Sex specific gene expression differences in mouse pups from obese dams

Maternal obesity is increasingly common and negatively impact offspring health. Children born to mothers with obesity are at higher risk of developing diseases associated with abnormalities within the hematopoietic system such as atypical immune profiles, hematopoiesis, and metabolic diseases such as type 2 diabetes. Interestingly, disease risks are often dependent on the offspring’s sex, suggesting sex-specific reprogramming effect of maternal obesity on offspring hematopoietic stem and progenitor cell (HSPC) function. However, the impact of maternal obesity exposure on offspring HSPC function is largely unknown, and the capability of HSPC to regulate offspring metabolic health has not been studied. Here we examined differential transcriptomes of hematopoietic stem and progenitor cells from male and female pups (postnatal day 21) from dams given western diet or control diet. RNA-seq revealed inflammatory gene pathways in female MatOb offspring that potentially protect HSPC function. Bone marrow was harvested from male and female postnatal day 21 pups born to mothers that were fed a western diet or control diet. Lineage negative, Sca positive, Kit positive (LSK) cells were isolated using florescence activated cell sorting (FACS) and RNA was harvested for sequencing.

母体肥胖（maternal obesity）愈发普遍，且对子代健康存在负面影响。母体肥胖母鼠所分娩的子代，罹患造血系统异常相关疾病（如非典型免疫谱异常、造血功能紊乱）及代谢性疾病（如2型糖尿病）的风险更高。值得注意的是，疾病风险往往随子代性别而异，提示母体肥胖对子代造血干细胞与祖细胞（hematopoietic stem and progenitor cell, HSPC）功能存在性别特异性重编程效应。然而，母体肥胖暴露对子代HSPC功能的影响目前尚不明晰，且HSPC调控子代代谢健康的能力尚未得到研究。本研究对饲喂西式饮食或对照饮食的母鼠所产下的产后第21天（P21）雌雄仔鼠的造血干细胞与祖细胞的差异转录组进行了分析。RNA测序（RNA-seq）结果显示，母体肥胖雌性子代的炎症基因通路或可对HSPC功能起到保护作用。本研究从饲喂西式饮食或对照饮食的母鼠所产下的产后第21天（P21）雌雄仔鼠体内采集骨髓样本，采用荧光激活细胞分选术（fluorescence activated cell sorting, FACS）分离得到谱系阴性、Sca-1阳性、c-Kit阳性（LSK）细胞，并提取RNA用于测序。