Early Events in Mammalian B-Cell Differentiation

描述（由申请人提供）：具体来说，这是一个正在进行的项目AI-20069题为“哺乳动物b细胞分化的早期事件”，要求增加第三个特定目标“研究造血的谱系稳定性和方向性”。该实验将严格验证一个新概念，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，干细胞在产生谱系受限的祖细胞之前，通常会在不同的状态之间振荡。同样的现象可以解释恶性肿瘤保留罕见肿瘤干细胞的能力。更好地了解造血细胞的稳定性将有助于了解免疫系统在正常和疾病情况下是如何被取代的。鉴于这一概念的创新性，这些实验可能会开辟一条全新的研究路线。然而，我们需要额外的人员和物资，以及生物信息学和微阵列支持，这些支持可以通过隶属于OMRF的NCRR支持的COBRE获得，该COBRE名为“指导文化中的科学（RR015577）”。这个COBRE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，本补充所涵盖的杰出年轻研究者将受益于与COBRE的互动，并被培养为最终成为独立教员的地位。此外，母公司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均已准备就绪，可在两年内完成研究计划。

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.