Wolbachia endosymbionts manipulate the self-renewal and differentiation of germline stem cells to reinforce fertility of their fruit fly host

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(10), P. e3002335 - e3002335

Published: Oct. 24, 2023

The alphaproteobacterium Wolbachia pipientis infects arthropod and nematode species worldwide, making it a key target for host biological control. -driven reproductive manipulations, such as cytoplasmic incompatibility (CI), are credited catapulting these intracellular bacteria to high frequencies in populations. Positive, perhaps mutualistic, manipulations also increase infection frequencies, but not well understood. Here, we identify molecular cellular mechanisms by which influences the molecularly distinct processes of germline stem cell (GSC) self-renewal differentiation. We demonstrate that w Mel rescues fertility flies lacking translational regulator mei-P26 is sufficient sustain infertile homozygous -knockdown stocks indefinitely. Cytology revealed mitigates impact loss through restoring proper pMad, Bam, Sxl, Orb expression. In Oregon R files with wild-type fertility, elevates lifetime egg hatch rates. Exploring phenotypes dual-RNAseq quantification eukaryotic bacterial transcripts offsets many gene expression changes induced at mRNA level. Overall, show beneficially reinforces mRNA, protein, phenotypic levels, may promote emergence mutualism breakdown manipulations.

Language: Английский

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The crosstalk of hedgehog, PI3K and Wnt pathways in diabetes

Archives of Biochemistry and Biophysics, Journal Year: 2020, Volume and Issue: 698, P. 108743 - 108743

Published: Dec. 29, 2020

Language: Английский

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Wnt/β-catenin signalling underpins juvenile Fasciola hepatica growth and development

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(2), P. e1012562 - e1012562

Published: Feb. 7, 2025

Infection by the liver fluke, Fasciola hepatica, places a substantial burden on global agri-food industry and poses significant threat to human health in endemic regions. Widespread resistance limited arsenal of chemotherapeutics, including frontline flukicide triclabendazole (TCBZ), renders F. hepatica control unsustainable accentuates need for novel therapeutic target discovery. A key facet biology is population specialised stem cells which drive growth development - their dysregulation hypothesised represent an appealing avenue control. The exploitation this system as impeded lack understanding molecular mechanisms underpinning development. Wnt signalling pathways govern myriad cell processes during embryogenesis tumorigenesis adult tissues animals. Here, we identify five putative ligands Frizzled receptors fluke transcriptomic datasets find that Wnt/β-catenin most active juveniles, pathogenic life stage. FISH-mediated transcript localisation revealed partitioning ligands, with each displaying distinct expression pattern, consistent regulating different cell/tissue types. silencing individual or gene yielded reductions juvenile worm and, select cases, blunted proliferation neoblast-like cells. Notably, FhCTNNB1, effector signal cascade led aberrant neuromuscular ultimately proved lethal first report RNAi-induced phenotype hepatica. absence any discernible phenotypes following inhibitory destruction complex components low activity rapidly developing worms, corroborates profiles underscores importance driver early-stage fluke. pharmacological inhibition using commercially available inhibitors phenocopied RNAi results provides impetus drug repurposing. Taken together, these data functionally chemically validate targeting strategy undermine pathogenicity

Language: Английский

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Bone Marrow Niches for Skeletal Progenitor Cells and their Inhabitants in Health and Disease

Current Stem Cell Research & Therapy, Journal Year: 2019, Volume and Issue: 14(4), P. 305 - 319

Published: Jan. 24, 2019

The bone marrow hosts skeletal progenitor cells which have most widely been referred to as Mesenchymal Stem or Stromal Cells (MSCs), a heterogeneous population of adult stem possessing the potential for self-renewal and multilineage differentiation. A consensus agreement on minimal criteria has suggested define MSCs in vitro, including adhesion plastic, expression typical surface markers ability differentiate towards adipogenic, osteogenic chondrogenic lineages but they are critically discussed since differentiation capability could not always be confirmed by stringent assays vivo. However, these vitro characteristics led notion that cell populations, similar marrow, reside various tissues. focus numerous (pre)clinical studies tissue regeneration repair. Recent advances terms genetic animal models enabled couple targeting Accordingly, different populations identified nestin leptin receptor. While there still issues with identity of, overlap between specific microenvironments, niches, host maintain marrow. Dynamic mutual interactions through biological physical cues niche constituting inhabitants control dormancy, symmetric asymmetric division lineage commitment. Niche cells, inhabitant their extracellular matrix subject influences aging disease e.g. via cellular modulators. Protective niches can hijacked abused metastasizing tumor may even adapted education. Here, we summarize current knowledge physiology pathophysiology. We discuss plasticity dynamics well future perspectives therapeutic strategies.

Language: Английский

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Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Nov. 2, 2020

Many adult stem cell communities are maintained by population asymmetry, where stochastic behaviors of multiple individual cells collectively result in a balance between division and differentiation. We investigated how this is achieved for Drosophila Follicle Stem Cells (FSCs) spatially-restricted niche signals. FSCs produce transit-amplifying (FCs) from their posterior face quiescent Escort (ECs) to anterior. show that JAK-STAT pathway activity, which declines anterior, dictates the pattern divisions over FSC domain, promotes more locations conversion FCs, while opposing EC production. Wnt activity anterior production, opposes FC The pathways combine define domain through concerted effects on differentiation ECs FCs at either end signaling gradients, impose proliferation matches derivative production.Adult organisms contain variety routinely replaced using can generate specific tissue. These often clustered into small groups, combinations chemical signals nearby encourage each divide or ‘differentiate’ another type cell. different must somehow maintain size shape community. ovary an fruit fly contains group called follicle cells, short. support continual production eggs supplying two types opposite faces cluster: dividing emerge back cluster guide late egg development, non-dividing escort come front early development. Two control graded cluster. strongest territory gradually towards front, absent cells. However, it was unclear gradients these formation To answer question, Melamed Kalderon used genetic engineering modify strength experiments measured affected rate converted found dictated rates, may explain why varies across do not all. also stimulated become opposed Conversely, stronger favored inhibited transitioning This suggests relative helps thecorrect number balancing JAK-STAT, other development many organisms, including humans, have been linked cancer. Therefore, principles mechanisms uncovered apply Furthermore, work highlights changes allow mutant amplify take entire community, play role cancer illnesses.

