单细胞文章快讯202108期

本期我们通过PubMed数据库检索，整理了从2021年8月1日到8月31单细胞技术文章共764篇。其中IF (影响因子)大于9分的文章有216篇（文章后面使用表格列出），现选择其中20篇代表性文章进行导读，详情如下：

1英文题目：Molecular phenotyping reveals the identity of Barrett's esophagus and its malignant transition中文题目：分子表型揭示巴雷特食管的特征及其恶性转变发表时间：2021-08-13发表杂志：Science影响因子：47.720DOI：10.1126/science.abd1449

摘要：人类化生状态的起源及其致癌倾向尚不清楚。Barrett食管是一种常见的化生性疾病，会增加食管腺癌的发病风险，其细胞起源不明。为了解决这个问题，我们从健康和患病供体中采集了跨越胃食管连接处的组织，包括分离食管粘膜下腺。单细胞转录组分析、甲基化的计算机谱系追踪、开放染色质和体细胞突变分析以及类器官模型的功能研究表明，Barrett食管通过 c-MYC 和 HNF4A 驱动的转录程序起源于贲门。此外，我们的数据表明，食管腺癌可能源自未分化的Barrett食管细胞类型，即使在缺乏病理学上可识别的化生全体的情况下，这也揭示了早期的检测策略。

2英文题目：Spatial transcriptomics of planktonic and sessile bacterial populations at single-cell resolution中文题目：单细胞分辨率下浮游和固着细菌种群的空间转录组学发表时间：2021-08-13发表杂志：Science影响因子：47.720DOI：10.1126/science.abi4882

摘要：在相关的时空尺度上捕获微生物种群的异质表型是一项极具挑战性的工作。在这里，我们介绍了par-seqFISH（平行顺序荧光原位杂交），这是一种转录组成像方法，以单细胞和分子分辨率记录微尺度组装中的基因表达和空间背景。我们将这种方法应用于机会致病菌铜绿假单胞菌，分析了浮游生物和生物膜培养中数十种条件下的约60万个个体。我们鉴定了浮游生物生长期间动态出现的许多代谢和毒力相关的转录状态，以及固着种群中高度空间分辨的代谢异质性。我们的数据显示，不同的生理状态可以共存于几微米之外的同一生物膜中，这突出了微环境的重要性。我们的结果揭示了微生物种群的复杂动态，并提供了一种高分辨率研究微生物种群的新方法。

3英文题目：A clinically applicable integrative molecular classification of meningiomas中文题目：一种临床适用的脑膜瘤综合分子分类方法发表时间：2021-08-25发表杂志：Nature影响因子：49.962DOI：10.1038/s41586-021-03850-3

摘要：脑膜瘤是成人最常见的原发性颅内肿瘤。由于没有有效的药物治疗，出现症状的患者一般采用手术治疗。世界卫生组织肿瘤的组织病理学分级和手术切除范围(Simpson分级)与疾病复发有关；然而，它们不能准确反映所有脑膜瘤的临床表现。脑膜瘤的分子分类需要可靠地反映肿瘤行为和提供治疗信息。在这里，我们通过将DNA体拷贝数畸变、DNA体点突变、DNA甲基化和信使RNA丰度结合在一个统一的分析中，介绍了脑膜瘤的四个共有分子组。与现有的分类方案相比，这些分子组更准确地预测了临床结果。每个分子组都显示了独特的原生生物学特性(免疫原性、良性的NF2野生型、高代谢和增殖) ，为治疗选择提供了依据。蛋白质基因组特征增强了新定义分子组的稳健性，并发现了高度丰富和组特异性的蛋白靶点，我们使用免疫组化进行了验证。单细胞RNA测序揭示了脑膜瘤个体间的差异，以及肿瘤细胞内表达程序的差异，这些差异反映了所鉴定的分子组的生物学特性。

4英文题目：Clonal dynamics in early human embryogenesis inferred from somatic mutation中文题目：从体细胞突变推测人类早期胚胎发育的隆动力学发表时间：2021-08-25发表杂志：Nature影响因子：49.962DOI：10.1038/s41586-021-03786-8

