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

神经干细胞（NSCs）自然存在于成人大脑中，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为终末细胞类型之前，NSCs就有能力通过吞噬从周围环境中清除正在死亡的细胞。利用细胞培养和生物分子方法，本研究试图了解NSC吞噬死细胞是否影响其自身分化。这里假设，吞噬死亡或垂死细胞将决定NSC分化成成人细胞时所承担的命运。为了了解影响其分化潜力的因素的身份和作用，了解吞噬细胞正在对死亡细胞的哪个部分进行采样也很重要。这将通过将死细胞的不同部分喂给NSCs，然后检查分化结果来研究。了解细胞是如何形成其成熟形态的，对于我们理解所有多细胞生物是如何从一个具有发育成多种不同细胞类型能力的单一初始多能干细胞发育而来的至关重要。本研究中提出的新观点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。本研究的发现可能对其他再生或发育器官系统中祖细胞的分化有更广泛的应用。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一个使用尖端科学工具和激烈科学互动的领域的培训机会。它还将为参加旨在鼓励女性从事物理和工程等基础科学事业的暑期项目的高中生提供指导机会。

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.