Language: Английский

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Single-cell RNA sequencing analysis to evaluate antimony exposure effects on cell-lineage communications within the Drosophila testicular niche

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 270, P. 115948 - 115948

Published: Jan. 1, 2024

The increasing production and prevalence of antimony (Sb)-related products raise concerns regarding its potential hazards to reproductive health. Upon environmental exposure, Sb reportedly induces testicular toxicity during spermatogenesis; moreover, it is known affect various cell populations, particularly germline stem populations. However, the cell-cell communication resulting from exposure within niche remains poorly understood. To address this gap, herein we analyzed single-cell RNA sequencing data Sb-exposed Drosophila. Our findings revealed that epidermal growth factor receptor (EGFR) WNT signaling pathways were associated with in Drosophila testes, which may disrupt homeostasis Furthermore, identified several ligand-receptor pairs, facilitating elucidation intercellular crosstalk involved Sb-mediated toxicology. We employed scRNA-seq analysis conducted functional verification investigate expression patterns core downstream factors EGFR signatures testes under influence exposure. Altogether, our results shed light on mechanisms exposure-mediated cell-lineage communications.

Language: Английский

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Dally-like protein sequesters multiple Wnt ligands in the Drosophila germarium

Developmental Biology, Journal Year: 2020, Volume and Issue: 464(1), P. 88 - 102

Published: May 29, 2020

Cells in multicellular organisms rely on secreted ligands for development and morphogenesis. Several mechanisms modulate the availability distribution of ligands, determining their ability to signal locally at long range from source. One these is Dally-like protein (Dlp), a cell-surface glypican that exhibits biphasic functions Drosophila wing discs, promoting Wg signaling long-range source cells inhibiting near cells. In germarium tip ovary, Dlp promotes cap follicle stem However, also expresses other Wnts - Wnt2, Wnt4, Wnt6 function escort promote oogenesis. Whether how local are regulated remains unknown. Here we show dlp overexpression phenotype multifaceted phenocopies multiple Wnt loss-of-function phenotypes. Each aspect suppressed by co-expression individual Wnts, suppression pattern exhibited each suggests have functional specificity germarium. Further, knockdown gain-of-function Together data inhibits Wnt. All four co-immunoprecipitate with S2R+ ​cells, suggesting germarium, sequesters inhibit paracrine signaling. Our results indicate modulates extracellular

Language: Английский

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Blood Vessel Epicardial Substance (BVES) in junctional signaling and cancer

Tissue Barriers, Journal Year: 2018, Volume and Issue: 6(4), P. 1 - 12

Published: Oct. 2, 2018

Blood vessel epicardial substance (BVES) is a tight-junction associated protein that was originally discovered from cDNA screen of the developing heart. Research over last decade has shown not only BVES expressed in cardiac and skeletal tissue, but also throughout gastrointestinal epithelium. Mice lacking sustain worse intestinal injury inflammation. Furthermore, suppressed cancers, mouse modeling loss promotes tumor formation. Recent work multiple laboratories revealed can regulate several molecular pathways, including cAMP, WNT, promoting degradation oncogene, c-Myc. This review will summarize our current understanding how regulates epithelium discuss functions at level to preserve epithelial phenotypes suppress tumorigenesis.

Language: Английский

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Adult stem cells and niche cells segregate gradually from common precursors that build the adult Drosophila ovary during pupal development

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Sept. 30, 2021

Production of proliferative follicle cells (FCs) and quiescent escort (ECs) by stem (FSCs) in adult Drosophila ovaries is regulated niche signals from anterior (cap cells, ECs) posterior (polar FCs) sources. Here we show that ECs, FSCs, FCs develop common pupal precursors, with different fates acquired progressive separation along the AP axis a graded decline cell proliferation. most derive intermingled (IC) precursors interspersed germline cells. Precursors also accumulate to ICs before engulfing naked cyst projected out germarium form first egg chamber polar FC signaling center. Thus, appropriate numbers spatial organization through expansion together establishment cues guide behavior, rather than rigid early specification events.

Language: Английский

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Regulation of N6-Methyladenosine in the Differentiation of Cancer Stem Cells and Their Fate

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Sept. 22, 2020

N6-methyladenosine (m6A) is one of the most common internal RNA modifications in eukaryotes. It a dynamic and reversible process that requires an orchestrated participation methyltransferase, demethylase, methylated binding protein. m6A modification can affect degradation, translation, microRNA processing. plays important role regulation various processes living organisms. In addition to being involved normal physiological such as sperm development, immunity, fat differentiation, cell it also tumor progression stem differentiation. Curiously enough, cancer cells, rare group cells present malignant tumors, retain characteristics play survival, proliferation, metastasis, recurrence cancers. Recently, studies demonstrated participates self-renewal pluripotent these cells. However, considering multiple targets are different processes, exact remains controversial. This article focuses on mechanism its effects differentiation provide basis for elucidating tumorigenesis mechanisms exploring new potential therapeutic approaches.

Language: Английский

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