Kidney single cell and spatial molecular atlas project - KIDSSMAP

肾脏单细胞和空间分子图谱项目 - KIDSSMAP

• 批准号: 10705682
• 负责人: Tarek Maurice Ashkar
• 金额: $ 225万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705682
• 关键词: 3-Dimensional; ATAC-seq; Acids; Acute; Adult; Affect; Age; Aging; Anatomy; Atlases; Biodiversity; Biological Assay; Biology; Biomedical Engineering; Biopsy; Blood; Cell Nucleus; Cells; Cellular biology; Chromatin; Chronic; Clinical; Collaborations; Communities; Complex; Data; Data Analyses; Data Set; Dimensions; Disease; Disease Outcome; Drug Targeting; Educational Activities; Electrolyte Balance; End stage renal failure; Epigenetic Process; Equilibrium; Erythropoiesis; Ethnic Origin; Extracellular Matrix Proteins; Fluorescence Microscopy; Fostering; Gene Expression; Gene Expression Regulation; Generations; Genes; Genetic Transcription; Goals; Health; Human; Human BioMolecular Atlas Program; Image; Immune; Immunofluorescence Immunologic; Institution; Internships; Kidney; Kidney Diseases; Knowledge; Label; Life; Light; Link; Lipids; Maps; Metadata; Microscopic; Microscopy; Molecular; Molecular Biology; Molecular Structure; Nebraska; Neighborhoods; Nephrons; Nerve; Organ; Output; Oxidation-Reduction; Pathology; Pathway interactions; Patients; Persons; Phase; Physicians; Physiology; Population Heterogeneity; Process; Productivity; Proteins; RNA; Race; Raman Spectrum Analysis; Readability; Regulation; Renal function; Research Personnel; Resolution; Resources; Sampling; Scientist; Small Nuclear RNA; Sodium Chloride; Source; Structure; Students; Technology; Textbooks; Tissues; Transcript; Underrepresented Students; Vision; Water; Woman; Work; absorption; base; biobank; biological heterogeneity; blood filtration; blood pressure regulation; career; cell type; cohort; data integration; data pipeline; design; disadvantaged student; empowerment; environmental enrichment for laboratory animals; epigenome; extracellular; gain of function; genome-wide; innovation; insight; men; multimodal data; multimodality; multiple omics; neurovascular; precision medicine; sex; single cell technology; solute; tool; transcriptome; transcriptomics; water conservation

Abstract (Overall) The goal of the KIDney Single cell and Spatial Molecular Atlas Project (KIDSSMAP) is to create an anatomical and molecular “metaverse” of the human kidney. KIDSSMAP will accomplish this by generating multiscalar, multidimensional and multimodal maps of the adult non-diseased human kidney at a single cell resolution. This work will build on and extend the existing efforts of the investigative team through the first phase of HuBMAP. We will specifically focus on micro functional tissue units (FTUs) and structures that are along the cortico- medullary axis of the kidney. The technologies generating data include paired single nucleus chromatin accessibility and RNA expression (snRNA/ATAC-seq -cell type and state diversity), smFISH and DART-FISH (targeted high resolution spatial interrogation of 30-1000 transcripts), spatial transcriptomics (untargeted genome wide spatial mapping of dissociative technologies), CODEX (multiplexed spatial protein interrogation to bridge with RNA technologies and 3D IF technologies), 3D multiplexed immunofluorescence (3D IF- subcellular resolution to define neighborhoods in microFTUs), lightsheet fluorescence microscopy (LSFM- anatomical maps at mesoscale of key and 3D maps of neurovascular associations with FTUs) and Scattering Raman Spectroscopy (SRS-2D, 3D label free volumetric mapping at subcellular scale). The maps generated will define quantitative metrics of cell diversity, spatial defined neighborhoods across wide scales for different types of analytes interrogated by a diverse set of single call based and spatial technologies encompassing chromatin states, gene expression, protein, extracellular matrix, metabolites and lipids ranging from subcellular to volumetric meso and anatomic scale. These will be further augmented by characterizing biologically diverse (sex, age, race) samples. These tasks will be accomplished through a KIDney Organ Specific Project (KIDOSP) and a KIDney Data Analysis Center (KIDDAC), with their outputs, milestones and delivery to the HIVE centrally managed. KIDSSMAP is formed by the alliance of investigators who have extensive expertise in kidney tissue interrogation, spatial mapping and data integration. The investigators have a track record of contributing to large consortia such as HuBMAP and KPMP through fruitful and collaborative interactions. By mapping the human kidney with its diverse functional units at high resolution and large scale, KDSSMAP will generate a valuable resource for the community to understand kidney health and disease.

摘要（总体） KIDney单细胞和空间分子图谱项目（KIDSSMAP）的目标是创建一个解剖学模型。 和人类肾脏的分子“元宇宙”。KIDSSMAP将通过生成多标量， 在单细胞分辨率下的成人非患病人肾脏的多维和多模式图。这 工作将在调查小组现有工作的基础上继续开展，并将其扩展到HuBMAP的第一阶段。 我们将特别关注微功能组织单位（FTU）和结构，沿着皮质， 肾的髓轴。产生数据的技术包括成对的单核染色质 可及性和RNA表达（snRNA/ATAC-seq -细胞类型和状态多样性），smFISH和DART-FISH （30-1000个转录本的靶向高分辨率空间询问），空间转录组学（非靶向 解离技术的全基因组空间作图）、CODEX（多路空间蛋白质询问 与RNA技术和3D IF技术连接）、3D多重免疫荧光（3D IF- 亚细胞分辨率，以确定microFTU中的邻域），光片荧光显微镜（LSFM- 关键的中尺度解剖图和神经血管与FTU关联的3D图）和散射 拉曼光谱（SRS-2D，亚细胞尺度的3D无标记体积映射）。生成的地图 将定义细胞多样性的定量指标，空间定义的社区在宽尺度上， 通过一组不同的基于单次调用的空间技术询问的分析物类型， 染色质状态、基因表达、蛋白质、细胞外基质、代谢物和脂质， 到中观体积和解剖学尺度。这些将通过描述生物多样性来进一步增强 (sex年龄、种族）样本。这些任务将通过KIDney器官特定项目完成 （KIDOSP）和KIDney数据分析中心（KIDDAC），以及它们的产出、里程碑和向 蜂巢集中管理。KIDSSMAP是由调查人员组成的联盟，他们在以下方面拥有广泛的专业知识： 肾脏组织询问、空间映射和数据整合。调查人员有记录显示， 通过富有成效的合作互动，为HuBMAP和KPMP等大型联盟做出贡献。通过 KDSSMAP将以高分辨率和大规模绘制人类肾脏及其各种功能单位， 为社区了解肾脏健康和疾病提供了宝贵的资源。