Transcriptomic profiling of E9.5 mouse embryos lacking the lipoprotein receptor SR-B1

The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, including cholesterol and vitamin E. During early development, SR-B1 is located in the maternal-fetal interface, where it facilitates vitamin E transport towards the embryo. Consequently, embryos lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the neural tube and show neural tube defects (NTD). Here, we studied the transcriptomic profile of mouse embryos lacking SR-B1 to identify the molecular determinants of this phenotypic difference. We used RNA-Seq to analyze the expression of mRNA globally in E9.5 wild-type embryos and embryos lacking SR-B1 with or without NTD, in order to compare expression profiles in those groups and to identify putative genes driving phenotypic differences. Overall design: We analyzed 3 samples of each group (wild-type, SR-B1 KO normal, SR-B1 KO NTD). Each samples corresponded to a pool of 3 embryos.高密度脂蛋白受体SR-B1（high-density lipoprotein receptor SR-B1）可介导细胞摄取包括胆固醇、维生素E在内的多种脂质。在胚胎发育早期，SR-B1定位于母胎界面，可促进维生素E向胚胎的转运。因此，缺失SR-B1的胚胎会出现维生素E缺乏症，其中约半数无法完成神经管闭合，进而表现出神经管缺陷（NTD）。本研究针对缺失SR-B1的小鼠胚胎开展转录组谱分析，以阐明该表型差异的分子决定因素。我们采用RNA测序（RNA-Seq）技术，对发育第9.5天（E9.5）的野生型胚胎、缺失SR-B1且伴或不伴神经管缺陷的胚胎进行全信使RNA（mRNA）的全局表达分析，通过比较各组间的表达谱差异，筛选出可能驱动表型差异的候选基因。实验设计概况：本研究对每组（野生型组、SR-B1基因敲除正常表型组、SR-B1基因敲除神经管缺陷组）各取3份样本进行分析，每份样本均由3枚胚胎混合制备而成。