TWIST1 is required for HSC maintenance under steady state and stress condition by inhibiting mitochondrial metabolism gene program. TWIST1 is required for HSC maintenance under steady state and stress condition by inhibiting mitochondrial metabolism gene program

RNA-seq and ATAC-seq were performed to determine possible downstream molecular mechamisms and the changes in chromatin accessibility in long-term hematopoietic stem cell when TWIST1 was absent following irradiation stress. We found that mitochondrial metabolism pathway was strongly turned on in the Twist1-deficient LT-HSCs upon irradiation stress. Overall design: a) RNA-seq in Twist1-deleted and control LT-HSCs following irradiation treatment; b) ATAC-seq in Twist1-deleted and control LT-HSCs following irradiation treatment; c) RNA-seq in Twist1-deleted and control LT-HSCs under steady state.

本研究通过RNA测序（RNA-seq）与转座酶可及性测序（ATAC-seq），旨在探究辐射应激条件下TWIST1缺失时，长期造血干细胞（long-term hematopoietic stem cell, LT-HSCs）内潜在的下游分子机制以及染色质可及性的变化。我们发现，辐射应激下Twist1缺陷型长期造血干细胞的线粒体代谢通路被显著激活。整体实验设计如下：
a) 辐射处理后的Twist1敲除与对照组长期造血干细胞的RNA测序；
b) 辐射处理后的Twist1敲除与对照组长期造血干细胞的转座酶可及性测序；
c) 稳态条件下Twist1敲除与对照组长期造血干细胞的RNA测序。