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Stem cells have the potential to maintain undifferentiated state and differentiate into specialized cell types. Despite numerous progress has been achieved in understanding stem cell self-renewal and differentiation, many fundamental questions remain unanswered. In this study, we identify dRTEL1, the Drosophila homolog of Regulator of Telomere Elongation Helicase 1, as a novel regulator of male germline stem cells (GSCs). Our genome-wide transcriptome analysis and ChIP-Seq results suggest that dRTEL1 affects a set of candidate genes required for GSC maintenance, likely independent of its role in DNA repair. Furthermore, dRTEL1 prevents DNA damage-induced checkpoint activation in GSCs. Finally, dRTEL1 functions to sustain Stat92E protein levels, the key player in GSC maintenance. Together, our findings reveal an intrinsic role of the DNA helicase dRTEL1 in maintaining male GSC and provide insight into the function of dRTEL1. Author summary: Adult tissue homeostasis is maintained by its resident tissue-specific stem cells. The maintenance of stem cells depends on niche activity (the so-called tissue-specific microenvironment) as well as stem cell intrinsic factors. In a genetic screen, we identify dTREL1 as an intrinsic factor required for the maintenance of Drosophila male germline stem cells (GSCs). Loss of dRTEL1 activity leads to premature loss of male GSCs. Our study shows that dRTEL1 likely functions through multiple downstream genes to promote GSC maintenance. Further results indicate that dRTEL1 also prevents activation of the DNA damage response pathway in GSCs for its maintenance. These factors likely converge on the regulation of Stat92E, a well-studied intrinsic factor for GSC maintenance. [ABSTRACT FROM AUTHOR]

During tumorigenesis, tumor cells interact intimately with their surrounding cells (microenvironment) for their growth and progression. However, the roles of tumor microenvironment in tumor development and progression are not fully understood. Here, using an established benign tumor model in adult Drosophila intestines, we find that n on-cell a utonomous a utophagy (NAA) is induced in tumor surrounding neighbor cells. Tumor growth can be significantly suppressed by genetic ablation of autophagy induction in tumor neighboring cells, indicating that tumor neighboring cells act as tumor microenvironment to promote tumor growth. Autophagy in tumor neighboring cells is induced downstream of elevated ROS and activated JNK signaling in tumor cells. Interestingly, we find that active transport of nutrients, such as amino acids, from tumor neighboring cells sustains tumor growth, and increasing nutrient availability could significantly restore tumor growth. Together, these data demonstrate that tumor cells take advantage of their surrounding normal neighbor cells as nutrient sources through NAA to meet their high metabolic demand for growth and progression. Thus we provide insights into our understanding of the mechanisms underlying the interaction between tumor cells and their microenvironment in tumor development. [Display omitted] • Non-cell autonomous autophagy is induced in tumor surrounding cells in intestines. • Autophagy activation in tumor neighboring cells promotes tumor growth. • Neoplastic Raf gof tumor cells are stressed and produce ROS to ultimately activate autophagy in tumor surrounding cells. • Tumor neighboring cells provide nutrients to sustain tumor growth. [ABSTRACT FROM AUTHOR]

Epithelial polarity is critical for proper functions of epithelial tissues, tumorigenesis, and metastasis. The evolutionarily conserved transmembrane protein Crumbs (Crb) is a key regulator of epithelial polarity. Both Crb protein and its transcripts are apically localized in epithelial cells. However, it remains not fully understood how they are targeted to the apical domain. Here, using Drosophila ovarian follicular epithelia as a model, we show that epithelial polarity is lost and Crb protein is absent in the apical domain in follicular cells (FCs) in the absence of Diamond (Dind). Interestingly, Dind is found to associate with different components of the dynactin‐dynein complex through co‐IP‐MS analysis. Dind stabilizes dynactin and depletion of dynactin results in almost identical defects as those observed in dind‐defective FCs. Finally, both Dind and dynactin are also required for the apical localization of crb transcripts in FCs. Thus our data illustrate that Dind functions through dynactin/dynein‐mediated transport of both Crb protein and its transcripts to the apical domain to control epithelial apico‐basal (A/B) polarity. [ABSTRACT FROM AUTHOR]

Tissue homeostasis is controlled by the differentiated progeny of residential progenitors (stem cells). Adult stem cells constantly adjust their proliferation/differentiation rates to respond to tissue damage and stresses. However, how differentiated cells maintain tissue homeostasis remains unclear. Here, we find that heparan sulfate (HS), a class of glycosaminoglycan (GAG) chains, protects differentiated cells from loss to maintain intestinal homeostasis. HS depletion in enterocytes (ECs) leads to intestinal homeostasis disruption, with accumulation of intestinal stem cell (ISC)‐like cells and mis‐differentiated progeny. HS‐deficient ECs are prone to cell death/stress and induced cytokine and epidermal growth factor (EGF) expression, which, in turn, promote ISC proliferation and differentiation. Interestingly, HS depletion in ECs results in the inactivation of decapentaplegic (Dpp) signaling. Moreover, ectopic Dpp signaling completely rescued the defects caused by HS depletion. Together, our data demonstrate that HS is required for Dpp signal activation in ECs, thereby protecting ECs from ablation to maintain midgut homeostasis. Our data shed light into the regulatory mechanisms of how differentiated cells contribute to tissue homeostasis maintenance. [ABSTRACT FROM AUTHOR]

Stem cells maintain adult tissue homeostasis under physiological conditions. Uncontrolled stem cell proliferation will lead to tumorigenesis. How stem cell proliferation is precisely controlled is still not fully understood. Phosphorylation of Yun is essential for ISC proliferation. Yun is essential for the proliferation of normal and transformed intestinal stem cells. Our mass spectrometry and biochemical data suggest that Yun can be phosphorylated at multiple residues in vivo. Interestingly, we show that the phosphorylation among these residues is likely interdependent. Furthermore, phosphorylation of each residue in Yun is important for its function in ISC proliferation regulation. Thus, our study unveils the important role of post‐translational modification of Yun in stem cell proliferation. [ABSTRACT FROM AUTHOR]

Most, if not all, stem cells reside in a defined microenvironment, called the niche. Short-ranged niche signal must be tightly controlled to be active only inside the niche to maintain the proper balance of stem cell self-renewal verse differentiation. However, how niche components restrict localized niche signal activation remains largely unknown. Here, we find that Thickveins (Tkv, a type I receptor of the Dpp signaling pathway) in cyst stem cells (CySCs) of the testis niche prevents Dpp signaling activation outside of the niche. We show that Tkv functions as Dpp trap/sink to spatially restrain Dpp signaling inside the niche. This self-restrained regulation of niche activity by Tkv in CySCs is independent of the canonical Dpp signaling pathway. Our data demonstrate the critical roles of niche components (CySCs) in the self-restrained regulation of niche activity, which could be shed light on niche activity regulation in general. [ABSTRACT FROM AUTHOR]