Redox Homeostasis Plays Important Roles in the Maintenance of the Drosophila Testis Germline Stem Cells

Tan, Si Heng Sharon; Lee, Qian Ying; Wong, Belinda Shu Ee; Cai, Yu; Baeg, Gyeong Hun

doi:10.1016/j.stemcr.2017.05.034

Cited by 39 publications

(44 citation statements)

References 59 publications

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“…1 G, G’ and K, arrows). All these findings are in accordance with our previous observation that high levels of ROS induced by the oxidant paraquat promote GSC differentiation [18] , and suggest that testes with elevated ROS by ND75 knockdown can be utilized for genome-wide studies to identify the downstream effectors of high ROS-induced GSC differentiation.…”

Section: Resultssupporting

confidence: 92%

“…Oxidative stress has been shown to influence stem cell behavior by facilitating the proliferation, differentiation or apoptosis of stem cell populations [1] . In the Drosophila testis, redox states regulated by Keap1/Nrf2 activity play important roles in GSC maintenance [18] . In an attempt to identify molecules that are associated with GSC differentiation induced by high levels of ROS, we first confirmed the effects of increased intracellular ROS levels by knocking down ND75 on GSC homeostasis.…”

Section: Resultsmentioning

confidence: 99%

“…The Drosophila testis germline stem cell (GSC) system is one of the best understood adult stem cell models for studying and understanding the fundamental cellular mechanisms of stem cell behavior, as stem cells and their progenies can be easily identified, traced, imaged and genetically manipulated in vivo [17] . Importantly, we previously showed that high levels of ROS facilitate GSC differentiation through the activation of EGFR signaling, whereas decreased ROS levels conversely promote the proliferation of GSC-like cells in the Drosophila testes [18] . In this study, we performed Affymetrix microarray analysis using the Drosophila testes to identify the downstream effectors of ROS-mediated GSC differentiation.…”

Section: Introductionmentioning

confidence: 97%

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Small Maf functions in the maintenance of germline stem cells in the Drosophila testis

et al. 2018

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Reactive oxygen species (ROS) are byproducts generated during normal cellular metabolism, and redox states have been shown to influence stem cell self-renewal and lineage commitment across phyla. However, the downstream effectors of ROS signaling that control stem cell behavior remain largely unexplored. Here, we used the Drosophila testis as an in vivo model to identify ROS-induced effectors that are involved in the differentiation process of germline stem cells (GSCs). In the Affymetrix microarray analysis, 152 genes were either upregulated or downregulated during GSC differentiation induced by elevated levels of ROS, and a follow-up validation of the gene expression by qRT-PCR showed a Spearman's rho of 0.9173 (P<0.0001). Notably, 47 (31%) of the identified genes had no predicted molecular function or recognizable protein domain. These suggest the robustness of this microarray analysis, which identified many uncharacterized genes, possibly with an essential role in ROS-induced GSC differentiation. We also showed that maf-S is transcriptionally downregulated by oxidative stress, and that maf-S knockdown promotes GSC differentiation but Maf-S overexpression conversely results in an over-growth of GSC-like cells by promoting the mitotic activity of germ cell lineage. Together with the facts that Maf-S regulates ROS levels and genetically interacts with Keap1/Nrf2 in GSC maintenance, our study suggests that Maf-S plays an important role in the Drosophila testis GSC maintenance by participating in the regulation of redox homeostasis.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Small Maf functions in the maintenance of germline stem cells in the Drosophila testis

et al. 2018

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“…AOX expression may also affect ROS signaling, although any such effect would only be meaningful in combination with specific stresses arising from the low-nutrient diet. ROS is recognized as a regulator of stemness (Perales-Clemente, Folmes, & Terzic, 2014) and, in Drosophila, influences embryogenesis (Xie et al, 2010), imaginal disc regeneration (Khan, Abidi, Skinner, Tian, & Smith-Bolton, 2017), and testis differentiation (Tan, Lee, Wong, Cai, & Baeg, 2017).…”

Section: Mechanism Of Developmental Failure Of Aox-expressing Fliesmentioning

confidence: 99%

Alternative oxidase confers nutritional limitation on Drosophila development

et al. 2019

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The mitochondrial alternative oxidase, AOX, present in most eukaryotes apart from vertebrates and insects, catalyzes the direct oxidation of ubiquinol by oxygen, by‐passing the terminal proton‐motive steps of the respiratory chain. Its physiological role is not fully understood, but it is proposed to buffer stresses in the respiratory chain similar to those encountered in mitochondrial diseases in humans. Previously, we found that the ubiquitous expression of AOX from Ciona intestinalis in Drosophila perturbs the development of flies cultured under low‐nutrient conditions (media containing only glucose and yeast). Here we tested the effects of a wide range of nutritional supplements on Drosophila development, to gain insight into the physiological mechanism underlying this developmental failure. On low‐nutrient medium, larvae contained decreased amounts of triglycerides, lactate, and pyruvate, irrespective of AOX expression. Complex food supplements, including treacle (molasses), restored normal development to AOX‐expressing flies, but many individual additives did not. Inhibition of AOX by treacle extract was excluded as a mechanism, since the supplement did not alter the enzymatic activity of AOX in vitro. Furthermore, antibiotics did not influence the organismal phenotype, indicating that commensal microbes were not involved. Fractionation of treacle identified a water‐soluble fraction with low solubility in ethanol, rich in lactate and tricarboxylic acid cycle intermediates, which contained the critical activity. We propose that the partial activation of AOX during metamorphosis impairs the efficient use of stored metabolites, resulting in developmental failure.

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“…The cell biology of cell fate decisions Sumitra Tatapudy et al differentiation and mouse spermatogonial stem cell self-renewal, increased ROS levels activate p38 MAPK signaling pathway, which promotes the transcription of serum response factor (SRF), and ultimately increases the activity of differentiation proteins, such as aactin and calponin [73]. Additionally, high levels of ROS in Drosophila GSCs promote differentiation by increasing the transcription of the epidermal growth factor receptor ligand, Spitz, thereby activating the MAPK signaling pathway [69]. Collectively, these studies demonstrate that ROS concentrations are tightly controlled during cellular differentiation and that changes in ROS concentrations play important roles in the cell fate decision process.…”

Section: Embo Reportsmentioning

confidence: 99%

Cell fate decisions: emerging roles for metabolic signals and cell morphology

et al. 2017

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Understanding how cell fate decisions are regulated is a fundamental goal of developmental and stem cell biology. Most studies on the control of cell fate decisions address the contributions of changes in transcriptional programming, epigenetic modifications, and biochemical differentiation cues. However, recent studies have found that other aspects of cell biology also make important contributions to regulating cell fate decisions. These cues can have a permissive or instructive role and are integrated into the larger network of signaling, functioning both upstream and downstream of developmental signaling pathways. Here, we summarize recent insights into how cell fate decisions are influenced by four aspects of cell biology: metabolism, reactive oxygen species (ROS), intracellular pH (pHi), and cell morphology. For each topic, we discuss how these cell biological cues interact with each other and with protein-based mechanisms for changing gene transcription. In addition, we highlight several questions that remain unanswered in these exciting and relatively new areas of the field.

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Redox Homeostasis Plays Important Roles in the Maintenance of the Drosophila Testis Germline Stem Cells

Cited by 39 publications

References 59 publications

Small Maf functions in the maintenance of germline stem cells in the Drosophila testis

Small Maf functions in the maintenance of germline stem cells in the Drosophila testis

Alternative oxidase confers nutritional limitation on Drosophila development

Cell fate decisions: emerging roles for metabolic signals and cell morphology

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