Coupled Biological and Mathematical Model of Neuronal P

神经元 P 的生物学和数学耦合模型

• 批准号: 7230430
• 负责人: Marit Nilsen-Hamilton
• 金额: $ 28.71万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7230430
• 关键词: Behavior; Biological; Biological Models; Biological Process; Biology; Brain; Cell Adhesion Molecules; Cell Culture System; Cells; Chemical Engineering; Chemicals; Clinical; Collaborations; Computer Simulation; Condition; Coupled; Cues; Cultured Cells; Development; Elements; Environment; Extracellular Matrix; Extracellular Matrix Proteins; Goals; Group Meetings; Individual; Knowledge; Mathematics; Modeling; Molecular; Molecular and Cellular Biology; Movement; Neuraxis; Neurons; Numbers; Organ Culture Techniques; Outcome; Pattern; Pattern Formation; Personal Satisfaction; Polymers; Population Heterogeneity; Procedures; Process; Proteins; Relative (related person); Retina; Retinal; Role; Signal Transduction; Spinal Cord; Stem cells; Surface; System; Testing; Tissues; Work; base; cell behavior; cell motility; data modeling; developmental neurobiology; extracellular; in vivo; insight; interdisciplinary approach; mathematical model; member; migration; nerve stem cell; neurotrophic factor; progenitor; relating to nervous system; repaired; response; stem

DESCRIPTION (provided by applicant): A fundamental question in biology is how development of the elaborately organized mammalian brain is orchestrated. Current knowledge suggests that the pattern formation during brain development is guided by a variety of signals including diffusible neurotrophic factors and preformed distributions of extracellular matrix proteins including adhesion molecules. The relative contributions of these elements and the number of permutations of each type of signal is unknown. To develop a better understanding of the movement and differentiation of neural stem cells (NSCs) in vivo, we propose to develop a mathematical model, using a cell culture system to provide quantitative data for the model. We will test the hypothesis that individual cells in a NSC population are diverse in their capability of responding to their environment by migration and differentiation. As a corollary to this hypothesis, we will test whether NSCs respond with different behaviors to unique combinations of signals from diffusible neurotrophic factors and preformed distributions of extracellular matrix (ECM) proteins. Based on this hypothesis, we propose the following specific aims: 1) Develop a biological model to test the role of extracellular matrix proteins and diffusible factors on NSC patterning. 2) Develop a mathematical model that can predict the outcome of perturbations in the biological model, and 3) Test the mathematical model using an organ culture system for NSC patterning. The current team is well prepared to carry out the proposed project and includes a developmental biologist, a molecular biologist, a polymer chemist, a mathematician, and a numerical modeler. Several individuals in this group have collaborated for many years and the group met and discussed this problem over the period of a year before submitting the application. This interdisciplinary approach will provide fundamental insights into the process of stem cell behavior during tissue integration.

描述(申请人提供)：生物学中的一个基本问题是如何协调精心组织的哺乳动物大脑的发育。目前的知识表明，脑发育过程中的模式形成是由多种信号引导的，包括可扩散的神经营养因子和包括黏附分子在内的预先形成的细胞外基质蛋白分布。这些元素的相对贡献和每种类型信号的排列数量是未知的。为了更好地了解神经干细胞(NSCs)在体内的运动和分化，我们建议建立一个数学模型，使用细胞培养系统为该模型提供定量数据。我们将检验这一假设，即NSC群体中的单个细胞通过迁移和分化对环境做出反应的能力是不同的。作为这一假设的推论，我们将测试神经干细胞是否以不同的行为响应来自扩散性神经营养因子和预先形成的细胞外基质(ECM)蛋白分布的信号的独特组合。基于这一假设，我们提出了以下具体目标：1)建立一个生物学模型来测试细胞外基质蛋白和扩散因子在NSC构型中的作用。2)建立一个可以预测生物模型中扰动结果的数学模型，以及3)使用用于NSC构图的器官培养系统来检验该数学模型。目前的团队已经做好了充分的准备，可以实施拟议的项目，其中包括一名发育生物学家、一名分子生物学家、一名聚合物化学家、一名数学家和一名数值模型师。这个小组中的几个人已经合作多年，在提交申请之前，小组在一年的时间里会见并讨论了这个问题。这种跨学科的方法将为干细胞在组织整合过程中的行为提供基本的见解。

项目成果

Astrocyte-derived interleukin-6 promotes specific neuronal differentiation of neural progenitor cells from adult hippocampus.

• DOI: 10.1002/jnr.22447
• 发表时间: 2010-10
• 期刊: JOURNAL OF NEUROSCIENCE RESEARCH
• 影响因子: 4.2
• 作者: Oh, Jisun;McCloskey, Michael A.;Blong, Christopher C.;Bendickson, Lee;Nilsen-Hamilton, Marit;Sakaguchi, Donald S.
• 通讯作者: Sakaguchi, Donald S.

A mathematical model for selective differentiation of neural progenitor cells on micropatterned polymer substrates.

微图案聚合物基底上神经祖细胞选择性分化的数学模型。

• DOI: 10.1016/j.mbs.2012.04.001
• 发表时间: 2012
• 期刊: Mathematical biosciences
• 影响因子: 4.3
• 作者: Howk,CoryL;Levine,HowardA;Smiley,MichaelW;Mallapragada,SuryaK;Nilsen-Hamilton,Marit;Oh,Jisun;Sakaguchi,DonaldS
• 通讯作者: Sakaguchi,DonaldS

Soluble factors from neocortical astrocytes enhance neuronal differentiation of neural progenitor cells from adult rat hippocampus on micropatterned polymer substrates.

来自新皮质星形胶质细胞的可溶性因子增强了成年大鼠海马神经祖细胞在微图案聚合物基底上的神经元分化。

• DOI: 10.1002/jbm.a.32242
• 发表时间: 2009
• 期刊: Journal of biomedical materials research. Part A
• 作者: Oh,Jisun;Recknor,JenniferB;Recknor,JustinC;Mallapragada,SuryaK;Sakaguchi,DonaldS
• 通讯作者: Sakaguchi,DonaldS

Multipotent adult hippocampal progenitor cells maintained as neurospheres favor differentiation toward glial lineages.

作为神经球维持的多能成年海马祖细胞有利于向神经胶质谱系的分化。

• DOI: 10.1002/biot.201400019
• 发表时间: 2014
• 期刊: Biotechnology journal
• 影响因子: 4.7
• 作者: Oh,Jisun;Daniels,GabrielleJ;Chiou,LawrenceS;Ye,Eun-Ah;Jeong,Yong-Seob;Sakaguchi,DonaldS
• 通讯作者: Sakaguchi,DonaldS