Functional Analysis Of Transcription Factor STAT3 In Mouse Female Germline Stem Cells

For decades,a widely accepted view in reproductive biology is that the production of oocytes in female mammals has ceased before birth due to the inexistence of germline stem cells,which is different from male mammals.However,such view has been challenged by an increasing number of recent studies in which mammalian germline stem cells have been isolated from the ovaries of mouse,pig and human.Although mouse female germline stem cells(mFGSCs)are unipotent stem cell that can both sustain self-renewal and give rise to oocyte,the detailed molecular regulation mechanisms and basic biological characteristics of FGSCs are unclear.LIF-mediated JAK-STAT3 signaling is critically involved in stem cells and development.However,its function in mouse female germline cells(mFGSCs)remains elusive.In this study,we demonstrated that LIF-induced STAT3 activation contributes to the proliferation and undifferentiation maintenance of mouse FGSCs.Using RNA-seq analysis of differentially expressed genes between wild type and Stat3 knockout FGSCs and ChIP-seq identification of genome-wide STAT3 binding sites in wild type FGSCs,we revealed 405 STAT3 direct target genes,which are primarily involved in proliferation and germline development.In particular,we observed STAT3 exhibits FGSC-specific binding pattern when compared with mouse embryonic stem cells(mESCs)STAT3 ChIP-seq data.Taken together,our study reported the LIF-mediated STAT3 activation is actively involved in FGSCs and functions through a distinctive binding pattern across FGSC genome.Moreover,our work provides resources for further analysis of self-renewal,differentiation and clinical application of FGSCs.