Affiliations: 1) Institute of Biochemistry, ETH Zurich, Zurich, Switzerland; 2) Department of Biology, ETH Zurich, Zurich, Switzerland; 3) Life Science Zurich Graduate School, Zurich, Switzerland
Keywords: k. nuclear organization; b. germline stem cell
The balance between stem cell self-renewal and differentiation is essential to maintain tissue homeostasis. Previous studies have highlighted that the heterochromatin-associated protein, Stonewall (Stwl), is important for the maintenance of germline stem cells (GSC) in the Drosophila ovary; Stwl loss-of-function results in agametic ovaries while its overexpression results in an increase of undifferentiated cells. However, the mechanism by which Stwl maintains the GSC fate in the female germline remains incompletely understood. We hypothesized that Stwl regulates the balance between self-renewal and differentiation by modulating gene expression in GSCs. To test this, we measured gene expression changes upon overexpression of Stwl in a GSC-enriched population. Our data showed that Stwl overexpression was associated with the downregulation of genes encoding components of extracellular matrix, germline-enriched ribosomal genes as well as germline-associated cytoskeletal genes. Strikingly, we also observe that germline-specific knockdown of Stwl is associated with a specific loss of nuclear lamina in GSCs. Interestingly, tethering genomic loci to the repressive environment of the nuclear lamina has been shown to regulate cell-type-specific gene expression. As such, loss of the nuclear lamina may allow improper gene expression in Stwl-depleted GSCs, leading to their loss. Together, we propose that Stwl tethers differentiation genes to the nuclear lamina in GSCs and orchestrates a gene expression program that promotes self-renewal.