Reprogramming of liver cell fate by Hippo signaling
通过 Hippo 信号重新编程肝细胞命运
基本信息
- 批准号:8676791
- 负责人:
- 金额:$ 38.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-07-01 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdultBiliaryBiological AssayBiologyCell TransplantationCellsCharacteristicsDataDevelopmentGene ExpressionGenesGenetic EpistasisGoalsGrowthHepaticHepatocyteIn SituIn VitroLaboratoriesLeadLiverLiver RegenerationLiver Stem CellLiver diseasesMaintenanceMammalsMediatingModelingMolecularMusNatural regenerationNatureNormal tissue morphologyOrganOrgan SizeOrgan TransplantationOrganoidsOutcome StudyPathway interactionsPatientsPopulationProcessPropertyProteinsReporterSignal TransductionSolidStagingStem cellsStructureTestingTherapeuticTransducersTransplantationWorkbasecell typecellular targetingchromatin immunoprecipitationempoweredin vivoinsightliver cell proliferationliver transplantationmatrigelmembernotch proteinnoveloval celloverexpressionprimitive cellprogenitorpublic health relevanceresearch studyresponserestorationself-renewaltissue culturetumorigenesis
项目摘要
DESCRIPTION (provided by applicant): Liver transplantation is the second most common form of solid organ transplant with more than a quarter of listed patients expiring prior to receiving an organ. Developing a means to either stimulate liver regeneration or cultivate liver cells under tissue culture conditions could potentially abrogate the need for transplantation. While several groups have attempted to cultivate liver stem cells in the laboratory, robust conditions that could fulfill the current transplantation needs have yet to be developed. Our laboratory has made two recent discoveries that may be useful for the expansion of liver stem cells. First, we have found that changes in Hippo signaling can reprogram mature hepatocytes into cells displaying characteristics of bipotential liver progenitor cells. Hippo signaling has ben previously described as a potent growth regulator, but this finding suggests this pathway also confers increased plasticity upon differentiated cells. Secondly, we have developed culture conditions in which manipulation of Hippo signaling allows for long-term growth and enormous expansion of liver progenitors and reprogrammed hepatocytes. We propose to investigate the nature of these findings in three parts: 1) Utilize a novel Hippo reporter mouse line to determine whether endogenous Hippo activity can mark the elusive liver progenitor cell in situ. 2) Elucidate whether reprogrammed-hepatocytes contain bona fide stem cells as tested functionally in vitro and in vivo; and 3) Investigate the downstream mechanisms by which YAP reprograms hepatocytes. Completion of this project would elucidate the nature of the liver progenitor/stem cell compartment; and explore the plasticity of liver cell fate as a strategy to develop transplantable cells for transplantation.
