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: 10531099
• 负责人: Sanjay Jain
• 金额: $ 200万
• 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/10531099
• 关键词: 3-Dimensional; APRIN gene; ATAC-seq; Address; Adult; Affect; Age; Aging; Agreement; Anatomy; Antibodies; Antigens; Area; Atlases; Award; Biological; Biological Assay; Biology; Biopsy; Blood; Budgets; Calibration; Cell Communication; Cell Nucleus; Cells; Cellular Structures; Chromatin; Classification; Collaborations; Communities; Complex; Data; Data Analyses; Data Collection; Data Set; Detection; Dimensions; Disease; Dissection; Drops; Duct (organ) structure; Engineering; Ensure; Epithelium; Experimental Designs; Extracellular Domain; Extracellular Matrix; Feedback; Fibroblasts; Fishes; Fluorescence; Fluorescence Microscopy; Foundations; Funding; Future; Gene Expression; Gene Expression Regulation; Generations; Genetic Transcription; Goals; Graph; Health; Histology; Human; Human BioMolecular Atlas Program; Image; Imaging technology; Immune; Immunofluorescence Immunologic; In Situ; Individual; Industry Standard; Joints; Kidney; Label; Lasers; Light; Link; Lipids; Machine Learning; Manuals; Maps; Metadata; Methods; Microscopy; Minor; Modality; Molecular; Molecular Profiling; Morphology; Neighborhoods; Nephrons; Nerve; Normalcy; Organ; Output; Paper; Participant; Pathologist; Pathway interactions; Patient Recruitments; Patients; Phase; Population; Population Heterogeneity; Process; Production; Proteins; Proteome; Proteomics; Protocols documentation; Published Comment; Publishing; RNA; Race; Raman Spectrum Analysis; Readability; Regulation; Renal function; Research Personnel; Resolution; Resources; Rest; Route; Sample Size; Sampling; Scheme; Selection Criteria; Site; Slice; Slide; Small Nuclear RNA; Spottings; Stains; Standardization; Structure; Students; Supervision; Technology; Testing; Three-Dimensional Image; Time; Tissue Banks; Tissue imaging; Tissues; Training; Transcript; United States National Institutes of Health; Update; Validation; Variant; Visualization software; Work; base; cell type; confocal imaging; cost; cost effective; data integration; density; epigenomics; extracellular; genome-wide; high dimensionality; innovation; insight; instrument; interest; interoperability; kidney biopsy; kidney cell; lipidomics; machine learning algorithm; metabolomics; movie; multimodality; multiple omics; neurovascular; next generation; novel; preservation; protein biomarkers; protein metabolite; response; sex; single cell analysis; spatial integration; spectroscopic imaging; summer program; synergism; timeline; tool; tool development; transcriptome sequencing; transcriptomics; user-friendly

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) 肾脏单细胞和空间分子图谱计划(KIDSSMAP)的目标是创建一个解剖学的 和人类肾脏的分子“化身”。KIDSSMAP将通过生成多标量、 单个细胞分辨率的成人未患病人类肾脏的多维和多模式图谱。这 这项工作将在调查小组通过HuBMAP第一阶段进行的现有工作的基础上再接再厉。 我们将特别关注沿皮质的微功能组织单位(FTU)和结构- 肾脏的髓质轴。产生数据的技术包括配对的单核染色质 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份文字记录的定向高分辨率空间询问)、空间转录(非定向 解离技术的全基因组空间图谱)、CODEX(多路空间蛋白质询问 与RNA技术和3D IF技术架起桥梁)、3D多路免疫荧光(3D IF- 在MicroFTU中定义邻域的亚细胞分辨率)、光片荧光显微镜(LSFM- 关键中尺度解剖图和神经血管与FTU相关的3D图)和散射 拉曼光谱(SRS-2D，亚细胞尺度的3D无标记体积测绘)。生成的地图 将定义细胞多样性的量化指标，在大范围内为不同的 通过一组不同的基于单一呼叫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 到体积中观和解剖尺度。这些将通过描述生物多样性的特征来进一步加强 (性别、年龄、种族)样本。这些任务将通过肾脏器官特定项目来完成 (KIDOSP)和一个肾脏数据分析中心(KIDDAC)及其产出、里程碑和交付给 蜂巢集中管理。KIDSSMAP是由拥有广泛专业知识的调查人员组成的联盟 肾组织查询、空间标测和数据集成。调查人员有记录表明 通过卓有成效的协作互动，为HuBMAP和KPMP等大型财团做出贡献。通过 KDSSMAP将以高分辨率和大比例尺绘制人类肾脏及其不同功能单元的地图 为社区了解肾脏健康和疾病提供有价值的资源。