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 growt...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 sternness 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.展开更多
基金This work was supported by the National Key Research and Development Program of China(2016YFA0100900)the National Natural Science Foundation of China(U1802285,31970612,81871403,and 81571738)+3 种基金Yunnan Applied Basic Research Key Projects(2018FA002 and 2015HA026)Key Research and Development Program of Zhejiang Province(2019C03014)Open Project from the State Key Laboratory of Genetic Resources and Evolution(GREKF20-0A)Fundamental Research Funds for the Central Universities.
文摘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 sternness 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.