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

描述（由申请人提供）：我们的长期研究目标是了解调节干细胞命运决定的机制。为了确保血液和免疫细胞的终身供应，造血干细胞（HSC）必须通过适当地响应来自环境的复杂和动态输入来平衡自我更新和分化。本提案的目标是开发两种新的小鼠模型，这两种模型将作为分析控制HSC功能的内在和外在机制的重要工具。这些新模型将使我们能够探索调节造血稳态的机制，生态位在造血干细胞命运决定和移植中的作用，辐射诱导效应如何影响这些过程，以及现有方法无法回答的一系列其他问题。该结果将促进HSC体外扩增，并指导提高HSC移植治疗的安全性和有效性的策略。

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. .