In vivo mouse models for inducible hematopoietic- and hematopoietic stem cell-spe

描述(由申请者提供)：我们的长期研究目标是了解调节干细胞命运决定的机制。为了确保终生血液和免疫细胞的供应，造血干细胞(HSC)必须通过对复杂和动态的环境输入做出适当的反应，在自我更新和分化之间取得平衡。这项建议的目标是开发两种新的小鼠模型，作为解剖支配HSC功能的内在和外在机制的重要工具。这些新的模型将使我们能够探索调节造血稳态的机制，在造血干细胞命运决定和植入中的作用，辐射诱导的效应如何影响这些过程，以及一系列其他用现有方法无法回答的问题。这一结果将促进HSC的体外扩增，并指导提高HSC移植治疗的安全性和效率的策略。。

DESCRIPTION (provided by applicant): Our long-term research goals are to understand the mechanisms that regulate stem cell fate decisions. To ensure a life-long supply of blood and immune cells, the hematopoietic stem cell (HSC) must balance self-renewal with differentiation by responding properly to complex and dynamic inputs from the environment. The goal of this proposal is to develop two new mouse models that will serve as important tools for dissecting the intrinsic and extrinsic mechanisms that govern HSC function. These new models will enable us to pursue the mechanisms regulating hematopoietic homeostasis, the role of niches in HSC fate decisions and engraftment, how radiation-induced effects influence these processes, and a range of other questions that cannot be answered by existing methods. The outcomes will facilitate ex vivo HSC expansion and guide strategies for improving the safety and efficiency of HSC transplantation therapies. .