RESUMO
Adults maintain tissue-specific stem cells through niche signals. A model for niche function is the Drosophila melanogaster testis, where a small cluster of cells called the hub produce locally available signals that allow only adjacent cells to self-renew. We show here that the principal signalling pathway implicated in this niche, chemokine activation of STAT, does not primarily regulate self-renewal of germline stem cells (GSCs), but rather governs GSC adhesion to hub cells. In fact, GSC renewal does not require hub cell contact, as GSCs can be renewed solely by contact with the second resident stem cell population, somatic cyst stem cells (CySCs), and this involves BMP signalling. These data suggest a modified paradigm whereby the hub cells function as architects of the stem cell environment, drawing into proximity cellular components necessary for niche function. Self-renewal functions are shared by the hub cells and the CySCs. This work also reconciles key differences in GSC renewal between Drosophila testis and ovary niches, and highlights how a niche can coordinate the production of distinct lineages by having one stem cell type rely on a second.
Assuntos
Nicho de Células-Tronco/fisiologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Testículo/metabolismo , Animais , Drosophila , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Células Germinativas/citologia , Células Germinativas/fisiologia , Masculino , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
The ability of adult stem cells to maintain their undifferentiated state depends upon residence in their niche. While simple models of a single self-renewal signal are attractive, niche-stem cell interactions are likely to be more complex. Many niches have multiple cell types, and the Drosophila testis is one such complex niche with two stem cell types, germline stem cells (GSCs) and somatic cyst progenitor cells (CPCs). These stem cells require chemokine activation of Jak/STAT signaling for self-renewal. We identified the transcriptional repressor Zfh-1 as a presumptive somatic target of Jak/STAT signaling, demonstrating that it is necessary and sufficient to maintain CPCs. Surprisingly, sustained zfh-1 expression or intrinsic STAT activation in somatic cells caused neighboring germ cells to self-renew outside their niche. In contrast, germline-intrinsic STAT activation was insufficient for GSC renewal. These data reveal unexpected complexity in cell interactions in the niche, implicating CPCs in GSC self-renewal.
Assuntos
Proteínas de Ligação a DNA/fisiologia , Proteínas de Drosophila/fisiologia , Drosophila/fisiologia , Proteínas Repressoras/fisiologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Testículo/fisiologia , Animais , Divisão Celular , Células Clonais/citologia , Células Clonais/fisiologia , Células Germinativas/citologia , Células Germinativas/fisiologia , Homeostase , Masculino , Dedos de Zinco/fisiologiaRESUMO
The germ lineage has been studied for a long time because of its crucial role in the propagation and survival of a species. While this lineage, in contrast to the soma, is clearly unique in its totipotent ability to produce a new organism, it has now been found also to have specific features at the cellular level. One feature, a period of transcriptional quiescence in the early germ cell precursors, has been observed in both Drosophila and C. elegans, where it is essential for the formation and the survival of the germline. In addition, there are numerous instances where these early germ cells are reliant on translational regulation, especially in Drosophila. The genes that are important for these two functions, the mechanisms of their action, and studies in vertebrate organisms that reveal similarities as well as some potential differences in early germ cell development are discussed.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Inativação Gênica , Células Germinativas/fisiologia , Biossíntese de Proteínas , Transcrição Gênica , Animais , Caenorhabditis elegans/fisiologia , Drosophila melanogaster/fisiologia , Mitocôndrias/genética , RNA Ribossômico/metabolismoRESUMO
Previously, it has been shown that, during early Drosophila and C. elegans development, the germ cell precursors undergo a period of transcriptional quiescence. Here, we report that Germ cell-less (GCL), a germ plasm component necessary for the proper formation of "pole cells," the germ cell precursors in Drosophila, is required for the establishment of this transcriptional quiescence. While control embryos silence transcription prior to pole cell formation in the pole cell-destined nuclei, this silencing does not occur in embryos that lack GCL activity. The failure to establish quiescence is tightly correlated with failure to form the pole cells. Furthermore, we show that GCL can repress transcription of at least a subset of genes in an ectopic context, independent of other germ plasm components. Our results place GCL as the earliest gene known to act in the transcriptional repression of the germline. GCL's subcellular distribution on the nucleoplasmic surface of the nuclear envelope and its effect on transcription suggest that it may act to repress transcription in a manner similar to that proposed for transcriptional silencing of telomeric regions.