RESUMEN
The Drosophila intestine is maintained by multipotent intestinal stem cells (ISCs). Although increased intestinal stem cell (ISC) proliferation has been correlated with a decrease in longevity, there is some discrepancy regarding whether a decrease or block in proliferation also has negative consequences. Here we identify headcase (hdc) as a novel marker of ISCs and enteroblasts (EBs) and demonstrate that Hdc function is required to prevent ISC/EB loss through apoptosis. Hdc depletion was used as a strategy to ablate ISCs and EBs in order to test the ability of flies to survive without ISC function. While flies lacking ISCs showed no major decrease in survival under unchallenged conditions, flies depleted of ISCs and EBs exhibited decreased survival rates in response to damage to mature enterocytes (EC) that line the intestinal lumen. Our findings indicate that constant renewal of the intestinal epithelium is not absolutely necessary under normal laboratory conditions, but it is important in the context of widespread chemical-induced damage when significant repair is necessary.
Asunto(s)
Drosophila melanogaster/citología , Intestinos/citología , Células Madre/citología , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Bleomicina/toxicidad , Supervivencia Celular/efectos de los fármacos , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/efectos de los fármacos , Femenino , Regeneración/efectos de los fármacos , Células Madre/efectos de los fármacos , Células Madre/metabolismoRESUMEN
Stem cells reside within specialized microenvironments, or niches, that control many aspects of stem cell behavior. Somatic hub cells in the Drosophila testis regulate the behavior of cyst stem cells (CySCs) and germline stem cells (GSCs) and are a primary component of the testis stem cell niche. The shutoff (shof) mutation, characterized by premature loss of GSCs and CySCs, was mapped to a locus encoding the evolutionarily conserved transcription factor Escargot (Esg). Hub cells depleted of Esg acquire CySC characteristics and differentiate as cyst cells, resulting in complete loss of hub cells and eventually CySCs and GSCs, similar to the shof mutant phenotype. We identified Esg-interacting proteins and demonstrate an interaction between Esg and the corepressor C-terminal binding protein (CtBP), which was also required for maintenance of hub cell fate. Our results indicate that niche cells can acquire stem cell properties upon removal of a single transcription factor in vivo.
Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Nicho de Células Madre , Células Madre/citología , Testículo/citología , Alelos , Animales , Linaje de la Célula , Proteínas de Drosophila/genética , Células Germinativas/citología , Células Germinativas/metabolismo , Masculino , Células Madre/metabolismo , Factores de Transcripción/metabolismoRESUMEN
At the apical tip of the Drosophila testis, germline and somatic stem cells surround a cluster of somatic cells called the hub. Hub cells produce a self-renewal factor, Unpaired (Upd), that activates the JAK-STAT pathway in adjacent stem cells to regulate stem cell behavior. Therefore, apical hub cells are a critical component of the stem cell niche in the testis. In the course of a screen to identify factors involved in regulating hub maintenance, we identified headcase (hdc). Hub cells depleted for hdc undergo programmed cell death, suggesting that anti-apoptotic pathways play an important role in maintenance of the niche. Using hdc as paradigm, we describe here the first comprehensive analysis on the effects of a progressive niche reduction on the testis stem cell pool. Surprisingly, single hub cells remain capable of supporting numerous stem cells, indicating that although the size and number of niche support cells influence stem cell maintenance, the testis stem cell niche appears to be remarkably robust in the its ability to support stem cells after severe damage.
Asunto(s)
Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila/genética , Drosophila/metabolismo , Nicho de Células Madre/fisiología , Testículo/metabolismo , Animales , Apoptosis/genética , Supervivencia Celular/genética , Masculino , Interferencia de ARN , Células Madre/metabolismo , TranscriptomaRESUMEN
Tissue stem cells are found in specialized microenvironments (niches) where they are exposed to diverse systemic and local signals that are integrated with cell intrinsic factors to regulate stem cell behavior. In general, systemic signals are utilized to coordinate the response of tissues to acute or long-term changes that affect the whole organism, such as variations in nutrient availability or aging. In contrast, local signaling regulates tissue maintenance by balancing stem cell self-renewal with differentiation under homeostatic conditions and in response to local damage. In this review, we highlight the role of the JAK-STAT pathway in two Drosophila stem cell systems, the testis and intestine, and compare and contrast how activation of this pathway leads to tissue maintenance under both homeostatic conditions and in response to stress or injury.