Structure and Functionof Nanog in Stem Cell Pluripotency

Nanog在干细胞多能性中的结构和功能

基本信息

批准号：
10731813
负责人：
Josephine Chu Ferreon
金额：
$ 34.56万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-01 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10731813
关键词：
Adopted Aging Alleles Behavior Biochemical Biological Assay Biophysics Cancer Relapse Cells Cellular biology ChIP-seq Chromatin Chromatin Loop Communication DNA DNA Binding Dependence Development Differentiated Gene Disease Dominant-Negative Mutation Dose Elements Epiblast Epigenetic Process Fluorescence Fluorescence Recovery After Photobleaching Fluorescence Resonance Energy Transfer Funding Genes Genomics Hi-C Human In Vitro Investments Lead Link Malignant Neoplasms Mediating Microscopy Molecular Molecular Probes Mus Nature Peptides Physical condensation Play Process Property Proteins Reporting Repression Research Personnel Resistance Role Source Spectrum Analysis Stem cell pluripotency Structure System Techniques Therapeutic Time Translating Work cancer stem cell chemotherapy cofactor diagnostic biomarker efficacy evaluation embryonic stem cell fluorescence imaging fluorescence lifetime imaging fortification human embryonic stem cell implantation innovation insight novel overexpression pluripotency prevent prion-like promoter recruit self assembly self-renewal single molecule single-molecule FRET transcription factor tumor tumor growth

项目摘要

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.

项目概要 NANOG 干细胞多能性的结构和功能 NANOG 直接获得干细胞多能性我们的研究还存在相当大的差距。对 NANOG 如何协调这一过程的分子理解也更加复杂。事实上，NANOG（特别是人类 NANOG）一直是一个具有挑战性的系统研究人员已成功应用创新的荧光技术。表征 NANOG 的关键结构和功能特性本质上是一种。无序蛋白 (IDP)，具有对 NANOG 自组装和据报道，NANOG 是一个“分子中心”。与超过 100 个转录因子 (TF) 和其他蛋白质相互作用，形成合作中心多能性基因的凝聚和协调激活以及分化抑制研究人员将研究并解析 NANOG 剂量敏感性如何发挥作用。在染色质循环和转录因子、共激活因子和表观遗传调节因子的募集中的作用。将采用标准和创新结构、分子、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建立多能性的机制使用 Hi-C 3.0 和单分子荧光技术分析辅因子。探测分子元件（即 OCT4-SOX2-NANOG 三联体协同性和 KLF4 生物分子缩合）参与激活NANOG表达此外，目标将是。研究 NANOG 自抑制的分子基础最后一个目标将集中于抑制。 NANOG 稳定化和寡聚化与显性负 NANOG 肽的结合。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多能性和逆转发育衰老。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Fluorescence Lifetime Imaging Microscopy of Biomolecular Condensates.

生物分子凝聚体的荧光寿命成像显微镜。

DOI：
发表时间：
2023
期刊：
影响因子：
0
作者：
Quan, My Diem;Liao, Shih;Ferreon, Josephine C;Ferreon, Allan Chris M
通讯作者：
Ferreon, Allan Chris M

Aggregation of Disordered Proteins Associated with Neurodegeneration.

与神经变性相关的无序蛋白质的聚集。

DOI：
发表时间：
2023-02-08
期刊：
影响因子：
5.6
作者：
Tsoi, Phoebe S;Quan, My Diem;Ferreon, Josephine C;Ferreon, Allan Chris M
通讯作者：
Ferreon, Allan Chris M

Direct Single-Molecule Observation of Sequential DNA Bending Transitions by the Sox2 HMG Box.

通过 Sox2 HMG Box 直接单分子观察连续 DNA 弯曲转变。

DOI：
发表时间：
2018-12-04
期刊：
影响因子：
5.6
作者：
Moosa, Mahdi Muhammad;Tsoi, Phoebe S;Choi, Kyoung;Ferreon, Allan Chris M;Ferreon, Josephine C
通讯作者：
Ferreon, Josephine C

Electrostatic modulation of hnRNPA1 low-complexity domain liquid-liquid phase separation and aggregation.

hnRNPA1 低复杂性域液-液相分离和聚集的静电调制。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Tsoi, Phoebe S;Quan, My Diem;Choi, Kyoung;Dao, Khoa M;Ferreon, Josephine C;Ferreon, Allan Chris M
通讯作者：
Ferreon, Allan Chris M

Micropolarized to the core.

微极化至核心。