Single Cell Chromatin Profiling in Kidney Tissue
肾脏组织中的单细胞染色质分析
基本信息
- 批准号:10373426
- 负责人:
- 金额:$ 23.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-24 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:ATAC-seqAcuteAcute Renal Failure with Renal Papillary NecrosisAddressAffectAmericanAtlasesBiological MarkersCellsChIP-seqChromatinChronic Kidney FailureClinicalCommunitiesDNA MethylationDataData SetDevelopmentDiabetes MellitusDialysis procedureDiseaseDisease ProgressionDisease modelDistalEnd stage renal failureEnhancersEpigenetic ProcessEpithelial CellsFunding OpportunitiesGene ExpressionGenesGenetic TranscriptionGenomicsHumanIndividualInjuryInjury to KidneyKidneyKidney DiseasesKidney TransplantationKnowledgeLeadLifeLocalized DiseaseMapsMediatingMetabolicMethodsModificationMolecularMorbidity - disease rateMusNatural regenerationNephronsNeptuneNucleic Acid Regulatory SequencesOrganoidsPathogenesisPopulationPrevalenceProcessPropertyProtocols documentationRare DiseasesRegulator GenesRegulatory ElementRenal functionResearchRiskSamplingSignal PathwayTechniquesTechnologyTissuesTubular formationUntranslated RNAUrineVariantbioinformatics pipelinebioinformatics toolcell typechromatin immunoprecipitationchromatin modificationdrug discoveryeffective therapyepigenomeepigenomicsfunctional restorationgene repressiongenetic variantgenome wide association studygenome-widehistone modificationhuman diseasehuman modelin uteroinjuredkidney allograftkidney biopsykidney cellmolecular phenotypemortalitynephrogenesisnew therapeutic targetnovelprecision medicinepredictive markerprogramspromoterrepairedresponseresponse to injurysingle-cell RNA sequencingtechnological innovationtooltranscriptomics
项目摘要
The function of the kidney depends on the coordinated action of multiple specialized cell types organized in a particular spatial arrangement. Progress in understanding disease pathogenesis and in developing biomarkers and therapies for kidney disease has been hindered by a lack of deep molecular phenotyping.
Tissue interrogation techniques of kidney biopsies have not changed in several decades. To advance our understanding of kidney development and disease, there is a need to develop tools to define cell-type specific molecular properties in normal kidney tissue, in response to injury, and during repair and regeneration.
While progress has been made in single cell transcriptomic analysis of kidney tissue, applying new genomic technologies to define the epigenome has lagged behind. This gap in knowledge is crucial because most disease variants associated with CKD map to distal regulatory elements, which are often cell-type specific genomic enhancers. Determining the function of these regulatory regions and their effect on gene expression is limited by lack of detailed information on the chromatin state of cells in specific nephron segments in normal and diseased human kidney tissue.
Chromatin Immunoprecipitation with sequencing (ChIP-seq), a standard method for mapping epigenetic modifications, requires significantly more starting material than is available in a kidney biopsy. Moreover, the method has high background and lacks sensitivity to be readily used for chromatin profiling of single cells. To address these challenges, this application proposes to develop novel cutting edge technological and bioinformatic tools that have not yet been deployed in the kidney, which is the major objective of this R21 funding opportunity. We will establish a protocol for single cell chromatin profiling using a recently described approach, Cleavage Under Targets and Tagmentation (CUT & Tag). We will develop a bioinformatic pipeline to analyze single cell histone modifications, define how these epigenomic features change in specific cell types in disease states, and integrate these findings with single cell transcriptomic and ATAC-seq data. These technological innovations will have the potential to catalyze new mechanistic studies in the kidney, lead to discovery of novel therapeutic targets and identify biomarkers to predict disease progression.
The technical and bioinformatic tools we develop will be broadly applicable to investigate kidney diseases in human samples, as well as disease models in mice and human organoids. Integration of genome-wide epigenetic data generated with these tools with gene expression atlases being developed for mouse and human kidneys will be extremely valuable to the research community. Because many genetic variants associated with kidney disease are localized to distal regulatory elements, the combination of transcriptomic and epigenomic data will significantly expand the power of these data sets to generate hypotheses about disease mechanisms, and make inferences about novel target genes and signaling pathways
肾脏的功能依赖于多种特化细胞类型在特定空间安排下的协调作用。由于缺乏深层分子表型,对疾病发病机制的理解以及开发肾脏疾病的生物标志物和治疗方法的进展受到阻碍。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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MICHAEL I RAUCHMAN其他文献
MICHAEL I RAUCHMAN的其他文献
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{{ truncateString('MICHAEL I RAUCHMAN', 18)}}的其他基金
Research Project 2: Molecular analysis of developing post-natal mouse kidney in health and FSGS
研究项目2:健康和FSGS中小鼠产后肾脏发育的分子分析
- 批准号:
10530271 - 财政年份:2022
- 资助金额:
$ 23.63万 - 项目类别:
Research Project 2: Molecular analysis of developing post-natal mouse kidney in health and FSGS
研究项目2:健康和FSGS中小鼠产后肾脏发育的分子分析
- 批准号:
10707966 - 财政年份:2022
- 资助金额:
$ 23.63万 - 项目类别:
Epigenetic mechanisms of gene regulation in nephron progenitor cell proliferation and differentiation
肾单位祖细胞增殖和分化基因调控的表观遗传机制
- 批准号:
10289761 - 财政年份:2021
- 资助金额:
$ 23.63万 - 项目类别:
Epigenetic mechanisms of gene regulation in nephron progenitor cell proliferation and differentiation
肾单位祖细胞增殖和分化基因调控的表观遗传机制
- 批准号:
10672271 - 财政年份:2021
- 资助金额:
$ 23.63万 - 项目类别:
Epigenetic mechanisms of gene regulation in nephron progenitor cell proliferation and differentiation
肾单位祖细胞增殖和分化基因调控的表观遗传机制
- 批准号:
10442628 - 财政年份:2021
- 资助金额:
$ 23.63万 - 项目类别:
Regulation of Nephron Progenitor Cell Self-Renewal and Differentiation
肾单位祖细胞自我更新和分化的调节
- 批准号:
9607382 - 财政年份:2018
- 资助金额:
$ 23.63万 - 项目类别:
Regulation of Nephron Progenitor Cell Self-Renewal and Differentiation
肾单位祖细胞自我更新和分化的调节
- 批准号:
9258431 - 财政年份:2014
- 资助金额:
$ 23.63万 - 项目类别:
Regulation of Nephron Progenitor Cell Self-Renewal and Differentiation
肾单位祖细胞自我更新和分化的调节
- 批准号:
8638282 - 财政年份:2014
- 资助金额:
$ 23.63万 - 项目类别:
Regulation of Nephron Progenitor Cell Self-Renewal and Differentiation
肾单位祖细胞自我更新和分化的调节
- 批准号:
8908006 - 财政年份:2014
- 资助金额:
$ 23.63万 - 项目类别:
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