PDF(Pubmed)
Abstract：
UNASSIGNED: Maternal obesity is a health concern that may predispose newborns to a high risk of medical problems later in life. To understand the transgenerational effect of maternal obesity, we conducted a multi-omics study, using DNA methylation and gene expression in the CD34+/CD38-/Lin- umbilical cord blood hematopoietic stem cells (uHSCs) and metabolomics of the cord blood, all from a multi-ethnic cohort (n=72) from Kapiolani Medical Center for Women and Children in Honolulu, Hawaii (collected between 2016 and 2018).
UNASSIGNED: Differential methylation (DM) analysis unveiled a global hypermethylation pattern in the maternal pre-pregnancy obese group (BH adjusted p<0.05), after adjusting for major clinical confounders. Comprehensive functional analysis showed hypermethylation in promoters of genes involved in cell cycle, protein synthesis, immune signaling, and lipid metabolism. Utilizing Shannon entropy on uHSCs methylation, we discerned notably higher quiescence of uHSCs impacted by maternal obesity. Additionally, the integration of multi-omics data-including methylation, gene expression, and metabolomics-provided further evidence of dysfunctions in adipogenesis, erythropoietin production, cell differentiation, and DNA repair, aligning with the findings at the epigenetic level. Furthermore, the CpG sites associated with maternal obesity from these pathways also predicted highly accurately (average AUC = 0.8687) between cancer vs. normal tissues in 14 cancer types in The Cancer Genome Atlas (TCGA).
UNASSIGNED: This study revealed the significant correlation between pre-pregnancy maternal obesity and multi-omics level molecular changes in the uHSCs of offspring, particularly in DNA methylation. Moreover, these maternal obesity epigenetic markers in uHSCs may predispose offspring to higher cancer risks.
UNASSIGNED: Differential methylation (DM) analysis unveiled a global hypermethylation pattern in the maternal pre-pregnancy obese group (BH adjusted p<0.05), after adjusting for major clinical confounders. Comprehensive functional analysis showed hypermethylation in promoters of genes involved in cell cycle, protein synthesis, immune signaling, and lipid metabolism. Utilizing Shannon entropy on uHSCs methylation, we discerned notably higher quiescence of uHSCs impacted by maternal obesity. Additionally, the integration of multi-omics data-including methylation, gene expression, and metabolomics-provided further evidence of dysfunctions in adipogenesis, erythropoietin production, cell differentiation, and DNA repair, aligning with the findings at the epigenetic level. Furthermore, the CpG sites associated with maternal obesity from these pathways also predicted highly accurately (average AUC = 0.8687) between cancer vs. normal tissues in 14 cancer types in The Cancer Genome Atlas (TCGA).
UNASSIGNED: This study revealed the significant correlation between pre-pregnancy maternal obesity and multi-omics level molecular changes in the uHSCs of offspring, particularly in DNA methylation. Moreover, these maternal obesity epigenetic markers in uHSCs may predispose offspring to higher cancer risks.
摘要：
母亲肥胖是一个健康问题，可能会使新生儿在以后的生活中出现医疗问题的风险很高。了解母亲肥胖的跨代效应,我们进行了一项多组学研究，使用DNA甲基化和基因表达在CD34+/CD38-/Lin-脐带血造血干细胞（uHSCs）和代谢组学的脐带血，全部来自檀香山Kapiolani妇女和儿童医学中心的多种族队列（n=72），夏威夷（2016年至2018年收集）。
■差异甲基化（DM）分析揭示了孕妇孕前肥胖组的整体超甲基化模式（BH调整p<0.05），在调整了主要临床混杂因素后。综合功能分析显示细胞周期相关基因的启动子高度甲基化,蛋白质合成，免疫信号，和脂质代谢。利用Shannon熵对uHSCs甲基化，我们发现受母亲肥胖影响的uHSC的静止期明显较高。此外,多组学数据的整合-包括甲基化，基因表达，代谢组学提供了脂肪生成功能障碍的进一步证据，促红细胞生成素的生产，细胞分化，和DNA修复,与表观遗传水平的发现一致。
■这项研究揭示了孕前母亲肥胖与子代uHSCs的多组学水平分子变化之间的显着相关性，特别是在DNA甲基化中。
■差异甲基化（DM）分析揭示了孕妇孕前肥胖组的整体超甲基化模式（BH调整p<0.05），在调整了主要临床混杂因素后。综合功能分析显示细胞周期相关基因的启动子高度甲基化,蛋白质合成，免疫信号，和脂质代谢。利用Shannon熵对uHSCs甲基化，我们发现受母亲肥胖影响的uHSC的静止期明显较高。此外,多组学数据的整合-包括甲基化，基因表达，代谢组学提供了脂肪生成功能障碍的进一步证据，促红细胞生成素的生产，细胞分化，和DNA修复,与表观遗传水平的发现一致。
■这项研究揭示了孕前母亲肥胖与子代uHSCs的多组学水平分子变化之间的显着相关性，特别是在DNA甲基化中。
