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Establishing a Potential and Flux Landscape Theory for Stem Cell Fate Decision Making of Differentiation and Reprograming

Establishing a Potential and Flux Landscape Theory for Stem Cell Fate Decision Making of Differentiation and Reprograming
建立干细胞分化和重编程命运决策的电位和通量景观理论
批准号:
1606549
负责人:
Jin Wang
金额:
$70.04万
依托单位:
依托单位国家:
美国
项目类别:
Continuing Grant
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-01 至 2021-08-31

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中文摘要
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英文摘要
Decision making is essential for cell functions and realized through many underlying cellular processes, such as signaling, gene regulation, the development and differentiation in viruses, bacteria, yeast, metazoans, and mammals. Understanding the cell decision making for differentiation and reprograming, the biological process from a multi-potent stem or progenitor state to a mature cell and back, is crucial not only for uncovering the underlying mechanisms but also for the practice of tissue regeneration. Despite significant efforts and progress made in this field, there are still major challenges in the stem cell fate decision making: (1) how to define the cell states and cell fates and how to uncover the physical mechanism and dynamics of decision making; (2) how to quantify the differentiation and reprograming paths for the fate decision process; (3) how to identify key factors determining the cell fates; (4) what are the effects of epigenetics, micro RNAs and cell-cell communications on differentiation and reprograming; and (5) how is the study related to the reprograming and practice of tissue regeneration. Addressing these issues is the goal of this project and specifically the quantification of the stem cell fate decision making process, which is still difficult so far due in part to the lack of a quantitative physical theory as the foundation.This project will meet these challenges through developing a physical landscape and flux theory for stem cell decision making. There are three aims. In Aim 1 the PI will develop the landscape and flux theory of stem cell differentiation and reprograming, and quantify cell states, dynamical rates, kinetic paths, and key regulations of the stem cell decision making process. In Aim 2, the PI will apply the theory to a core gene network of the stem cell differentiation in embryo development. He will further explore the mechanism of differentiation and reprograming. He will explore the effects of epigenetics through slow regulatory binding on differentiation and reprograming by modeling and experiments. In Aim 3, the PI will apply this theory to a realistic network for stem cell differentiation and reprograming involved in embryo development. He will quantify the underlying landscape topography, dynamical rates and paths, taking into consideration epigenetics, micro RNAs and cell-cell communications. He will also predict key genes and regulations for the stem cell fates and decision making process essential for reprogramming, which can be verified from experiments. This has potential applications on reprograming and tissue engineering.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Systems and Synthetic Biology Cluster in the Division of Molecular and Cellular Biosciences.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
Exploring the Underlying Mechanisms of the Xenopus laevis Embryonic Cell Cycle
探索非洲爪蟾胚胎细胞周期的潜在机制
DOI: 10.1021/acs.jpcb.7b11840
发表时间: 2018
期刊: Journal of Physical Chemistry B
影响因子: 3.3
作者: [Zhang Kun, Wang Jin]
通讯作者: Wang Jin
eMB: Collaborative Research: Fluid Dynamics and Infectious Diseases: An Integrated Modeling Framework
EAGER: A Novel Multi-Tray Dry Biofilm Reactor for Methane Capture from Air
  • 批准号:
    2331602
  • 项目类别:
    Standard Grant
  • 资助金额:
    $20.0万
  • 财政年份:
    2023
  • 负责人:
    Jin Wang
  • 依托单位:
Deterministic Models for Waterborne Infections
Collaborative Research: Consequences of Environmental Stochasticity for the Spatial Dynamics of Savanna-Forest Transitions
  • 批准号:
    1951385
  • 项目类别:
    Continuing Grant
  • 资助金额:
    $5.84万
  • 财政年份:
    2020
  • 负责人:
    Jin Wang
  • 依托单位:
国内基金
海外基金
Transient Receptor Potential 通道 A1在膀胱过度活动症发病机制中的作用
  • 批准号:
    30801141
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    28.0万元
  • 批准年份:
    2008
  • 负责人:
    都书琪
  • 依托单位: