Structure and Functionof Nanog in Stem Cell Pluripotency
Structure and Functionof Nanog in Stem Cell Pluripotency
批准号:
10731813
负责人:
Josephine Chu Ferreon
金额:
$34.56万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
未结题
起止时间:
2018-01-01 至 2027-05-31
关键词:
AdoptedAgingAllelesBehaviorBiochemicalBiological AssayBiophysicsCancer RelapseCellsCellular biologyChIP-seqChromatinChromatin LoopCommunicationDNADNA BindingDependenceDevelopmentDifferentiated GeneDiseaseDominant-Negative MutationDoseElementsEpiblastEpigenetic ProcessFluorescenceFluorescence Recovery After PhotobleachingFluorescence Resonance Energy TransferFundingGenesGenomicsHi-CHumanIn VitroInvestmentsLeadLinkMalignant NeoplasmsMediatingMicroscopyMolecularMolecular ProbesMusNaturePeptidesPhysical condensationPlayProcessPropertyProteinsReportingRepressionResearch PersonnelResistanceRoleSourceSpectrum AnalysisStem cell pluripotencyStructureSystemTechniquesTherapeuticTimeTranslatingWorkcancer stem cellchemotherapycofactordiagnostic biomarkerefficacy evaluationembryonic stem cellfluorescence imagingfluorescence lifetime imagingfortificationhuman embryonic stem cellimplantationinnovationinsightnoveloverexpressionpluripotencypreventprion-likepromoterrecruitself assemblyself-renewalsingle moleculesingle-molecule FRETtranscription factortumortumor growth
中文摘要
项目摘要
干细胞多能性中的Nanog结构与功能
Nanog指导人们获得干细胞的多能性。我们有相当大的差距
对NANOG如何协调这一过程的分子理解。这一点还会因为
NANOG(尤其是人类NANOG)一直是一个具有挑战性的系统
和.。研究人员成功地将创新的荧光技术应用于
描述NANOG的关键结构和功能特性。Nanog是一种本质上的
无序蛋白(IDP),其具有一个Pron样结构域,对NANOG自组装和
在多潜能特定地区建立联系。Nanog是一个“分子枢纽”,据报道
与>;100转录因子(TF)和其他蛋白质相互作用形成协同中心
凝聚和协调多能基因的激活和分化的抑制
基因。调查人员将调查和揭开NANOG剂量敏感性是如何发挥作用的
在染色质循环和募集转录因子、共激活因子和表观遗传调节因子中的作用。他们
将使用标准和创新的结构、分子、
基因组和细胞生物学方法。第一个目标是阐明NANOG的剂量敏感性
通过评估染色质重组和招募来建立多能性的机制
使用Hi-C 3.0和单分子荧光技术对辅因子进行分析。第二个目标是
探索分子元素(即OCT4-SOX2-NANOG三联体协同作用和KLF4
生物分子缩合)参与激活NANOG的表达。此外,目标将是
研究NANOG自阻抗的分子基础。最后一个目标将集中在抑制上
NANOG稳定和以负性NANOG为主的多肽的齐聚。
这些研究将为NANOG如何协调建立提供前所未有的见解
干细胞的多能性和逆转发育衰老。
英文摘要
Project Summary
NANOG Structure and Function in Stem Cell Pluripotency
NANOG directs access to stem cell pluripotency. There are considerable gaps in our
molecular understanding of how NANOG coordinates this process. This is also compounded by
the fact that NANOG (in particular, human NANOG) has been a challenging system to work
with. The investigators have successfully applied innovative fluorescence techniques to
characterize NANOG’s key structure and functional properties. NANOG is an intrinsically
disordered protein (IDP), with a prion-like domain critical for NANOG self-assembly and for
establishing contacts in pluripotency specific regions. NANOG is a ‘molecular hub’, reported to
interact with >100 transcription factors (TFs) and other proteins to form cooperative hub
condensates and coordinate activation of pluripotency genes and repression of differentiation
genes. The investigators will investigate and deconvolute how NANOG dose-sensitivity play a
role in chromatin looping and recruitment of TFs, co-activators, and epigenetic regulators. They
will use an intensive holistic combination of standard and innovative structural, molecular,
genomic and cell biology approaches. The first aim will elucidate NANOG’s dose-sensitivity
mechanism in establishing pluripotency by assessing chromatin reorganization and recruitment
of cofactors using Hi-C 3.0 and single molecule fluorescence techniques. The second aim will
probe the molecular elements (i.e., OCT4-SOX2-NANOG triad cooperativity and KLF4
biomolecular condensation) involved in activating NANOG expression. In addition, the aim will
investigate the molecular basis for NANOG autorepression. The last aim will focus on inhibition
of NANOG stabilization and oligomerization with dominant negative NANOG-based peptides.
These studies will provide unprecedented insights into how NANOG orchestrates establishment
of stem cell pluripotency and reversal of developmental aging.
期刊论文(7)
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DOI:
10.3390/ijms24043380
发表时间:
2023-02-08
期刊:
International journal of molecular sciences
影响因子:
5.6
作者:
[]
通讯作者:
Micropolarized to the core.
微极化至核心。
DOI:
10.1038/s41589-024-01542-3
发表时间:
2024
期刊:
Nature chemical biology
影响因子:
14.8
作者:
[Quan,MyDiem, Ferreon,JosephineC, Ferreon,AllanChrisM]
通讯作者:
Ferreon,AllanChrisM
DOI:
10.1007/978-1-0716-2663-4_6
发表时间:
2023
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
--
作者:
[]
通讯作者:
DOI:
10.1021/acs.jmedchem.0c02070
发表时间:
2021-03-11
期刊:
Journal of medicinal chemistry
影响因子:
7.3
作者:
[Nie S, Yao Y, Wu F, Wu X, Zhao J, Hua Y, Wu J, Huo T, Lin YL, Kneubehl AR, Vogt MB, Ferreon J, Rico-Hesse R, Song Y]
通讯作者:
Song Y
NANOG prion-like assembly mediates DNA bridging to facilitate chromatin reorganization and activation of pluripotency.
Nanog Prion样装配介导DNA桥接,以促进染色质重组和多能的激活。
DOI:
10.1038/s41556-022-00896-x
发表时间:
2022-05
期刊:
Nature cell biology
影响因子:
21.3
作者:
[]
通讯作者:
Customized and Integrated Multi-Angle Light Scattering (MALS)-based Multidetection System
-
批准号:10415734
-
项目类别:
-
资助金额:$33.48万
-
财政年份:2022
-
负责人:Josephine Chu Ferreon
-
依托单位:
NANOG STRUCTURE AND FUNCTION IN STEM CELL PLURIPOTENCY
-
批准号:9814562
-
项目类别:
-
资助金额:$5.61万
-
财政年份:2018
-
负责人:Josephine Chu Ferreon
-
依托单位:
NANOG STRUCTURE AND FUNCTION IN STEM CELL PLURIPOTENCY
-
批准号:10387985
-
项目类别:
-
资助金额:$19.98万
-
财政年份:2018
-
负责人:Josephine Chu Ferreon
-
依托单位:
NANOG STRUCTURE AND FUNCTION IN STEM CELL PLURIPOTENCY
-
批准号:10084297
-
项目类别:
-
资助金额:$31.7万
-
财政年份:2018
-
负责人:Josephine Chu Ferreon
-
依托单位:
NANOG STRUCTURE AND FUNCTION IN STEM CELL PLURIPOTENCY
-
批准号:10318174
-
项目类别:
-
资助金额:$31.7万
-
财政年份:2018
-
负责人:Josephine Chu Ferreon
-
依托单位:
海外基金