No Cell Left Behind: Using Embryoid Bodies to Understand Human Biology

不遗余力:利用胚胎体来了解人类生物学

基本信息

  • 批准号:
    10651667
  • 负责人:
  • 金额:
    $ 16.4万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-01 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

Abstract This is a revised R21 proposal submitted in response to funding opportunity announcement PA-18-867, “Novel Approaches for Relating Genetic Variation to Function and Disease”. Most of the genetic variants that are associated with disease lie within non-coding DNA and are thought to affect gene regulation. This has inspired efforts to identify variants that affect gene expression levels (eQTLs) in a wide range of adult tissues. However, most disease-associated SNPs – though they are located in putatively regulatory regions – have not been found to be eQTLs. One reason for this could be that despite large-scale efforts to map eQTLs in diverse sets of tissues (e.g, GTEx), we still have not yet examined gene regulation in the cell types or states most relevant for disease. Many human tissues and cell types, especially those that are present in early development, are inaccessible due to practical or ethical constraints. Thus, the pace of genetic discovery is fundamentally limited by access to relevant human tissues. The discovery that mature human cells can be transformed into stem cells was an important step toward solving this problem. Induced pluripotent stem cells (iPSCs) provide a renewable source of human tissue that can, in theory, develop into any cell type. In practice, however, it can take years to discover how to produce any single tissue from iPSCs using directed differentiation. At the nexus of stem cell biology and emerging single-cell technologies, there is an opportunity to generate and study many, or even most, human cell types simultaneously, all within a single dish. When grown in the proper conditions, stem cells form spontaneously differentiating organoids known as embryoid bodies (EBs). Cells within EBs differentiate asynchronously into cell types originating from all three germ layers, including pluripotent, intermediate, and mature cell types. By applying single-cell RNA-sequencing (scRNA-seq) to cells within EBs, we can jointly identify eQTLs across a multitude of cell types, all within a controlled genetic environment. The use of EBs will also allow us to observe cellular transitions and regulatory events that are not evident in static cell culture.
摘要 这是一份修订后的R21提案,是为了响应PA-18-867“小说”的资助机会公告而提交的。 将遗传变异与功能和疾病联系起来的方法。 大多数与疾病相关的遗传变异位于非编码DNA中, 影响基因调控。这激发了人们努力鉴定影响基因表达水平的变异(eQTL) 在成人组织中广泛存在。然而,大多数疾病相关的SNP-尽管它们位于 pupletin调控区-尚未发现eQTL。其中一个原因可能是,尽管 尽管我们大规模努力在不同组织中定位eQTL(例如GTEx),但我们仍然没有检测到基因 调节与疾病最相关的细胞类型或状态。许多人体组织和细胞类型,特别是 由于实际或道德上的限制,在早期发展中就存在的那些因素是无法获得的。因此 基因发现的速度从根本上受到获取相关人体组织的限制。 成熟的人类细胞可以转化为干细胞的发现,是人类向干细胞研究迈出的重要一步。 解决了这个问题。诱导多能干细胞(iPSC)提供了人类组织的可再生来源, 从理论上讲,可以发展成任何类型的细胞。然而,在实践中,可能需要数年才能发现如何生产 使用定向分化从iPSC获得任何单个组织。 在干细胞生物学和新兴的单细胞技术的联系中,有机会产生并 在同一个培养皿中同时研究多种甚至大多数人类细胞类型。当生长在适当的 在某些条件下,干细胞自发形成分化的类器官,称为胚状体(EB)。细胞 在EB中,细胞异步分化成来自所有三个胚层的细胞类型,包括 多能、中间和成熟细胞类型。通过将单细胞RNA测序(scRNA-seq)应用于细胞, 在EBs中,我们可以联合鉴定多种细胞类型的eQTL,所有这些都在一个受控的遗传内, 环境EB的使用还将使我们能够观察细胞的转换和调节事件, 在静态细胞培养中明显。

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 }}

Yoav Gilad其他文献

Yoav Gilad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('Yoav Gilad', 18)}}的其他基金

No Cell Left Behind: Using Embryoid Bodies to Understand Human Biology
不遗余力:利用胚胎体来了解人类生物学
  • 批准号:
    10427990
  • 财政年份:
    2022
  • 资助金额:
    $ 16.4万
  • 项目类别:
Development of iPSCs for comparative genomics in primates
灵长类动物比较基因组学 iPSC 的开发
  • 批准号:
    10514213
  • 财政年份:
    2021
  • 资助金额:
    $ 16.4万
  • 项目类别:
Characterizing and Understanding Variation in Gene Regulatory Mechanisms Within and Between Species'
表征和理解物种内部和物种之间基因调控机制的变异
  • 批准号:
    10405511
  • 财政年份:
    2019
  • 资助金额:
    $ 16.4万
  • 项目类别:
Development of iPSCs for comparative genomics in primates
灵长类动物比较基因组学 iPSC 的开发
  • 批准号:
    10005952
  • 财政年份:
    2019
  • 资助金额:
    $ 16.4万
  • 项目类别:
Characterizing and Understanding Variation in Gene Regulatory Mechanisms Within and Between Species'
表征和理解物种内部和物种之间基因调控机制的变异
  • 批准号:
    10626752
  • 财政年份:
    2019
  • 资助金额:
    $ 16.4万
  • 项目类别:
Development of iPSCs for comparative genomics in primates
灵长类动物比较基因组学 iPSC 的开发
  • 批准号:
    10428553
  • 财政年份:
    2019
  • 资助金额:
    $ 16.4万
  • 项目类别:
Development of iPSCs for comparative genomics in primates
灵长类动物比较基因组学 iPSC 的开发
  • 批准号:
    10189681
  • 财政年份:
    2019
  • 资助金额:
    $ 16.4万
  • 项目类别:
Characterizing and Understanding Variation in Gene Regulatory Mechanisms Within and Between Species'
表征和理解物种内部和物种之间基因调控机制的变异
  • 批准号:
    10166610
  • 财政年份:
    2019
  • 资助金额:
    $ 16.4万
  • 项目类别:
Development of iPSCs for comparative genomics in primates
灵长类动物比较基因组学 iPSC 的开发
  • 批准号:
    10655911
  • 财政年份:
    2019
  • 资助金额:
    $ 16.4万
  • 项目类别:
Mapping eQTLs that affect susceptibility to Tuberculosis
绘制影响结核病易感性的 eQTL
  • 批准号:
    8207896
  • 财政年份:
    2011
  • 资助金额:
    $ 16.4万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 16.4万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 16.4万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 16.4万
  • 项目类别:
    Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 16.4万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 16.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 16.4万
  • 项目类别:
    Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
  • 批准号:
    10065645
  • 财政年份:
    2023
  • 资助金额:
    $ 16.4万
  • 项目类别:
    Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 16.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 16.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 16.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了