「领域快报」是AiBrain筹备的特别栏目,是由海内外知名高校的一线青年科研工作者(博士后、PI)精选的领域科研动态,旨在为学科融合、交叉合作提供平台和机遇。
「领域快报」RNA测序
Science
人脑血管系统的转录图谱在正常和AVM组织中的比较
Science (IF 47.73)
来自加州大学旧金山分校的研究人员在最近的《科学》杂志上比较了正常和动静脉畸形(AVM)症的人脑血管系统的单细胞转录图谱,为之后研究脑血管疾病的治疗方案提供了重要依据。
大脑血管系统是支持正常脑功能的关键,而脑血管疾病会导致神经疾病甚至死亡。AVM作为一种脑血管疾病,是年轻人群脑中风的重要病因。作者对手术中切除的正常人脑血管组织和AVM组织,分别做单细胞mRNA测序,进行比较后发现,AVM组织的血管内皮和免疫细胞的基因表达模式异常,两者相互作用,从而引发AVM病灶的多种炎症反应。
关键词:
神经科学技术与方法(RNA测序)
文章链接 :
https://www.science.org/doi/10.1126/science.abi7377
Abstract
Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of cerebrovascular cells in humans. We profiled transcriptomes of 181,388 cells to define a cell atlas of the adult human cerebrovasculature, including endothelial cell molecular signatures with arteriovenous segmentation and expanded perivascular cell diversity. By leveraging this reference, we investigated cellular and molecular perturbations in brain arteriovenous malformations, which are a leading cause of stroke in young people, and identified pathologic endothelial transformations with abnormal vascular patterning and the ontology of vascularly derived inflammation. We illustrate the interplay between vascular and immune cells that contributes to brain hemorrhage and catalog opportunities for targeting angiogenic and inflammatory programs in vascular malformations.
Nature
人和小鼠白色脂肪组织的转录图谱比较
Nature (IF 49.96)
白色脂肪组织(WAT)广泛参与多种生理功能。来自美国贝斯以色列女执事医疗中心的研究人员在《自然》发表了人WAT的转录图谱,并与模式动物小鼠的WAT转录图谱做了详细比较。
由于脂肪细胞大而易损的特性,传统单细胞测序技术无法获取完整细胞。本文作者综合运用了两种测序方法以获得人WAT的全部细胞类型:1)从皮下WAT中提取非脂肪细胞的血管基质组分(SVF)做单细胞测序(scRNA-seq);2)为得到脂肪细胞的测序,提取皮下(SAT)和内脏(VAT)脂肪组织做单细胞核测序(sNuc-seq)。为比较人和小鼠WAT的转录图谱,作者分别在正常和高脂膳食小鼠上提取腹股沟脂肪组织(ING,对应人SAT)和生殖腺旁脂肪组织(PG,对应人VAT)做sNuc-seq。
基于测序结果,作者分别识别了WAT包含的4大类细胞:脂肪细胞、脂肪干细胞和祖细胞(ASPCs)、血管细胞和免疫细胞各自的亚型,并分析了它们在不同身体部位、不同物种、不同膳食条件下转录水平的同质性和异质性。WAT结构和功能异常与多种疾病相关,因此文章分析了不同脂肪组织细胞之间的相互作用,识别了可能与代谢疾病相关的细胞类型。本文提供的人和小鼠WAT转录图谱及比较是研究WAT功能和相关疾病的重要依据。
关键词:
Fat metabolism;obesity
文章链接 :
https://www.nature.com/articles/s41586-022-04518-2
Abstract
White adipose tissue, once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic and heterogenous, and is involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control and host defence. High-fat feeding and other metabolic stressors cause marked changes in adipose morphology, physiology and cellular composition, and alterations in adiposity are associated with insulin resistance, dyslipidemia and type 2 diabetes. Here we provide detailed cellular atlases of human and mouse subcutaneous and visceral white fat at single-cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells, vascular and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease and provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits and cell types in the function of white adipose tissue across species, depots and nutritional conditions.
Science
完整果蝇的单细胞转录图谱数据库
Science (IF 47.73)
果绳是生物学研究极其重要的动物模型之一,结合多种当前非常成熟的RNA测序技术,作者对整个成年果绳身体进行单细胞测序,获得了果绳细胞图谱(FCA)数据库。作者首先分别提取了雌雄两性的12种组织和3种性别特异性组织,做单细胞核转录RNA测序(snRNA-seq),并针对两个特殊的细胞类型:胰岛素分泌细胞和心脏CC(corpora cardiaca)细胞,做Smart-Seq2测序,从而得到覆盖全身不同组织的580,000个细胞。来自全世界的40个实验室的科研人员参与了随后的注释工作,标注了与FlyBase数据库对应的251种细胞类型,并与对果绳整个头部和躯干分别做snRNA-seq的结果进行对应。在以上测序结果基础上,作者分别做了常见细胞类型的跨组织分析、转录因子的多效性和特异性分析、性别偏好的基因表达和性别特异组织的谱系分析等等,为后续研究提供了很多重要的工作点。
随着测序技术的不断成熟和成本降低,近年来科学界一直在致力于提供不同模式动物的单细胞转录图谱数据库,已经完成的包括完整成年线虫、小鼠部分组织和人的部分组织。本篇文章发表了来自多个国家研究组组成的联合团队的成果,为科学界提供了又一模式动物——果绳的完整转录图谱,并与已有果绳数据库相关联,是十分重要的免费科学资源。
文章链接 :
https://www.science.org/doi/10.1126/science.abk2432
Abstract
For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae, that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type–related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution.
Nature Biotechnology
空间转录组学新技术:Cell2location
Nature Biotechnology (IF 54.908)
如何在RNA测序基础上还原细胞的空间位置结构是空间转录组学的技术关键,来自伦敦维康桑格研究所和欧洲分子生物实验室的研究团队提出了一种被称为Cell2location的新技术,发表于2022年1月的《自然•生物技术》上。
Cell2location基于贝叶斯模型,引入统计强度理论,将单细胞RNA测序(scRNA-seq)或单细胞核RNA测序(snRNA-seq)结果与空间转录组学数据做整合,能弥补不同测序批次间的差异,评估绝对的细胞类型富集度。通过对小鼠大脑、人淋巴结和人肠道3种不同组织的应用,作者展示了Cell2location相比其它现有方法,具有更高的分辨率和灵敏度,更广泛地适用于多种生物组织和复杂的实验设计。
文章链接 :
https://www.nature.com/articles/s41587-021-01139-4#Abs1
Abstract
Spatial transcriptomic technologies promise to resolve cellular wiring diagrams of tissues in health and disease, but comprehensive mapping of cell types in situ remains a challenge. Here we present сell2location, a Bayesian model that can resolve fine-grained cell types in spatial transcriptomic data and create comprehensive cellular maps of diverse tissues. Cell2location accounts for technical sources of variation and borrows statistical strength across locations, thereby enabling the integration of single-cell and spatial transcriptomics with higher sensitivity and resolution than existing tools. We assessed cell2location in three different tissues and show improved mapping of fine-grained cell types. In the mouse brain, we discovered fine regional astrocyte subtypes across the thalamus and hypothalamus. In the human lymph node, we spatially mapped a rare pre-germinal center B cell population. In the human gut, we resolved fine immune cell populations in lymphoid follicles. Collectively, our results present сell2location as a versatile analysis tool for mapping tissue architectures in a comprehensive manner.
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