摘要：由于在人类胚胎中进行研究的挑战，早期人类胚胎发生中的细胞动力学和命运决定在很大程度上仍是未知的。在这里，我们探索了334个单细胞克隆的全基因组，并针对从7个最近去世的成年人类捐赠者的不同解剖位置获得的379个块状组织的深层序列。使用体细胞突变作为内在条形码，我们重建了早期细胞系统发育，表明在第一次细胞分裂时内源性突变率较高，但在生命后期降低到大约每个细胞分裂一次；早期细胞对胚胎本身的贡献普遍不平等，这是由于早期细胞瓶颈随机地将胚胎内的外胚层细胞搁置。在身体左右两侧的组织、不同的胚层和特定的解剖部位和器官之间不同程度的早期克隆失衡的例子，出现了一些祖先细胞，它们将对血液和肝脏中的成体细胞库做出实质性贡献; 受精卵中存在线粒体DNA异质性。我们的方法也为正常体细胞中与年龄相关的突变过程和性染色体的丢失提供了见解。综上所述，本研究为完成人类胚胎发生中细胞系统发育的研究奠定了基础。

5英文题目：Whole-body integration of gene expression and single-cell morphology中文题目：基因表达和单细胞形态的整体整合发表时间：2021-08-10发表杂志：Cell影响因子：41.582DOI：10.1016/j.cell.2021.07.017

摘要：动物的身体是由具有独特表达程序的细胞类型组成的，这些细胞类型实现了它们独特的位置、形状、结构和功能。基于这些特性，细胞类型组装成特定的组织和器官。为了系统地探索细胞类型特异性基因表达与形态之间的联系，我们将表达图谱注册到圆叶藻的全身电子显微镜体积中。细胞和细胞核的自动分割识别了主要的细胞类别，并在基因激活、染色质形貌和细胞核大小之间建立了联系。根据基因表达将分裂的细胞聚类显示出空间上一致的组织。在大脑中，基因定义的神经元群与神经节核相匹配，具有一致的投射。除了中间神经元外，我们还在海棠菇体中发现了感觉神经分泌细胞，因此被称为感觉器官。在分子解剖学上，它们更类似脊椎动物的端脑。我们提供了一个集成的浏览器作为Fiji插件，用于远程探索所有可用的多模式数据集。

6英文题目：Single-cell measurement of higher-order 3D genome organization with scSPRITE中文题目：用scSPRITE进行高阶3D基因组组织的单细胞测量发表时间：2021-08-23发表杂志：Nat Biotechnol影响因子：54.908DOI：10.1038/s41587-021-00998-1

摘要：虽然三维(3D)基因组组织是核功能许多方面的核心，但很难在单细胞水平上测量。为了解决这个问题，我们开发了“通过标签扩展进行交互的单细胞分裂池识别”(scSPRITE)。scSPRITE使用split-and-pool条形码来标记同一细胞核中的DNA片段及其三维空间排列。由于scSPRITE测量的是多路DNA接触，它在单个细胞内生成的图的分辨率比近距离连接更高。我们将scSPRITE应用于数千个小鼠胚胎干细胞，检测到已知的基因组结构，包括染色体区域、活性和非活性区、拓扑关联域(TADs)以及围绕不同核体组织的长程染色体间结构。我们观察到这些结构在群体中表现出不同水平的异质性，TADs代表了细胞中基因组组织的动态单位。我们期望scSPRITE将成为研究异质群体基因组结构的关键工具。

7英文题目：Aged skeletal stem cells generate an inflammatory degenerative niche中文题目：老化的骨骼干细胞产生炎症性退行性生态位发表杂志：nature发表时间：2021-8-11影响因子：49.962DOI：10.1038/s41586-021-03795-7

摘要：衰老和疾病期间骨骼完整性的丧失与成骨细胞和破骨细胞相反作用的不平衡有关。在这里，我们表明，小鼠骨骼干细胞（SSCs）的固有老化改变了骨髓生态位中的信号传导，扭曲了骨骼和血液谱系的分化，导致脆弱的骨骼再生不良。从功能上讲，衰老的SSCs骨和软骨形成潜能降低，但产生更多的基质谱系，表达高水平的促炎症和促吸收细胞因子。单细胞RNA测序研究将功能丧失与衰老小鼠SSCs转录组多样性减少联系起来，从而有助于骨髓生态位的转化。通过异慢性副生性或年轻造血干细胞的系统重建暴露于年轻循环中，不会逆转老年SSCs骨软骨生成活性的降低，也不会改善老年小鼠的骨量或骨骼愈合参数。相反，衰老的SSCs谱系通过造血干细胞和祖细胞促进破骨细胞活性和髓样变斜，表明SSCs的老化是造血老化的驱动因素。老年小鼠骨再生不足只能通过局部应用BMP2和CSF1拮抗剂的组合治疗恢复到年轻水平，从而重新激活老年SSCs，同时清除炎症、促破骨细胞环境。我们的研究结果为骨骼老化的复杂、多因素机制提供了机制上的见解，并为老年骨骼系统的再生提供了前景。

8英文题目：Quantitative lineage analysis identifies a hepato-pancreato-biliary progenitor niche中文题目：定量谱系分析确定肝胰胆管祖细胞生态位发表杂志：nature发表时间：2021-8-25影响因子：49.962DOI：10.1038/s41586-021-03844-1

摘要：基于单细胞的研究揭示了干细胞和祖细胞间的巨大细胞异质性，表明在器官发生过程中，细胞在不同的谱系承诺状态和显著的可塑性程度下混合的持续分化轨迹。肝-胰-胆管器官系统依赖于一个小型内胚层祖细胞室，产生多种不同的成人组织，包括肝脏、胰腺、胆囊和肝外胆管。小鼠胚胎中各种发育信号的实验操作强调了这一胚胎区域的重要细胞可塑性。这反映在人类遗传综合征的存在以及肝脏、胰腺和胆囊中具有多器官表型的先天性畸形中。然而，导致内胚层祖细胞室分离为肝脏、胆道和胰腺结构的确切谱系层次和事件序列尚未确定。在这里，我们将计算建模方法与遗传谱系追踪相结合，以准确地重建肝-胰-胆管谱系树。我们发现肝-胰-胆管器官雏形中存在一个多能祖细胞亚群，不仅为胰腺和胆囊提供细胞，而且为肝脏提供细胞。此外，利用单细胞RNA测序和功能性实验，我们定义了一个特殊的生态位，在发育过程中长时间以多能状态支持该亚群。这些发现共同表明肝-胰-胆管发育的持续可塑性，这也可能解释了肝脏快速扩张同时抑制胰胆管生长的原因。

9英文题目：Spatial omics and multiplexed imaging to explore cancer biology中文题目：空间组学和多重成像探索癌症生物学。发表时间：2021-08-02发表杂志：Nature Methods影响因子：28.547DOI：10.1038/s41592-021-01203-6

摘要：了解肿瘤内异质性——肿瘤内部细胞间的分子变异——有望解决癌症生物学中的突出问题，提高对特定癌症亚型的诊断和治疗。单细胞分析，特别是RNA测序和其他基因组学模式，在揭示与肿瘤生长、转移和耐药性相关的新型生物标记物和分子调节剂方面具有革命性。然而，这些方法无法提供完整的肿瘤生物学图像，因为关于肿瘤微环境中细胞位置的信息丢失了。利用多重荧光、DNA、RNA同位素标记的新技术，可以在其天然空间环境内检测数以万计的癌症亚克隆或分子生物标志物。这些技术的迅速发展，以及多组学数据整合的方法，有望使人们更全面地了解单个肿瘤内部和之间的细胞间变异。在这里，我们提供了现有状态和未来的空间技术视角，该技术预期推动下一代癌症研究和诊断及治疗策略。

10英文题目：Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution中文题目：单细胞分辨率下发育中人类大脑皮层的染色质和基因调控动态变化发表时间：2021-08-11发表杂志：Cell影响因子：41.582DOI：10.1016/j.cell.2021.07.039

摘要：大脑皮层发育的遗传干扰可导致神经发育疾病，包括自闭症谱系障碍（ASD）。为了确定对皮层发育至关重要的基因组域，研究人员绘制了基因调控元件的活性图谱，生成了一个独立和联合的基因表达和染色质可及性的单细胞图谱。这揭示了关键转录因子（TFs）在几乎连续分化轨迹中的基因调控浪潮，区分了胶质细胞系的表达程序，并确定了决定细胞系的TFs，这些TFs在连接的基因调控元件和表达水平之间表现出强烈的相关性。这些高度关联的基因在早期分化的细胞中采用了活跃的染色质状态，与谱系定型一致。碱基分辨率的神经网络模型确定了非编码突变在自闭症谱系障碍个体队列中的强烈细胞类型特异性富集，并确定了经常被破坏的TF结合位点。这种方法说明了细胞类型特异性图谱如何能够提供对人类发育和疾病控制程序的洞察。

11英文题目：Integrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA)中文题目：通过克隆型邻域图分析(CoNGA)整合T细胞受体序列和转录谱发表时间：2021-08-23发表杂志：Nat Biotechnol影响因子：54.908DOI：10.1038/s41587-021-00989-2

摘要：T细胞克隆型(由T细胞受体(TCR)序列定义)与表型(反映在基因表达(GEX)谱、表面蛋白表达和多肽:主要组织相容性复合体结合)之间的联系，可以揭示除克隆相关细胞共享的特征之外的功能关系。在此，我们提出了克隆型邻域图分析(CoNGA)，一种通过对GEX和TCR相似性图的统计分析来识别GEX轮廓和TCR序列之间的相关性的图论方法。利用CoNGA，我们发现了TCR序列和GEX谱之间的关联，其中包括之前未描述的人类循环CD8+T细胞的“自然淋巴细胞”群体和一组胸腺细胞分化的TCR序列决定因素。这些例子表明，CoNGA可能有助于阐明大型、异质性、单细胞数据集中TCR序列和T细胞表型之间的复杂关系。

12英文题目：SnapHiC: a computational pipeline to identify chromatin loops from single-cell Hi-C data中文题目：SnapHiC:从单细胞Hi-C数据中识别染色质循环的计算管道发表时间：2021-08-26发表杂志：Nat Methods影响因子：28.547DOI：10.1038/s41592-021-01231-2

摘要：单细胞Hi-C(scHi-C)分析已经越来越多地用于绘制不同组织环境中的染色质结构，但从scHi-C数据中以高分辨率定义染色质环的计算工具仍然缺乏。在这里，我们描述了Hi-C的单核分析管道(SnapHiC)，这是一种可以从scHi-C数据中以高分辨率和准确性识别染色质环的方法。利用来自742个小鼠胚胎干细胞的scHi-C数据，我们将SnapHiC与一些用于绘制染色质环和大量Hi-C相互作用的计算工具进行基准测试。我们通过分析来自2869个人类前额叶皮质细胞的单核甲基-3C-seq数据，进一步证明它的用途，这些数据揭示了细胞类型特异性的染色质环，并预测了与神经精神疾病相关的非编码序列变异的假定靶基因。我们的研究结果表明，SnapHiC有助于对复杂组织中细胞类型特异性染色质结构和基因调控程序的分析。

13英文题目：Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children中文题目：上呼吸道预先激活的抗病毒先天免疫控制了儿童早期SARS-CoV-2感染发表时间：2021-08-18发表杂志：Nat Biotechnol影响因子：54.908DOI：10.1038/s41587-021-01037-9

摘要：与成人相比，儿童的严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)感染率降低，患2019年严重冠状病毒病的风险大大降低。然而，在较年轻的年龄组中提供保护的分子机制尚不清楚。在这里，我们描述了sars-cov-2阴性(n=18)和年龄匹配的sars-cov-2阳性(n=24)儿童和相应的成人样本(n=44)呼吸道的单细胞转录情况，年龄范围从4周至77岁。在上气道上皮细胞、巨噬细胞和树突状细胞中，儿童表现出更高的相关模式识别受体如MDA5 (IFIH1)和RIG-I (DDX58)的基础表达，导致儿童在感染SARS-CoV-2时比成人更强的先天抗病毒反应。我们进一步检测到不同的免疫细胞亚群，包括KLRC1(NKG2A)+细胞毒性T细胞和主要发生在儿童的具有记忆表型的CD8+ T细胞群。我们的研究提供了证据，表明儿童的气道免疫细胞为病毒感知做好了准备，导致对SARS-CoV-2感染的早期先天抗病毒反应比成人更强。

14英文题目：SCITO-seq: single-cell combinatorial indexed cytometry sequencing中文题目：SCITO-seq:单细胞组合索引细胞计数测序发表时间：2021-08-05发表杂志：Nat Methods影响因子：28.547DOI：10.1038/s41592-021-01222-3

摘要：用于标记细胞表面分子的dna条形码抗体的开发使得使用基于液滴的单细胞测序(dsc-seq)同时分析数千个细胞的蛋白质丰度成为可能。与流式和大规模细胞检测技术相比，目前基于dsc-seq的工作流每细胞的高成本妨碍了它们在临床应用和大规模合并筛选中的使用。在这里，我们介绍了SCITO-seq，这是一个使用夹板寡核苷酸（寡核苷酸）的工作流程，使用商业微流体对每次反应来自超过105个细胞的dna条形码抗体进行组合索引的dsc-seq。通过将样本条形码编码为夹板寡核苷酸，我们证明了多路SCITO-seq产生可重复的细胞组成和表面蛋白表达估计，与大规模细胞术的估计相当。我们进一步展示了两种改进的夹板寡核苷酸设计，它们扩展了SCITO-seq，以实现与商业dna条形码抗体的兼容性，并同时对来自同一细胞的转录组和表面蛋白进行表达谱。这些结果表明，scto -seq是一个灵活的、超高通量的单细胞蛋白测序和多模态分析平台。

