (or subtypes), identification of intercellular communication, analysis of cell differentiation trajectories, gene expression detection, and analysis of gene regulatory networks, and lastly, we explored the future perspectives of scRNA-seq technology in DKD research.
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  • 文章类型: Journal Article
    成纤维细胞是人体内最丰富的细胞类型之一,在许多生理过程中发挥关键作用,包括真皮的结构维护,细胞外基质成分的产生,和炎症反应的调解。尽管它们很重要,成纤维细胞仍然是特征最少的细胞群体之一。单细胞分析技术的出现,特别是单细胞RNA测序(scRNA-seq)和荧光激活细胞分选(FACS),已经能够对成纤维细胞生物学进行详细的研究。在这项研究中,我们对适用于细胞分选和后续功能研究的成纤维细胞表面标志物进行了广泛的分析.我们回顾了超过三千篇描述成纤维细胞群体及其标记的研究文章,根据其表面标记表征和比较亚型,以及它们的细胞内和细胞外蛋白。我们的详细分析确定了各种不同的成纤维细胞亚群,每个都有独特的标记,取决于它们的位置的特征,和生理或病理生理环境。这些发现强调了成纤维细胞作为细胞群体的多样性,并可能导致新型诊断和治疗工具的开发。
    Fibroblasts are among the most abundant cell types in the human body, playing crucial roles in numerous physiological processes, including the structural maintenance of the dermis, production of extracellular matrix components, and mediation of inflammatory responses. Despite their importance, fibroblasts remain one of the least characterized cell populations. The advent of single-cell analysis techniques, particularly single-cell RNA sequencing (scRNA-seq) and fluorescence-activated cell sorting (FACS), has enabled detailed investigations into fibroblast biology. In this study, we present an extensive analysis of fibroblast surface markers suitable for cell sorting and subsequent functional studies. We reviewed over three thousand research articles describing fibroblast populations and their markers, characterizing and comparing subtypes based on their surface markers, as well as their intra- and extracellular proteins. Our detailed analysis identified a variety of distinct fibroblast subpopulations, each with unique markers, characteristics dependent on their location, and the physiological or pathophysiological environment. These findings underscore the diversity of fibroblasts as a cellular population and could lead to the development of novel diagnostic and therapeutic tools.
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  • 文章类型: Journal Article
    体外成熟(IVM)是非阻塞性无精子症患者或青春期前男孩获得受精能力精子的有希望的生育能力恢复策略。然而,人未成熟睾丸组织仍未实现体外精子发生。了解不同发育时期的各种人类睾丸转录谱有助于我们更好地了解睾丸发育。本范围审查旨在描述从胎儿期到成年的睾丸发育和成熟,并找到优化IVM的信息。鉴定了与天然和体外培养的人睾丸细胞和单细胞RNA测序(scRNA-seq)相关的研究论文,并进行了严格的审查。特别关注基因本体论术语,以利于解释相关基因的生物学功能。描述了胚芽和体细胞谱系的不同连续成熟状态。ScRNA-seq通常在11岁左右显示出重大变化,最终达到成年状态。描述了不同的精原干细胞(SSC)亚细胞,scRNA-seq分析有利于范式转变,由于在不同的SSC状态中无法明确识别Adark和Apale精原细胞种群。体细胞谱系的数据有限,特别是对于支持细胞,由于与细胞大小有关的技术问题。在细胞培养过程中,scRNA-seq数据显示,在存在AKT信号传导途径抑制剂的情况下,未分化的SSC是有利的。氧化磷酸化途径的参与取决于细胞的成熟状态。睾丸发育和成熟过程中常见的细胞信号传导途径突出了在IVM的特定成熟期可能必不可少的因素。
    In vitro maturation (IVM) is a promising fertility restoration strategy for patients with nonobstructive azoospermia or for prepubertal boys to obtain fertilizing-competent spermatozoa. However, in vitro spermatogenesis is still not achieved with human immature testicular tissue. Knowledge of various human testicular transcriptional profiles from different developmental periods helps us to better understand the testis development. This scoping review aims to describe the testis development and maturation from the fetal period towards adulthood and to find information to optimize IVM. Research papers related to native and in vitro cultured human testicular cells and single-cell RNA-sequencing (scRNA-seq) were identified and critically reviewed. Special focus was given to gene ontology terms to facilitate the interpretation of the biological function of related genes. The different consecutive maturation states of both the germ and somatic cell lineages were described. ScRNA-seq regularly showed major modifications around 11 years of age to eventually reach the adult state. Different spermatogonial stem cell (SSC) substates were described and scRNA-seq analyses are in favor of a paradigm shift, as the Adark and Apale spermatogonia populations could not distinctly be identified among the different SSC states. Data on the somatic cell lineage are limited, especially for Sertoli cells due technical issues related to cell size. During cell culture, scRNA-seq data showed that undifferentiated SSCs were favored in the presence of an AKT-signaling pathway inhibitor. The involvement of the oxidative phosphorylation pathway depended on the maturational state of the cells. Commonly identified cell signaling pathways during the testis development and maturation highlight factors that can be essential during specific maturation stages in IVM.
