A public resource of single cell transcriptomes and multiscale networks from persons with and without Alzheimer's disease.
A public resource of single cell transcriptomes and multiscale networks from persons with and without Alzheimer's disease.
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来自阿尔茨海默病患者和非阿尔茨海默病患者的单细胞转录组和多尺度网络的公共资源。
DOI：
10.1101/2023.10.20.563319
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Mast
中科院分区：
文献类型：
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作者：
Wang,Qi;Antone,Jerry;Alsop,Eric;Reiman,Rebecca;Funk,Cory;Bendl,Jaroslav;Dudley,JoelT;Liang,WinnieS;Karr,TimothyL;Roussos,Panos;Bennett,DavidA;DeJager,PhilipL;Serrano,GeidyE;Beach,ThomasG;Keuren-Jensen,KendallVan;Mast
能够支持单细胞转录组的高通量分析的技术的出现提供了对患有和没有阿尔茨海默病（AD）的人的脑组织的研究的革命性改变。这些数据与遗传学、蛋白质组学和临床数据等额外的互补多组学数据的整合提供了在更广泛的疾病相关背景下将观察到的细胞亚群和分子网络特征联系起来的强大机会。我们在这里报告的单核RNA测序（snRNA-seq）的配置文件产生的上级额回皮质组织样本，从101个非常好的特点，老年受试者从班纳大脑和身体捐赠计划结合全基因组序列。我们报告的发现将常见的AD风险变异与少突胶质细胞中CR 1的表达以及外周血液学实验室参数的改变联系起来，这些观察结果在一项独立的前瞻性队列研究中重复。我们还观察到AD相关的CD 83（+）小胶质细胞亚型具有独特的分子网络，包括许多已知的AD相关小胶质细胞生物学调节因子，并与横结肠中免疫球蛋白IgG 4的产生相关。这些发现说明了多组织分子谱分析在snRNA-seq脑转录组学中的作用，并揭示了新的疾病生物学。本研究中描述的转录组学、遗传学、表型和网络数据资源可供科学界访问和利用。
The emergence of technologies that can support high-throughput profiling of single cell transcriptomes offers to revolutionize the study of brain tissue from persons with and without Alzheimer’s disease (AD). Integration of these data with additional complementary multiomics data such as genetics, proteomics and clinical data provides powerful opportunities to link observed cell subpopulations and molecular network features within a broader disease-relevant context. We report here single nucleus RNA sequencing (snRNA-seq) profiles generated from superior frontal gyrus cortical tissue samples from 101 exceptionally well characterized, aged subjects from the Banner Brain and Body Donation Program in combination with whole genome sequences. We report findings that link common AD risk variants withCR1expression in oligodendrocytes as well as alterations in peripheral hematological lab parameters, with these observations replicated in an independent, prospective cohort study of ageing and dementia. We also observed an AD-associated CD83(+) microglial subtype with unique molecular networks that encompass many known regulators of AD-relevant microglial biology, and which are associated with immunoglobulin IgG4 production in the transverse colon. These findings illustrate the power of multi-tissue molecular profiling to contextualize snRNA-seq brain transcriptomics and reveal novel disease biology. The transcriptomic, genetic, phenotypic, and network data resources described within this study are available for access and utilization by the scientific community.