Early Events in Mammalian B-Cell Differentiation

描述(由申请人提供)：具体地说，这是一项请求，要求在正在进行的题为“哺乳动物B细胞分化的早期事件”的AI-20069项目中增加第三个具体目标，“研究谱系稳定性和造血方向性”。这些实验将严格测试一个新概念，即原始造血细胞可以逆转分化并重新获得一些干细胞特性。事实上，干细胞在产生血统受限的祖细胞之前，通常可能会在不同的状态之间振荡。同样的现象可能解释了恶性肿瘤保留稀有肿瘤干细胞的能力。更好地了解造血细胞的稳定性将有助于了解在正常和疾病情况下免疫系统是如何被替换的。考虑到这一概念的创新性，这些实验可能会开启一条全新的调查路线。然而，我们需要更多的人员和用品，以及生物信息学和微阵列支持，这些支持可以通过与OMRF的NCRR支持的Cobre合作获得，题为“指导文化中的科学(RR015577)”。这个科布雷在指导和网络方面有着令人自豪的记录，以及一流的核心设施。因此，本副刊将涵盖的杰出年轻研究人员将从与本科布雷的互动中受益，并为最终成为一名独立教员而受到培训。此外，家长RO1的PI将为COBRE的其他参与者提供专业知识和指导。动物模型、正常人体标本和方案都已准备就绪，可以立即使用，研究计划可以在两年内完成。 公共卫生：免疫系统中的细胞不断被驻留在骨骼中的稀有干细胞取代。人们一直认为，这只发生在一个方向上，从干细胞到血细胞。然而，令人兴奋的新发现表明，两者之间存在一定程度的反复无常。更多的研究可能会为自身免疫、恶性肿瘤和其他涉及免疫系统的疾病提供新的治疗方法。

DESCRIPTION (provided by applicant): Specifically, it is a request to add a third Specific Aim, "To study lineage stability and directionality of hematopoiesis", to an ongoing project, AI-20069, entitled "Early Events in Mammalian B-Cell Differentiation". The experiments will rigorously test a new concept, i.e. that primitive hematopoietic cells can reverse differentiation and re-acquire some stem cell properties. Indeed, stem cells may normally oscillate between states before giving rise to lineage restricted progenitors. The same phenomenon could account for the ability of malignancies to retain rare tumor stem cells. A better understanding of the stability of blood forming cells will be informative about how the immune system is replaced in normal and disease circumstances. Given the innovative nature of the concept, the experiments may open an entirely new line of investigation. However, we need additional personnel and supplies, as well as bioinformatics and microarray support that can be obtained by affiliation with OMRF's NCRR supported COBRE, entitled "Science in a Culture of Mentoring (RR015577)". This COBRE has a proud record in mentoring and networking, as well as superb Core Facilities. Thus, the outstanding young investigator to be covered by this supplement will benefit from interactions with this COBRE and be groomed for eventual status as an independent faculty member. In addition, the PI of the parent RO1 will contribute expertise and mentoring to other participants in the COBRE. Animal models, normal human specimens and protocols are all ready to be used immediately, and the research plan can be completed in two years. PUBLIC HEALTH REVELANCE: Cells in the immune system are constantly replaced from rare stem cells that reside within bones. It has always been believed that this occurs in one direction, from stem cell to blood cell. However, exciting new findings suggest there is a degree of back and forth. More study could suggest new therapies for autoimmune, malignant and other diseases involving the immune system.