EAGER: Fate-commitment of neural progenitor cells is determined by their phagocytic activity

EAGER：神经祖细胞的命运决定是由它们的吞噬活性决定的

• 批准号: 1160787
• 负责人: Jonathan Kipnis
• 金额: $ 20万
• 依托单位: University of Virginia Main Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1160787&HistoricalAwards=false
• 关键词: EAGER; Fate; commitment; neural; progenitor

Neural stem cells (NSCs) exist naturally in the adult human brain and have the potential to become multiple different types of brain cells, including neurons, astrocytes, and oligodendrocytes. The process of a NSC becoming a neuron in a mature brain is known as adult neurogenesis. Even before they have started to differentiate into their terminal cell type, NSCs have the ability to clear away cells that are dying from their surroundings by engulfment. Using cell culture and biomolecular methods this study seeks to understand whether NSC engulfment of dead cells affects their own differentiation. It is hypothesized here that the engulfment of the dead or dying cell will dictate the fate assumed by NSC when it differentiates into an adult cell. It is also important to know what part of the dying cell the engulfing cell is sampling in order to understand the identity of and effect of factors that are influencing its differentiation potential. This will be investigated by feeding different parts of dead cells to NSCs and then examining the differentiation outcomes. Understanding how a cell adopts its mature form is fundamental to our understanding of how all multicellular organisms develop from a single initial pluripotential stem cell that has the ability to develop into multiple different cell types. The novel ideas proposed in this study have the potential to shed new light on our understanding of neurogenesis in a regenerating system. Findings uncovered here could have wider application to differentiating progenitor cells in other regenerating or developing organ systems. Thus, this study will further the understanding of how all stem cells turn into their ultimate cell types. This project will provide training opportunities for post-graduate, graduate, and undergraduate students in a field that uses cutting-edge scientific tools and intense scientific interactions. It will also offer mentoring opportunities for high school students who participate in summer programs that seek to encourage women to pursue careers in basic science, including physics, and engineering.

神经干细胞（NSC）天然存在于成年人脑中，并有潜力成为多种不同类型的脑细胞，包括神经元，星形胶质细胞和少突胶质细胞。NSC在成熟大脑中成为神经元的过程被称为成人神经发生。甚至在它们开始分化成终末细胞类型之前，NSC就有能力通过吞噬清除周围死亡的细胞。利用细胞培养和生物分子方法，本研究旨在了解NSC吞噬死细胞是否影响其自身的分化。这里假设死亡或垂死细胞的吞噬将决定NSC分化为成体细胞时所承担的命运。同样重要的是要知道吞噬细胞正在对垂死细胞的哪个部分进行采样，以便了解影响其分化潜力的因素的身份和影响。这将通过将死细胞的不同部分喂给NSC，然后检查分化结果来研究。了解细胞如何采用其成熟形式对于我们了解所有多细胞生物如何从具有发育成多种不同细胞类型能力的单个初始多能干细胞发育至关重要。 这项研究中提出的新想法有可能为我们对再生系统中神经发生的理解提供新的线索。 这里揭示的发现可能有更广泛的应用，以分化祖细胞在其他再生或发展器官系统。因此，这项研究将进一步了解所有干细胞如何转变为最终的细胞类型。该项目将为研究生，研究生和本科生提供培训机会，该领域使用尖端的科学工具和激烈的科学互动。 它还将为参加暑期项目的高中生提供指导机会，这些项目旨在鼓励女性从事基础科学，包括物理学和工程学。