Genomic imprinting is an epigenetic modification of DNA, whereby gene expression is restricted to either maternally or paternally inherited alleles. Imprinted genes (IGs) in the placenta and embryo are essential for growth regulation and nutrient supply. However, despite being an important nutrition delivery organ, studies on mammary gland genomic imprinting remain limited. In this study, we found that both the number of IGs and their expression levels decreased during development of the mouse mammary gland. IG expression was lineage-specific and related to mammary gland development and lactation. Meta-analysis of single-cell RNA sequencing data revealed that mammary gland IGs were co-expressed in a network that regulated cell stemness and differentiation, which was confirmed by our functional studies. Accordingly, our data indicated that IGs were essential for the self-renewal of mammary gland stem cells and IG decline was correlated with mammary gland maturity. Taken together, our findings revealed the importance of IGs in a poorly studied nutrition-related organ, i.e. the mammary gland, thus providing a reference for further studies on genomic imprinting.
