RNA-seq of murine proliferating neural stem and progenitor cells from Kat7-deleted mouse fetuses

Tissue-specific deletion of the gene encoding the histone acetyltransferase Kat7 (Hbo1) in the developing mouse central nervous system using cre-recombinase expression driven by regulatory sequences of the nestin locus (NesCre transgene) resulted in defective cerebral cortex development, a complete failure of neural stem cells to give rise to neurons and oligodendrocytes during in vitro differentiation, and a failure to express the neuronal differentiation program. Proliferating neural stem and progenitor cells (NPSCs) were isolated from Kat7-deleted and Kat7-intact 14.5 day embryonic mouse fetuses. Overall design: RNA-seq profiling was undertaken of NSPC isolates from four Kat7-deleted (Kat7lox/loxNesCreT/+) and four Kat7-intact (Kat7+/+NesCreT/+) E14.5 fetuses. For completeness, the litter number that each embryo was obtained from was also recorded.

本研究借助由巢蛋白基因座（nestin locus）调控序列驱动的Cre重组酶（cre-recombinase）表达系统，在发育中小鼠中枢神经系统中对编码组蛋白乙酰转移酶Kat7（Hbo1）的基因开展组织特异性敲除，实验结果显示：该操作引发大脑皮层发育缺陷，神经干细胞在体外分化过程中完全无法生成神经元与少突胶质细胞，且无法启动神经元分化程序。研究人员从Kat7敲除型与Kat7未敲除型的14.5天胚胎小鼠胎体中分离得到增殖态神经干细胞及祖细胞（neural stem and progenitor cells, NPSCs）。实验设计概述：对4只Kat7敲除型（Kat7lox/loxNesCreT/+）及4只Kat7未敲除型（Kat7+/+NesCreT/+）的E14.5胎鼠的NPSCs分离物进行RNA测序（RNA-seq）转录组谱分析；为保证数据完整性，同时记录了每枚胚胎所属的同窝胎仔编号。