Contribution of a novel, developmentally-restricted hematopoietic stem cell

项目摘要/摘要 分层免疫系统的概念需要产生特定的功能组件 处于不同发育阶段的免疫系统。尽管进行了30年的研究，但细胞 免疫分层的潜在机制仍然难以捉摸。我们的实验室最近发现了细胞 促进免疫分层的机制。使用一个血统追踪小鼠模型，在 在我们的实验室，我们发现了一种发育受限的造血干细胞(HSC)，它能产生 发育受限的先天免疫细胞。这些与生俱来的免疫细胞是 免疫耐受和自身免疫。在这个发现的基础上，我的研究兴趣集中在确定 免疫耐受和自身免疫建立的发育机制 敏感度。我的目标是确定这个新的造血干细胞群体在建立 发育过程中的先天免疫力。然后，我试图定义特定的表型、功能和遗传 由发育受限的HSC产生的免疫细胞的属性。最后，我的目标是确定 围产期免疫损伤对发育造血、免疫发育和自身免疫的影响 疾病易感性。这项工作将在加州大学圣诞老人分校的干细胞生物学研究所进行 克鲁兹在造血干细胞生物学专家卡米拉·福斯伯格博士的实验室里。在我的人生历程中 我在营养学方面的博士培训和在造血干细胞生物学方面的博士后培训， 在发育、分子和细胞生物学方面获得了相当大的技术和智力广度。我的 眼下的目标是扩大我在免疫学领域的培训，包括课程学习，与专家合作 加州大学旧金山分校的免疫学实验室，以及我的共同导师罗伯特·科夫曼博士的指导，他是一位著名的 先天免疫学专家。我的长期目标是建立一个创新的、独立的研究项目 发育、造血学和免疫学的接口。

PROJECT SUMMARY/ABSTRACT The concept of a layered immune system entails the generation of specific functional components of the immune system at different stages of development. Despite three decades of research, the cellular mechanisms underlying immune layering have remained elusive. Our lab recently identified the cellular mechanism contributing to immune layering. Using a lineage tracing mouse model thoroughly characterized in our laboratory, we discovered a developmentally limited hematopoietic stem (HSC) that gives rise to developmentally restricted innate-like immune cells. These innate-like immune cells are critical mediators of immune tolerance and autoimmunity. Building on this discovery, my research interests focus on determining the developmental mechanisms underlying the establishment of immune tolerance and autoimmune susceptibility. I aim to define the unique function of this novel hematopoietic stem cell population in establishing innate immunity during development. I then seek to define the specific phenotypic, functional, and genetic attribute of immune cells generated from a developmentally-restricted HSC. Lastly, I aim to determine the effect of perinatal immune insult on developmental hematopoiesis, immune development and autoimmune disease susceptibility. This work will be conducted in the Institute for the Biology of Stem Cells at UC Santa Cruz in the lab of Dr. Camilla Forsberg, an expert in hematopoietic stem cell biology. Over the course of my doctoral training in nutritional sciences and my postdoctoral training in hematopoietic stem cell biology, I have gained considerable technical and intellectual breadth in developmental, molecular, and cell biology. My immediate goal is to broaden my training within immunology, including coursework, collaboration with expert immunology labs at UC San Francisco, and guidance by my co-mentor, Dr. Robert Coffman, a renowned expert in innate immunology. My long-term goal is to establish an innovative, independent research program at the interface of development, hematopoiesis and immunology.