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  • 文章类型: Journal Article
    肠道是人体最大的屏障器官。肠屏障在维持肠道环境平衡和保护肠道免受有害细菌入侵方面起着至关重要的作用。单细胞RNA测序技术允许在两个维度上检测肠道中的不同细胞类型,并探索尚未完全表征的细胞类型。肠粘膜结构非常复杂,它的正常功能与近端远端肠和腔粘膜轴中的多个结构有关。空间定位是探索复杂结构之间相互作用的核心。空间转录组学(ST)是一种可以进行全面组织分析和从单个细胞中获取空间分离的遗传信息的方法,同时保留它们的空间位置和相互作用。该方法还防止组织解聚期间脆性细胞的损失。ST技术的出现使我们能够在空间上解剖酶促过程和多个细胞之间的相互作用,基因,肠道中的蛋白质和信号。这包括肠道中氧气和营养物质的交换,不同梯度的微生物种群和细胞外基质蛋白的作用。这种区域精确的组织研究方法正在获得更多的接受,并越来越多地用于研究与胃肠道相关的疾病机制。因此,本文就ST在胃肠道疾病中的应用作一综述。
    The intestines are the largest barrier organ in the human body. The intestinal barrier plays a crucial role in maintaining the balance of the intestinal environment and protecting the intestines from harmful bacterial invasion. Single‑cell RNA sequencing technology allows the detection of the different cell types in the intestine in two dimensions and the exploration of cell types that have not been fully characterized. The intestinal mucosa is highly complex in structure, and its proper functioning is linked to multiple structures in the proximal‑distal intestinal and luminal‑mucosal axes. Spatial localization is at the core of the efforts to explore the interactions between the complex structures. Spatial transcriptomics (ST) is a method that allows for comprehensive tissue analysis and the acquisition of spatially separated genetic information from individual cells, while preserving their spatial location and interactions. This approach also prevents the loss of fragile cells during tissue disaggregation. The emergence of ST technology allows us to spatially dissect enzymatic processes and interactions between multiple cells, genes, proteins and signals in the intestine. This includes the exchange of oxygen and nutrients in the intestine, different gradients of microbial populations and the role of extracellular matrix proteins. This regionally precise approach to tissue studies is gaining more acceptance and is increasingly applied in the investigation of disease mechanisms related to the gastrointestinal tract. Therefore, this review summarized the application of ST in gastrointestinal diseases.
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  • 文章类型: Journal Article
    背景:肝癌(LC)是一种普遍的恶性肿瘤,是全球癌症相关死亡率的主要原因。进行了广泛的研究,以提高患者的治疗效果并制定有效的预防策略,从分子机制到临床干预。单细胞测序,作为一种新颖的生物分析技术,显著促进了对肝癌整体认知和动态变化的理解。然而,在这一具体研究领域缺乏文献计量学分析。因此,本研究的目的是通过文献计量学的方法,对肝癌研究中单细胞测序领域的知识结构和研究热点进行全面概述。
    方法:在科学核心收藏(WoSCC)数据库的网络上搜索了截至2023年12月31日与单细胞测序技术在肝癌研究中的应用有关的出版物。听者,CiteSpace,和R包“bibliometrix”用于进行此文献计量分析。
    结果:共有来自34个国家的331种出版物,主要由中国和美国领导,包括在这项研究中。研究重点是单细胞测序技术在肝癌中的应用,相关出版物的数量逐年增加。参与这一领域的主要研究机构是复旦大学,中山大学,和中国科学院。免疫学和自然通讯前沿是该领域最受欢迎的期刊,而Cell是最常被共同引用的期刊。这些出版物由2799人撰写,范佳和周健发表的论文最多,LlovetJm是最常被共同引用的作者。利用单细胞测序探索肝癌的免疫微环境,以及它在免疫疗法和化疗中的意义,仍然是这个领域的焦点。新兴的研究热点以“基因表达”等关键词为特征,\'预后\',\'肿瘤异质性\',\'免疫调节\',和“肿瘤免疫微环境”。
    结论:这是第一个文献计量学研究,全面总结了单细胞测序在肝癌中应用的研究趋势和进展。这项研究确定了最近的研究前沿和热点方向,为研究人员探索肝癌的景观提供了有价值的参考,了解免疫微环境的组成,利用单细胞测序技术指导和提高肝癌患者的预后。
    BACKGROUND: Liver cancer (LC) is a prevalent malignancy and a leading cause of cancer-related mortality worldwide. Extensive research has been conducted to enhance patient outcomes and develop effective prevention strategies, ranging from molecular mechanisms to clinical interventions. Single-cell sequencing, as a novel bioanalysis technology, has significantly contributed to the understanding of the global cognition and dynamic changes in liver cancer. However, there is a lack of bibliometric analysis in this specific research area. Therefore, the objective of this study is to provide a comprehensive overview of the knowledge structure and research hotspots in the field of single-cell sequencing in liver cancer research through the use of bibliometrics.
    METHODS: Publications related to the application of single-cell sequencing technology to liver cancer research as of December 31, 2023, were searched on the web of science core collection (WoSCC) database. VOSviewers, CiteSpace, and R package \"bibliometrix\" were used to conduct this bibliometric analysis.
    RESULTS: A total of 331 publications from 34 countries, primarily led by China and the United States, were included in this study. The research focuses on the application of single cell sequencing technology to liver cancer, and the number of related publications has been increasing year by year. The main research institutions involved in this field are Fudan University, Sun Yat-Sen University, and the Chinese Academy of Sciences. Frontiers in Immunology and Nature Communications is the most popular journal in this field, while Cell is the most frequently co-cited journal. These publications are authored by 2799 individuals, with Fan Jia and Zhou Jian having the most published papers, and Llovet Jm being the most frequently co-cited author. The use of single cell sequencing to explore the immune microenvironment of liver cancer, as well as its implications in immunotherapy and chemotherapy, remains the central focus of this field. The emerging research hotspots are characterized by keywords such as \'Gene-Expression\', \'Prognosis\', \'Tumor Heterogeneity\', \'Immunoregulation\', and \'Tumor Immune Microenvironment\'.
    CONCLUSIONS: This is the first bibliometric study that comprehensively summarizes the research trends and developments on the application of single cell sequencing in liver cancer. The study identifies recent research frontiers and hot directions, providing a valuable reference for researchers exploring the landscape of liver cancer, understanding the composition of the immune microenvironment, and utilizing single-cell sequencing technology to guide and enhance the prognosis of liver cancer patients.
