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: 7448120
• 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/7448120
• 关键词: Achievement; Aorta; Biological Assay; Bone Marrow; Bone Marrow Transplantation; Boston; Cell surface; Cells; Cellular biology; Congenic Mice; Consultations; Cyclophosphamide/Doxorubicin/Etoposide/Prednisone/Vincristine; 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; Public Health; Publications; Research; Research Personnel; Role; Schools; Secure; Source; Staging; Stem Cell Research; Stem cells; Technical Expertise; Testing; Transplantation; Work; adult stem cell; base; career; cell type; embryonic stem cell; experience; in vivo; oncology; planetary Atmosphere; progenitor; programs; research study; skills

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）： 提出了一项为期5年的计划，其中候选人将成为干细胞生物学领域的独立研究者，并进一步了解我们对胚胎干细胞产生的造血干细胞（ESC-HSC）。在研究生院，候选人在成年干细胞方面发展了专业知识，重点是HSC。作为博士后，她通过研究ESC的差异化潜力来进一步探索CDX基因在ESC造血发展中的作用。目前，这项工作正在审查中。她目前的研究重点是ESC-HSC。尽管HSC最近是从ESC产生的，但对它们的表型和功能一无所知，尤其是与体内HSC有关。候选人将通过阐明ESC-HSC室内的ESC-HSC类似于在体内的发育不成熟的假说，通过通过体内移植试验中的HSC活性和分子在功能上比较这些细胞的表型，并通过对全球基因表达的微极度分析，从鼠标纯化的HSC表达进行了分子，从而在不同的Viv eviv n viv n viv n n n sevely n viv n n viv，这项工作将在波士顿儿童医院的血液学/肿瘤学分会下进行，在干细胞生物学领导者乔治·戴利博士的指导下。该部门是多个以其在干细胞研究中的成就而闻名的实验室的所在地（例如Stuart Orkin和Len Zon博士），并且是一种富裕且协作的氛围，用于促进这一领域。为了确保自己成为独立研究者并成功完成拟议的工作，候选人必须1）扩大与她的研究有关的新领域的专业知识（例如发展生物学），2）获得新的技术专长（例如胚胎解剖），以及3）发展到过渡到独立位置所需的技能（例如Grantshipship）。为此，在与主要导师进行了广泛的磋商之后，她制定了一个个性化的计划，该计划由教学和实践课程，研讨会和讲习班组成，以及经验丰富的教师委员会，她将在半隔一段时间会面，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将使候选人能够发展专业知识，以确立自己为ESC研究中的独立且竞争性的研究者。 公共卫生相关性：骨髓移植（BMT）被广泛利用用于治疗造血疾病。然而，许多患者缺乏捐助者，或者必须使用非理想的捐助者，从而导致威胁生命的并发症。可移植细胞的替代来源将大大扩展对挽救生命的程序的机会，并最大程度地减少并发症。胚胎干细胞具有生成任何细胞类型的能力，代表了一种希望得出BMT替代细胞源的希望。该提案中的工作将通过增加我们对从胚胎干细胞分离的细胞的理解来显着提高目标。