15英文题目：Mapping single-cell data to reference atlases by transfer learning中文题目：通过转移学习将单细胞数据映射到参考图谱发表时间：2021-08-30发表杂志：Nat Biotechnol影响因子：54.908DOI：10.1038/s41587-021-01001-7

摘要：大型单细胞图谱现在被常规生成，作为分析小规模研究的参考。然而，由于数据集之间的批处理效应、计算资源的可用性有限和对原始数据的共享限制，从参考数据中学习变得复杂。在这里，我们介绍了一种深度学习策略，用于映射一个称为单细胞架构手术(scArches)的参考之上的查询数据集。scArches使用传输学习和参数优化，在不共享原始数据的情况下实现新数据集的高效、分散、迭代的参考构建和上下文化，而不共享原始数据。利用来自小鼠大脑、胰腺、免疫和全生物体图谱的例子，我们表明，尽管scArchs使用了比从头整合少四个数量级的参数，但在去除批效应的同时保留了生物状态信息。最后，scArches保留了2019冠状病毒病(COVID-19)的疾病变异，当映射到健康参考时，可以发现特定疾病的细胞状态。scarch将通过迭代构建、更新、共享和有效使用参考地图集来促进合作项目。

16英文题目：Reinforcing neuron extraction and spike inference in calcium imaging using deep self-supervised denoising中文题目：利用深度自监督去噪在钙成像中的神经元提取和峰推理发表时间：2021-08-16发表杂志：Nat Methods影响因子：28.547DOI：10.1038/s41592-021-01225-0

摘要：钙成像通过提供了一种以单细胞分辨率监测神经回路活动的方法，改变了神经科学研究。然而，钙成像本质上容易受到检测噪声的影响，特别是在高帧率或低激发剂量的成像时。在这里，我们开发了DeepCAD，一种用于钙成像数据时空增强的自监督深度学习方法，不需要任何高信噪比(SNR)观测。DeepCAD抑制了检测噪声，将信噪比提高了十倍以上，提高了神经元提取和尖峰推断的准确性，促进了神经回路的功能分析。

17英文题目：Identification of HSC/MPP expansion units in fetal liver by single-cell spatiotemporal transcriptomics中文题目：通过单细胞空间转录组学鉴定胎儿肝脏中的HSC/MPP扩增单位发表时间：2021-08-02发表杂志：Cell research影响因子：25.617DOI：10.1038/s41422-021-00540-7

摘要：造血干细胞和多能祖细胞（HSC/MPP）在其自然生态位内扩增的细胞和分子机制的有限知识阻碍了基于干细胞的血液恶性肿瘤治疗的应用。在此，我们构建了小鼠胎肝（FL）的时空转录组图谱，作为新调控机制的假设生成和后续实验验证的平台。单细胞转录组学显示三个转录异质性HSC/MPP亚群，其中一个富含CD93的亚群表现出增强的干细胞特性。此外，通过单细胞和空间转录组学的综合分析，我们发现了新的HSC/MPP“口袋状”单元（HSC PLUS），由小生境细胞（成肝细胞、基质细胞、内皮细胞和巨噬细胞）组成，富含生长因子。出人意料的是，巨噬细胞在HSC PLUS中的富集程度为11倍。在功能上，巨噬细胞HSC/MPP共培养试验和候选分子试验分别验证了巨噬细胞和生长因子（MDK、PTN和IGFBP5）在HSC/MPP扩增中的支持作用。最后，跨物种分析和功能验证表明，小鼠和人类FL-HSC/MPP之间存在保守的细胞间相互作用和扩增机制，但转录组特征不同。综上所述，这些结果为理解FL中HSC/MPP的发展提供了必要的资源，并对功能性HSC/MPP的体外扩增提供了新的见解。

18英文题目：Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level中文题目：大肠癌肝转移单细胞水平的时空免疫景观发表时间：2021-08-20发表杂志：Cancer discovery影响因子：39.397DOI：10.1158/2159-8290.CD-21-0316