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  • 文章类型: Systematic Review
    近年来,研究方法的快速发展使单细胞分析成为可能。系统性硬化症(SSc),一种以免疫异常为特征的疾病,纤维化,血管病变,也是各种分析的主题。总结迄今为止积累的SSc单细胞分析结果,加深对SSc的理解。2023年6月23日,使用了四个数据库进行数据库搜索。建议评估的评估等级,根据PRISMA指南制定和评估证据的确定性。该分析于2023年7月完成。纳入了358名SSc患者的17项研究。三项研究使用PBMC,六种用过的皮肤,9例患有SSc间质性肺病(ILD)的二手肺,和一个使用肺SSc肺动脉高压(PAH)。研究的细胞包括免疫细胞,如T细胞,自然杀伤细胞,单核细胞,巨噬细胞,和树突状细胞,以及内皮细胞,成纤维细胞,角质形成细胞,肺泡I型细胞,基底上皮细胞,平滑肌细胞,间皮细胞,等。本系统综述揭示了单细胞分析的结果,表明PBMC,皮肤,SSc-ILD,和SSc-PAH显示与免疫异常相关的细胞的激活和功能障碍,纤维化,血管病变,分别。
    In recent years, rapid advances in research methods have made single cell analysis possible. Systemic sclerosis (SSc), a disease characterized by the triad of immune abnormalities, fibrosis, and vasculopathy, has also been the subject of various analyses. To summarize the results of single cell analysis in SSc accumulated to date and to deepen our understanding of SSc. Four databases were used to perform a database search on 23rd June 2023. Assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed according to PRISMA guidelines. The analysis was completed on July 2023. 17 studies with 358 SSc patients were included. Three studies used PBMCs, six used skin, nine used lung with SSc-interstitial lung diseases (ILDs), and one used lung with SSc-pulmonary arterial hypertension (PAH). The cells studied included immune cells such as T cells, natural killer cells, monocytes, macrophages, and dendritic cells, as well as endothelial cells, fibroblasts, keratinocytes, alveolar type I cells, basal epithelial cells, smooth muscle cells, mesothelial cells, etc. This systematic review revealed the results of single cell analysis, suggesting that PBMCs, skin, SSc-ILD, and SSc-PAH show activation and dysfunction of cells associated with immune-abnormalities, fibrosis, and vasculopathy, respectively.
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  • 文章类型: Journal Article
    细胞的精确机械测量具有改善诊断的潜力,治疗学和对疾病机制的深入理解,其中高分辨率的机械信息可以通过变形单个细胞来测量。在这里,我们评估了最近开发的用于测量细胞尺度刚度特性的技术;虽然已经开发了许多这样的技术,检查单细胞刚度的大部分工作都受到标准化和可比性方面的困难的影响,导致报告的机械模量有很大的变化。我们强调了驱动这种可变性的潜在机械理论的作用,并注意开发新的机械分型设备和理论模型的机会,以促进方便和准确的机械表征。此外,许多高通量方法受到包括细胞大小在内的因素的混淆,表面摩擦,自然种群异质性和弹性和粘性贡献对细胞变形性的卷积。尽管如此,我们还是将基于可变形性细胞计数的关键方法确定为进一步发展的有希望的方向,可以实现高通量和精确的单细胞分辨率。
    Accurate mechanical measurements of cells has the potential to improve diagnostics, therapeutics and advance understanding of disease mechanisms, where high-resolution mechanical information can be measured by deforming individual cells. Here we evaluate recently developed techniques for measuring cell-scale stiffness properties; while many such techniques have been developed, much of the work examining single-cell stiffness is impacted by difficulties in standardization and comparability, giving rise to large variations in reported mechanical moduli. We highlight the role of underlying mechanical theories driving this variability, and note opportunities to develop novel mechanotyping devices and theoretical models that facilitate convenient and accurate mechanical characterisation. Moreover, many high-throughput approaches are confounded by factors including cell size, surface friction, natural population heterogeneity and convolution of elastic and viscous contributions to cell deformability. We nevertheless identify key approaches based on deformability cytometry as a promising direction for further development, where both high-throughput and accurate single-cell resolutions can be realized.
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