Contributio of a novel developmentally-restricted hematopoietic stem cell

新型发育受限造血干细胞的贡献

• 批准号: 9753330
• 负责人: Anna E. Beaudin
• 金额: $ 17.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, MERCED
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2020-03-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753330
• 关键词: Adult; Affect; Autoimmune Diseases; Autoimmune Process; Autoimmunity; B-Lymphocytes; Biological Response Modifiers; Cell surface; Cells; Cellular biology; Code; Collaborations; Data; Development; Developmental Biology; Disease; Disease susceptibility; Early Intervention; Epidemiology; Excision; Fetal Development; Gene Expression; Generations; Genetic; Goals; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Immune; Immune System Diseases; Immune Tolerance; Immune system; Immunity; Immunoglobulins; Immunology; Institutes; Label; Laboratories; Life; Lymphocyte; Lymphoid; Lymphoid Cell; Mediating; Mentors; Modeling; Molecular; Molecular Biology; Natural Immunity; Nutritional Science; Pathologic; Perinatal; Phenotype; Play; Populations at Risk; Predisposition; Prevention; Production; Property; Research; Role; San Francisco; Self Tolerance; T-Lymphocyte; Testing; Tomatoes; Training; Vaccination; Work; base; fetal; genome-wide; immune activation; immune function; innovation; interest; mouse model; neonatal infection; novel; post-doctoral training; programs; response; stem; stem cell biology; stem cell population

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.

项目摘要/摘要 分层免疫系统的概念需要产生 免疫系统处于不同发展阶段。尽管进行了三十年的研究，但细胞 免疫分层的基础机制仍然难以捉摸。我们的实验室最近确定了细胞 有助于免疫分层的机制。使用谱系追踪小鼠模型在 我们的实验室，我们发现了一个发育有限的造血茎（HSC），这引起了 开发限制了先天性的免疫细胞。这些先天的免疫细胞是关键的介体 免疫耐受性和自身免疫性。在这一发现的基础上，我的研究兴趣着重于确定 建立免疫耐受性和自身免疫性的发展机制 敏感性。我的目的是定义这种新型造血干细胞种群的独特功能 开发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 由发育限制的HSC产生的免疫细胞的属性。最后，我的目的是确定 围产期免疫侮辱对发育性造血，免疫发育和自身免疫的影响 疾病的敏感性。这项工作将在加州大学圣诞老人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（Camilla Forsberg）的实验室中。在我的过程中 营养科学的博士培训和我在造血干细胞生物学方面的博士后培训，我有 在发育，分子和细胞生物学中获得了相当大的技术和智力广度。我的 即时目标是扩大我在免疫学中的培训，包括课程，与专家合作 加州大学旧金山分校的免疫学实验室，以及我的同事罗伯特·科夫曼（Robert Coffman）的指导 先天免疫学专家。我的长期目标是在 发育，造血和免疫学的界面。