Characterization of embryonic stem cell-derived hematopoietic stem cells

胚胎干细胞来源的造血干细胞的表征

• 批准号: 7586830
• 负责人: SHANNON L MCKINNEY-FREEMAN
• 金额: $ 13.93万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7586830
• 关键词: Achievement; Aorta; Biological Assay; Bone Marrow; Bone Marrow Transplantation; Boston; Cell surface; Cells; Congenic Mice; Consultations; Data; Data Set; Derivation procedure; Development; Developmental Biology; Discrimination; Dissection; Educational workshop; Embryo; Erythroid; Erythroid Cells; Faculty; Fetal Liver; Fluorescence-Activated Cell Sorting; Future; Gene Expression; Genes; Glean; Goals; Gonadal structure; Hematology; Hematopoietic; Hematopoietic stem cells; Hemoglobin; Home environment; Laboratories; Life; Mentors; Mentorship; Mesonephric structure; Microarray Analysis; Molecular Profiling; Mus; PTPRC gene; Patients; Pattern; Pediatric Hospitals; Phenotype; Placenta; Population; Positioning Attribute; Postdoctoral Fellow; Procedures; Publications; Research; Research Personnel; Role; Schools; Secure; Source; Staging; Stem Cell Research; Technical Expertise; Testing; Transplantation; Work; adult stem cell; base; career development; cell type; embryonic stem cell; experience; in vivo; meetings; oncology; planetary Atmosphere; progenitor; programs; public health relevance; research study; skills; stem cell biology

DESCRIPTION (provided by applicant): A 5-year plan is proposed in which the candidate will establish herself as an independent investigator in Stem Cell biology and further our understanding of hematopoietic stem cells generated by embryonic stem cells (ESC-HSC). In graduate school, the candidate developed an expertise in adult stem cells, focusing on HSC. As a postdoc, she furthered her expertise by researching the differentiative potential of ESC, initially exploring the role of the Cdx genes in hematopoietic development from ESC. This work is currently under review for publication. Her current research focuses on ESC-HSC. Although HSC were recently generated from ESC, nothing is known about their phenotype and function, especially in relation to in vivo HSCs. The candidate will test the hypothesis that ESC-HSC are akin to a developmentally immature in vivo HSC compartment by elucidating the phenotype of the ESC-HSC and comparing these cells functionally, by in vivo transplantation assays of HSC activity, and molecularly, via microarray analysis of global gene expression, to HSC purified from mice at different stages of in vivo development. This work will be conducted in the Division of Hematology/Oncology at Children's Hospital Boston under the mentorship of Dr. George Daley, a leader in stem cell biology. The Division is home to multiple laboratories renowned for their achievements in stem cell research (e.g. Drs. Stuart Orkin and Len Zon) and is a rich and collaborative atmosphere for advancing this field. To secure herself as an independent investigator and successfully complete the proposed work, the candidate must 1) expand her expertise in new fields pertinent to her research (e.g. Developmental Biology), 2) acquire new technical expertise (e.g. embryo dissection), and 3) develop the skills necessary to transition to an independent position (e.g. grantsmanship). Towards this end, after extensive consultation with her primary mentor, she has developed a personalized program composed of didactic and practical coursework, seminars and workshops, and a committee of experienced faculty who will meet with her semi-annually to guide her research and career development. The execution of this program, and the research aims outlined in this proposal, will allow the candidate to develop the expertise to establish herself as an independent and competitive investigator in ESC research. PUBLIC HEALTH RELEVANCE: Bone marrow transplantation (BMT) is extensively exploited for the treatment of hematopoietic maladies. Yet, many patients lack donors or must utilize non-ideal donors, resulting in life-threatening complications. Alternative sources of transplantable cells would greatly expand access to this life-saving procedure and minimize complications. Embryonic stem cells, with their capacity to generate any cell type, represent one hope for deriving an alternative cell source for BMT. The work out-lined in this proposal will significantly advance goal by increasing our understanding of cells isolated from embryonic stem cells.

描述（由申请人提供）： 提出了一个5年计划，候选人将成为干细胞生物学的独立研究者，并进一步了解胚胎干细胞（ESC-HSC）产生的造血干细胞。在研究生院，候选人开发了成人干细胞的专业知识，专注于HSC。作为博士后，她通过研究ESC的分化潜力进一步发展了她的专业知识，最初探索了Cdx基因在ESC造血发育中的作用。这项工作目前正在审查出版。她目前的研究重点是ESC-HSC。虽然HSC最近从ESC产生，但对其表型和功能，特别是与体内HSC的关系一无所知。候选人将通过阐明ESC-HSC的表型并通过HSC活性的体内移植试验在功能上比较这些细胞，以及通过全局基因表达的微阵列分析在分子上比较从体内发育的不同阶段的小鼠中纯化的HSC，来检验ESC-HSC类似于发育不成熟的体内HSC区室的假设。这项工作将在波士顿儿童医院血液学/肿瘤学部门进行，由干细胞生物学领导者乔治戴利博士指导。该部门拥有多个以干细胞研究成就而闻名的实验室（例如Stuart Orkin博士和Len Zon博士），并为推进这一领域提供了丰富的合作氛围。为了确保自己作为一个独立的研究者，并成功地完成拟议的工作，候选人必须1）扩大她的专业知识在新的领域相关的她的研究（如发育生物学），2）获得新的技术专长（如胚胎解剖），和3）发展必要的技能过渡到一个独立的位置（如granecraft）。为此，经过与她的主要导师的广泛咨询，她制定了一个个性化的计划，包括教学和实践课程，研讨会和讲习班，以及经验丰富的教师委员会谁将与她每半年见面，以指导她的研究和职业发展。该计划的执行，以及本提案中概述的研究目标，将使候选人能够发展专业知识，以建立自己作为ESC研究中的独立和有竞争力的研究者。 公共卫生相关性：骨髓移植（BMT）被广泛用于治疗造血系统疾病。然而，许多患者缺乏供体或必须使用非理想供体，导致危及生命的并发症。可移植细胞的替代来源将极大地扩大这一挽救生命的手术的可及性，并将并发症降至最低。胚胎干细胞具有产生任何细胞类型的能力，代表了获得BMT替代细胞来源的希望之一。这项计划中所概述的工作将通过增加我们对从胚胎干细胞中分离出的细胞的理解来显著推进目标。