SummaryAdult and embryonic stem cells exhibit fluctuating gene expression; however, the biological significance of stem cell heterogeneity is not well understood. We show that, in Drosophila, female germline stem cells (GSCs) exhibit heterogeneous expression of a GSC differentiation-promoting factor Regena (Rga). The Drosophila homolog of human SON, dsn, is required to maintain GSC heterogeneity by suppressing sustained high levels of Rga. Reducing the expression of Rga in dsn mutants restores GSC heterogeneity and self-renewal. Thus, GSC heterogeneity is linked to GSC homeostasis.