摘要：肝转移是导致结直肠癌死亡的主要原因，表现出高度异质性和抑制性的免疫微环境。在这里，我们使用单细胞RNA测序和空间转录组学对97个匹配样本进行测序。引人注目的是，转移性微环境经历了免疫抑制细胞如MRC1+CCL18+M2样巨噬细胞的显著空间重编程。我们进一步开发了SCM代谢，一种用于量化单细胞代谢的计算管道，并观察到这些巨噬细胞具有增强的代谢活性。有趣的是，新辅助化疗可以阻断这种状态，并在反应性患者中恢复抗肿瘤免疫平衡，而非反应性患者恶化为更具抑制性的患者。我们的工作描述了转移的免疫进化，并揭示了肿瘤对新辅助化疗的反应。

19英文题目：Defining the variety of cell types in developing and adult human kidneys by single-cell RNA sequencing中文题目：通过单细胞RNA测序定义发育中和成人肾脏中的多种细胞类型发表时间：2021-08-11发表杂志：NPJ Regen Med影响因子：10.364DOI：10.1038/s41536-021-00156-w

摘要：就细胞类型的多样性而言，肾脏是最复杂的器官之一。人类肾脏的细胞复杂性尚未完全解开，而且多种祖细胞池和分化途径的存在，使这一挑战变得更加复杂。由于缺乏全面图像的研究以及在物种之间转换发现的挑战，研究人员对肾细胞类型的多样性存在分歧。为了找到人类肾脏细胞类型数量的答案，我们使用单细胞RNA测序对发育中和成人肾脏组织进行了研究，并将这些发现与单细胞RNA测序前时代的文献进行了比较。我们发现这些出版物展示了在整个发育过程中发现新细胞类型和中间细胞阶段以及复杂的分子特征和谱系途径的主要步骤。由于该技术的局限性，单细胞文献中细胞类型的多样性仍然存在差异。尽管如此，我们的分析接近了成年肾脏中 41 个已识别的肾脏谱系细胞群和 32 个非肾脏谱系的累积数量，此外当然还有更多的发现。单细胞RNA测序研究中的各种定义和标准仍然需要达成共识，例如什么是细胞类型的定义。尽管如此，这项早期研究已经证明对临床和再生医学具有重大影响，并显示出增强复杂体外肾组织生成的潜力。

20英文题目：Single Cell and Plasma RNA Sequencing for RNA Liquid Biopsy for Hepatocellular Carcinoma中文题目：用于肝细胞癌RNA液体活检的单细胞和血浆RNA测序发表时间：2021-08-31发表杂志：Clin Chem影响因子：8.327DOI：10.1093/clinchem/hvab116

摘要：背景：人血浆含有由体内多种细胞类型释放的RNA转录物。单细胞转录组学分析允许以高分辨率阐明循环RNA分子的细胞来源，并已成功用于妊娠环境。我们探索了类似方法的应用，以确定用于癌症检测的血浆RNA标记。方法：我们进行单细胞RNA测序以破译来自肝细胞癌 (HCC) 样本的单细胞的转录组谱。我们鉴定了细胞类型特异性转录物，并用于推断患有和未患有 HCC 的患者血浆 RNA 的细胞类型特异性基因特征 (CELSIG) 评分。结果：基于4个HCC肿瘤组织及其配对的相邻非肿瘤组织，鉴定出6个主要细胞群，包括肝细胞样、胆管样细胞、肌成纤维细胞、内皮细胞、淋巴样和髓样细胞群。与非 HCC 参与者（n = 49）相比，HCC 患者（n = 14）术前血浆RNA样本中肝细胞样细胞的 CELSIG 评分显著增加。在肿瘤切除术后3天内，HCC 患者血浆RNA样本中肝细胞样细胞的CELSIG评分下降。与使用血浆中ALB转录物丰度 [曲线下面积 (AUC) 0.72)] 区分患有和不患有HCC的患者的能力相比，使用CELSIG评分观察到了性能 (AUC：0.84) 的改进。通过ddPCR分析进一步验证了血浆RNA中的肝细胞特异性转录标记。肝细胞样细胞和胆管细胞的CELSIG评分随着患者的生存而变化。结论：单细胞转录组学分析和血浆RNA测序的结合代表了一种开发新的非侵入性癌症标志物的方法。IF＞9JournalImpact FactorTitleNature49.962A clinically applicable integrative molecular classification of meningiomasNature49.962Aged skeletal stem cells generate an inflammatory degenerative nicheNature49.962Clonal dynamics in early human embryogenesis inferred from somatic mutationNat Rev Immunol53.106Immune epigenomeNature49.962Molecular architecture of the developing mouse brainScience47.728Molecular 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