Project 2 - Cell of origin contributions and vulnerabilities in clonal hematopoiesis

项目摘要 造血干细胞(HSC)隔室内的异质性是被很好地定义的，我们 假设可能有助于从克隆的启动中出现广泛的表型 造血(CH)。该项目将使用独特的工具来评估上下文中的单元状态 以确定起源细胞的表观遗传和转录程序 影响克隆显性。这些数据将为深入了解克隆的机制提供帮助。 显性，并可能提供表观遗传签名，表明风险，以供后续验证。我们 还将重点研究优势CH的代谢状态，以确定这些细胞的特征 使他们容易受到低强度的干预。成功的成就将指导 选择性耗尽异常显性无性系的策略。

Project Summary Heterogeneity within the hematopoietic stem cell (HSC) compartment is well defined and we hypothesize may contribute to the wide range of phenotypes emerging from initiation of clonal hematopoiesis (CH). This project will use distinctive tools for assessing cell state in the context of Tet2 deletion to determine how the epigenetic and transcriptional program of the cell of origin affects clonal dominance. These data will provide insight into the mechanisms of clonal dominance and may offer epigenetic signatures indicative of risk for subsequent validation. We will also focus on the metabolic state of dominant CH to define whether features of those cells render them vulnerable to low intensity intervention. Successful accomplishment will guide strategies for selective depletion of aberrant dominant clones.