The Regenerative Potential of Aqp2+ Progenitor Cells
Aqp2 祖细胞的再生潜力
基本信息
- 批准号:10716327
- 负责人:
- 金额:$ 50.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2028-04-30
- 项目状态:未结题
- 来源:
- 关键词:AdultAntibodiesBehaviorCell CountCell LineageCell SeparationCellsClassificationClone CellsDataData SetDefectDevelopmentDiseaseDistal convoluted renal tubule structureDuct (organ) structureEmbryoExhibitsFemaleFoundationsFutureGenerationsHistologicHumanHuman PathologyImmuneImmunofluorescence ImmunologicIn Situ HybridizationIn VitroInheritedInjuryIntercalated CellKidneyLabelLigandsLinkMaintenanceMediatingMolecular ProfilingMusNatural regenerationOrganoidsOsmolalitiesPathway interactionsPropertyPublishingRegenerative MedicineRegulationReportingResearchSex BiasSignal TransductionSolidStainsTamoxifenTechniquesTestingTherapeuticThymidineTissuesTransitional CellUreteral obstructionUrinary tract infectionWorkanalogbiomarker identificationcell typedaughter cellextracellularimprovedin vivoinjury and repairinnovationinsightkidney cellkidney fibrosismalenotch proteinnovelnovel markerregeneration potentialregenerativerepairedself-renewalsexsingle-cell RNA sequencingstem cell biologystem cellstranscriptometranscriptome sequencingvacuolar H+-ATPasewater channel
项目摘要
Abstract
Identification of renal progenitor cells holds promise for elucidating their contribution to developmental defects
and for isolating human renal progenitor cells as a prerequisite to evaluating their therapeutic potential.
Whether an adult kidney harbors progenitor cells is a hotly debated issue. Because mammalian kidneys can
regenerate new cells following normal shedding and injury, we have published a strict definition of an adult
renal progenitor cell requiring in vivo demonstration of 1) self-renewal, 2) clonogenicity, 3) multipotency, and
participation in 4) tissue maintenance and in 5) injury repair. We have identified a subset of Aqp2+ cells that
were also positively stained with an antibody recognizing both V-ATPase subunits B1 and B2 (Aqp2+B1B2+) as
the first potential candidate that strictly meets these 5 requirements. These Aqp2+ progenitor cells (AP)
exhibited the capacity of self-renewal, clonogenicity, and multipotency, and generated 5 types of cells including
principal cells (PC) and intercalated cells (IC) to form DCT2, CNT, and CD during development. Adult AP also
possessed these capabilities and regenerated all cell types in DCT2, CNT, and CD during tissue maintenance
and after unilateral ureteral obstruction (UUO). AP express IC-selective Jag1 and PC-selective Notch1, and
mediate repair correlating with Notch activation. Others have reported marked sex bias in the transcriptome
profile of PC. All of these findings have laid a solid foundation for this project. In this proposal, we propose to
test our central hypothesis that AP possess a unique molecular signature and their regenerative potential
differs between males and females and is regulated by Jag1. The specific Aims are to identify and validate the
AP's unique molecular signature (Aim 1), to investigate the AP's regenerative potential (Aim 2) and AP's
regulation by Jag1 (Aim 3) during tissue maintenance and during UUO-induced injury repair. We will explore a
combination of cutting edge techniques/approaches including RFP-based cell sorting to enrich Aqp2+ lineage
cells, single cell RNA-Seq, Aqp2ECE/+-based lineage tracing, unbiased thymidine analog labeling, and a set of
innovative tests that have been proven to be effective for vigorously validating B1B2 as a marker of AP.
Successful completion of the project will likely 1) reinforce AP as a novel concept, which differs from what has
been reported for the proximal tubules and could shed new light into the developmental, homeostatic, and
regenerative mechanisms; 2) yield deeper insights into the differential behavior of AP vs. PC and IC; 3) identify
and validate a unique molecular signature of AP for their isolation in the future; 4) link AP-mediated repair to
Notch signaling; 5) establish both sex and Jag1 as potential regulators of AP; and 6) answer many
fundamental questions regarding the origins of PC and IC, how these cells respond to injury through Notch,
and how disruption of this pathway leads to kidney fibrosis. In short, the findings are significant for human
pathology and stem cell biology in general, and for improvement of in vitro organoid generation.
摘要
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
WENZHENG ZHANG其他文献
WENZHENG ZHANG的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('WENZHENG ZHANG', 18)}}的其他基金
A novel urinary biomarker of diabetic nephropathy
糖尿病肾病的新型尿液生物标志物
- 批准号:
9192112 - 财政年份:2015
- 资助金额:
$ 50.93万 - 项目类别:
Epigenic Control of ENaC Transcription and Sodium Transport
ENaC 转录和钠转运的表观遗传控制
- 批准号:
8247094 - 财政年份:2009
- 资助金额:
$ 50.93万 - 项目类别:
Epigenic Control of ENaC Transcription and Sodium Transport
ENaC 转录和钠转运的表观遗传控制
- 批准号:
8039130 - 财政年份:2009
- 资助金额:
$ 50.93万 - 项目类别:
Epigenic Control of ENaC Transcription and Sodium Transport
ENaC 转录和钠转运的表观遗传控制
- 批准号:
7584209 - 财政年份:2009
- 资助金额:
$ 50.93万 - 项目类别:
Epigenic Control of ENaC Transcription and Sodium Transport
ENaC 转录和钠转运的表观遗传控制
- 批准号:
8436299 - 财政年份:2009
- 资助金额:
$ 50.93万 - 项目类别:
Epigenic Control of ENaC Transcription and Sodium Transport
ENaC 转录和钠转运的表观遗传控制
- 批准号:
8535426 - 财政年份:2009
- 资助金额:
$ 50.93万 - 项目类别:
Epigenic Control of ENaC Transcription and Sodium Transport
ENaC 转录和钠转运的表观遗传控制
- 批准号:
7769494 - 财政年份:2009
- 资助金额:
$ 50.93万 - 项目类别:
相似海外基金
University of Aberdeen and Vertebrate Antibodies Limited KTP 23_24 R1
阿伯丁大学和脊椎动物抗体有限公司 KTP 23_24 R1
- 批准号:
10073243 - 财政年份:2024
- 资助金额:
$ 50.93万 - 项目类别:
Knowledge Transfer Partnership
Role of Natural Antibodies and B1 cells in Fibroproliferative Lung Disease
天然抗体和 B1 细胞在纤维增生性肺病中的作用
- 批准号:
10752129 - 财政年份:2024
- 资助金额:
$ 50.93万 - 项目类别:
CAREER: Next-generation protease inhibitor discovery with chemically diversified antibodies
职业:利用化学多样化的抗体发现下一代蛋白酶抑制剂
- 批准号:
2339201 - 财政年份:2024
- 资助金额:
$ 50.93万 - 项目类别:
Continuing Grant
Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
- 批准号:
MR/Y008693/1 - 财政年份:2024
- 资助金额:
$ 50.93万 - 项目类别:
Research Grant
Developing first-in-class aggregation-specific antibodies for a severe genetic neurological disease
开发针对严重遗传神经系统疾病的一流聚集特异性抗体
- 批准号:
10076445 - 财政年份:2023
- 资助金额:
$ 50.93万 - 项目类别:
Grant for R&D
Discovery of novel nodal antibodies in the central nervous system demyelinating diseases and elucidation of the mechanisms through an optic nerve demyelination model
发现中枢神经系统脱髓鞘疾病中的新型节点抗体并通过视神经脱髓鞘模型阐明其机制
- 批准号:
23K14783 - 财政年份:2023
- 资助金额:
$ 50.93万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of the mechanisms controlling the physicochemical properties and functions of supercharged antibodies and development of their applications
阐明控制超电荷抗体的理化性质和功能的机制及其应用开发
- 批准号:
23KJ0394 - 财政年份:2023
- 资助金额:
$ 50.93万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Role of antibodies in hepatitis E virus infection
抗体在戊型肝炎病毒感染中的作用
- 批准号:
10639161 - 财政年份:2023
- 资助金额:
$ 50.93万 - 项目类别:
Defining the protective or pathologic role of antibodies in Post-Ebola Syndrome
定义抗体在埃博拉后综合症中的保护或病理作用
- 批准号:
10752441 - 财政年份:2023
- 资助金额:
$ 50.93万 - 项目类别:
Human CMV monoclonal antibodies as therapeutics to inhibit virus infection and dissemination
人 CMV 单克隆抗体作为抑制病毒感染和传播的治疗药物
- 批准号:
10867639 - 财政年份:2023
- 资助金额:
$ 50.93万 - 项目类别:














{{item.name}}会员




