Germline stem cell (GSC) self-renewal and differentiation are required for the sustained production of gametes. GSC differentiation in Drosophila oogenesis requires expression of the histone methyltransferase dSETDB1 by the somatic niche, however its function in this process is unknown. Here, we show that dSETDB1 is required for the expression of a Wnt ligand, Drosophila W ingless type mouse mammary virus i nt egration site number 4 (dWnt4) in the somatic niche. dWnt4 signaling acts on the somatic niche cells to facilitate their encapsulation of the GSC daughter, which serves as a differentiation cue. dSETDB1 is known to repress transposable elements (TEs) to maintain genome integrity. Unexpectedly, we found that independent upregulation of TEs also downregulated dWnt4 , leading to GSC differentiation defects. This suggests that dWnt4 expression is sensitive to the presence of TEs. Together our results reveal a chromatin-transposon-Wnt signaling axis that regulates stem cell fate. Author Summary Every multicellular organism is made up of tissues that are maintained by stem cells, due to their capacity to both self-renew and differentiate into terminal cell types. Loss of either of these processes can lead to aging, progression towards degenerative diseases and cancers. Insight into how self-renewal and differentiation are regulated will have tremendous therapeutic impact. Drosophila is an excellent model system for stem cell study due to the availability of various mutants, markers and RNAi technology. We study the ovaries of the female Drosophila , whose stem cell population gives rise to gametes. The tissue from which these gametes arise is surrounded by somatic cells, which provide signaling cues required for proper self-renewal and differentiation. While the mechanisms by which these somatic signals regulate stem cell self-renewal is known, how somatic cues regulate differentiation remains unclear. Here, we have identified that transposons, selfish genetic elements, modulate dWnt4 expression in the somatic cells. We demonstrate that dWnt4 promotes the somatic encapsulation of the stem cell daughter by regulating adherens junction proteins, thereby promoting differentiation. Transposons have been linked to cancers, and therefore establishing how transposons regulate genes essential for differentiation can provide new perspectives on their role in cancer.
【초록키워드】 stem cells, aging, Cancer, Genome, Genetic, Proteins, progression, virus, cancers, methyltransferase, therapeutic, female, mutants, encapsulation, differentiation, disease, expression, mechanism, marker, Signaling, Ligand, regulate, stem cell, lead, multicellular organism, cell types, transposable elements, somatic cells, degenerative diseases, differentiation defects, elements, Drosophila, tissue, tissues, Perspective, germline, upregulation, organism, acts, chromatin, oogenesis, transposons, Wnt4, element, cell fate, while, cell population, Loss, insight, Cell, independent, Wnt, required, facilitate, modulate, promote, maintain, regulated, sustained, downregulated, transposon, repress, degenerative, multicellular, GSC, mammary, 【제목키워드】 Control, stem cell, germline, STEM,