ZFP57 is a regulator of postnatal growth and life-long health

Early-life factors, including nutrition, shape long-term health outcomes. Despite the essential role of lactation in maternal nutritional support, the influence of epigenetic factors on lactation and postnatal growth remains poorly understood. Zinc-finger protein 57 (ZFP57), is an epigenetic regulator of genomic imprinting, a process that directs gene expression based on parental origin, playing a vital role in mammalian prenatal growth. Here, we identify a novel function of ZFP57 in the mammary glandI, where it serves as a key modulator of postnatal resource control, independently of imprinted genes. ZFP57 regulates multiple aspects of mammary gland functions, including ductal branching and cellular homeostasis. Its absence leads to significant differential gene expression, related to alveologenesis, lactogenesis and milk synthesis, associated with delayed lactation and altered milk composition. This results in life-long impacts on offspring including the development of metabolic syndrome. Cross-fostering reveals intricate dynamics between mother and offspring during lactation. Pups raised by a dam of a different genotype than their birth mother exhibit exacerbated metabolic features in adulthood, providing additional novel insight into the programming of offspring long-term health by maternal context. This study deepens our understanding of the interplay between epigenetic factors, lactation, and postnatal resource control. Mammary tissue from Wild type and ZFP57 KO mice were collected at various stages during pregancy and sorted into descreet cell population. RNA from each of these cell types were the harvested and sequenced to profile in impact ZFP57 KO has on transcriptional regulation of mammary cells during pregancy

早期生命因素（包括营养状况）可塑造个体的长期健康结局。尽管泌乳在母体营养支持中发挥核心作用，但表观遗传（epigenetic）因素对泌乳及产后生长的影响仍有待深入阐释。锌指蛋白57（Zinc-finger protein 57, ZFP57）是基因组印记（genomic imprinting）的表观遗传调控因子——基因组印记是一种根据亲本来源调控基因表达的过程，对哺乳动物的产前生长至关重要。本研究首次揭示了ZFP57在乳腺中的全新功能：它可作为产后资源调控的关键调节因子，且不依赖于印记基因。ZFP57可调控乳腺功能的多个方面，包括导管分支与细胞稳态。当ZFP57缺失时，会引发与乳腺腺泡发育、泌乳启动及乳汁合成相关的显著差异基因表达，进而导致泌乳延迟与乳汁成分改变。这会对子代产生终身影响，包括代谢综合征的发生风险升高。交叉寄养实验揭示了泌乳过程中母体与子代间复杂的互作动态。由基因型不同于生母的养母抚育的子代，在成年后会表现出更严重的代谢异常表型，这为阐释母体环境如何程序化调控子代长期健康提供了新的见解。本研究加深了我们对表观遗传因素、泌乳与产后资源调控之间相互作用的认知。本研究收集了野生型（Wild type, WT）与ZFP57基因敲除（ZFP57 KO）小鼠在妊娠不同阶段的乳腺组织，并将其分选为离散的细胞群体。随后提取各细胞群体的RNA进行测序，以解析ZFP57敲除对妊娠期间乳腺细胞转录调控的影响。