描述(由申请人提供):肝移植是第二种最常见的实体器官移植形式,超过四分之一的上市患者在接受器官之前死亡。开发一种刺激肝再生或在组织培养条件下培养肝细胞的方法可能会消除对移植的需求。虽然有几个研究小组试图在实验室中培养肝干细胞,但尚未开发出能够满足当前移植需求的强大条件。我们的实验室最近发现了两个可能对肝脏干细胞的扩增有用的发现。首先,我们发现Hippo信号的变化可以将成熟肝细胞重编程为显示双能肝祖细胞特征的细胞。Hippo信号传导以前被描述为一种有效的生长调节剂,但这一发现表明,这种途径也赋予分化细胞增加的可塑性。其次,我们已经开发了培养条件,其中Hippo信号传导的操纵允许肝祖细胞和重编程肝细胞的长期生长和巨大扩增。我们建议从三个方面研究这些发现的本质:1)利用一种新的Hippo报告小鼠系来确定内源性Hippo活性是否可以原位标记难以捉摸的肝祖细胞。2)阐明重编程的肝细胞是否含有真正的干细胞,如在体外和体内功能测试;和3)研究雅普重编程肝细胞的下游机制。该项目的完成将阐明肝祖细胞/干细胞室的性质;并探索肝细胞命运的可塑性作为开发可移植细胞用于移植的策略。
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 }}
Fernando Camargo其他文献
Fernando Camargo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('Fernando Camargo', 18)}}的其他基金
High resolution lineage tracing of developmental hematopoiesis
发育造血的高分辨率谱系追踪
- 批准号:
10585400 - 财政年份:2023
- 资助金额:
$ 38.23万 - 项目类别:
Generation of a temporal, spatial, and molecular map of in situ hematopoiesis
生成原位造血的时间、空间和分子图
- 批准号:
10415468 - 财政年份:2022
- 资助金额:
$ 38.23万 - 项目类别:
Image guided profiling of the native HSC niche
原生 HSC 利基的图像引导分析
- 批准号:
10212380 - 财政年份:2019
- 资助金额:
$ 38.23万 - 项目类别:
Image guided profiling of the native HSC niche
原生 HSC 利基的图像引导分析
- 批准号:
10018892 - 财政年份:2019
- 资助金额:
$ 38.23万 - 项目类别:
Project 1 - Molecular and cellular determinants of hematopoietic clonal expansion
项目 1 - 造血克隆扩增的分子和细胞决定因素
- 批准号:
10641540 - 财政年份:2017
- 资助金额:
$ 38.23万 - 项目类别:
Clonal analysis of hematopoietic stem and progenitor biology in situ
造血干细胞和祖细胞生物学原位克隆分析
- 批准号:
9225236 - 财政年份:2016
- 资助金额:
$ 38.23万 - 项目类别:
Clonal analysis of hematopoietic stem and progenitor biology in situ
造血干细胞和祖细胞生物学原位克隆分析
- 批准号:
9030319 - 财政年份:2016
- 资助金额:
$ 38.23万 - 项目类别:
相似海外基金
A minimally Invasive surgical platform aGainst paNcreatIc and biliary Tract cancErs using cold atmospheric PLASMA
使用冷大气等离子体治疗胰腺癌和胆道癌的微创手术平台
- 批准号:
10106237 - 财政年份:2024
- 资助金额:
$ 38.23万 - 项目类别:
EU-Funded
Modulation of the biliary immune niche by the microbiome
微生物组对胆道免疫生态位的调节
- 批准号:
10349405 - 财政年份:2023
- 资助金额:
$ 38.23万 - 项目类别:
New Therapy for the Treatment of Primary Biliary Cholangitis.
治疗原发性胆汁性胆管炎的新疗法。
- 批准号:
10697484 - 财政年份:2023
- 资助金额:
$ 38.23万 - 项目类别:
Modeling genetic contributions to biliary atresia
模拟遗传对胆道闭锁的影响
- 批准号:
10639240 - 财政年份:2023
- 资助金额:
$ 38.23万 - 项目类别:
Development of spiral tube stent for biliary drainage
胆道引流用螺旋管支架的研制
- 批准号:
23K15054 - 财政年份:2023
- 资助金额:
$ 38.23万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Generation of hiPSC-liver orgnaoid associated with the biliary system
与胆道系统相关的 hiPSC-肝脏类器官的生成
- 批准号:
23H02967 - 财政年份:2023
- 资助金额:
$ 38.23万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Involvement and mechanism of endosomal regulatory molecule RIN3 in the development of primary biliary cholangitis
内体调节分子RIN3在原发性胆汁性胆管炎发生发展中的参与及机制
- 批准号:
23K19471 - 财政年份:2023
- 资助金额:
$ 38.23万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
Pathogenesis of refractory primary biliary cholangitis for UDCA and novel therapeutic strategies
UDCA难治性原发性胆汁性胆管炎的发病机制及新的治疗策略
- 批准号:
23K06460 - 财政年份:2023
- 资助金额:
$ 38.23万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Biological Basis of Phenotypes and Clinical Outcomes in Biliary Atresia
胆道闭锁表型和临床结果的生物学基础
- 批准号:
10824147 - 财政年份:2023
- 资助金额:
$ 38.23万 - 项目类别: