A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation [CUT&RUN Chip-seq]

RUNX1 is crucial for multiple stages of hematopoiesis and its mutation can cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). We aim to study the role of RUNX1 in megakaryocyte-biased HSCs differentiation to megakaryocytes. Here, by using Runx1F/FMx1-Cre mouse model ,we sorted CD41pos HSCs and CD41neg HSCs in both RUNX1 WT and KO, and tested the RUNX1 direct binding targets in these cells genome. Overall design: Comparative RUNX1 binding target genes acquired from CUT&RUN for RUNX1and H3K4me3 in CD41pos HSCs and CD41neg HSCs from both RUNX1 KO and WT mice.

RUNX1（runt相关转录因子1）在造血过程的多个阶段发挥关键调控作用，其突变可引发伴急性髓系白血病易感倾向的家族性血小板障碍（FPD/AML）。本研究旨在探究RUNX1在偏向巨核细胞的造血干细胞向巨核细胞分化过程中的功能。本研究借助Runx1F/FMx1-Cre小鼠模型，分别从RUNX1野生型（Wild Type, WT）与敲除型（Knockout, KO）小鼠中分选CD41阳性造血干细胞（CD41pos HSCs）与CD41阴性造血干细胞（CD41neg HSCs），并对这些细胞基因组中的RUNX1直接结合靶点进行检测。整体实验设计：分别对RUNX1野生型与敲除型小鼠的CD41pos HSCs及CD41neg HSCs开展RUNX1与H3K4me3的CUT&RUN实验，以获取二者的结合靶基因并进行比较分析。