The regulative role of DAXX in the gene expression in C9HRE ALS/FTD patient motor neurons

To investigate the role of DAXX in the C9HRE-associated gene dysregulation inALS/FTD patient-derived motor neurons. Two pairs of C9HRE ALS/FTD patient iPSCs and their isogenic controls, in which the C9Orf72 HRE mutation was removed, were differentiated into motor neurons. RNA-seq was employed to profile the global gene expression in the isogenic iMNs, C9HRE iMNs, and the C9HRE iMNs treated with shRNA targeting DAXX.

本研究旨在探究死亡结构域相关蛋白（DAXX）在肌萎缩侧索硬化/额颞叶痴呆（Amyotrophic Lateral Sclerosis/Frontotemporal Dementia, ALS/FTD）患者来源运动神经元中C9HRE相关基因失调中的调控作用。我们选取了两对C9HRE型ALS/FTD患者诱导多能干细胞（induced pluripotent stem cells, iPSCs）及其同基因对照细胞（该对照细胞已剔除C9Orf72 HRE突变），并将两类细胞均诱导分化为运动神经元。随后采用RNA测序（RNA-sequencing, RNA-seq）技术，对三类样本的全基因表达谱进行分析：同基因对照诱导运动神经元（isogenic iMNs）、C9HRE型诱导运动神经元（C9HRE iMNs），以及经靶向DAXX的短发夹RNA（short hairpin RNA, shRNA）处理的C9HRE型诱导运动神经元。