Expression changes in mouse oligodendrocytes after deletion of the Ep400 chromatin remodeler

To address the role of INO80/SWR-type remodeling complexes, we deleted Ep400 at defined times of mouse oligodendrocyte development. Whereas oligodendrocyte precursors are specified and develop normally without Ep400, terminal differentiation is dramatically impaired resulting in hypomyelination. RNA-Seq studies were performed on cultured and FACS sorted control and Ep400-deficient mouse oligodendrocytes to analyze changes in gene expression. These revealed that genes associated with the myelination program and with response to DNA damage are altered in Ep400-deficient oligodendrocytes. OPC mRNA profiles of 6-day old control (ctrl) and Ep400 cko mice were generated using the Illumina HiSeq 2500 platform.为探究INO80/SWR型染色质重塑复合物的功能，我们在小鼠少突胶质细胞发育的特定时间节点敲除了Ep400基因。尽管缺失Ep400的少突胶质细胞前体细胞（oligodendrocyte precursors）可正常特化与发育，但其终末分化过程会受到显著损伤，进而导致低髓鞘形成。为分析基因表达变化，我们对体外培养且经荧光激活细胞分选（FACS，fluorescence-activated cell sorting）分离的野生型与Ep400缺陷型小鼠少突胶质细胞开展了RNA测序（RNA-Seq）实验。测序结果显示，在Ep400缺陷型少突胶质细胞中，与髓鞘形成程序及DNA损伤应答相关的基因表达发生了改变。本研究使用Illumina HiSeq 2500测序平台，获取了6日龄野生型（ctrl，control）与Ep400条件性敲除（cko，conditional knockout）小鼠的少突胶质细胞前体细胞（OPC，oligodendrocyte precursor cells）mRNA表达谱。