A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals nonhierarchical model of development

Science Advances, Journal Year: 2023, Volume and Issue: 9(14)

Published: April 7, 2023

The specialized cell types of the mucociliary epithelium (MCE) lining respiratory tract enable continuous airway clearing, with its defects leading to chronic diseases. molecular mechanisms driving fate acquisition and temporal specialization during epithelial development remain largely unknown. Here, we profile developing Xenopus MCE from pluripotent mature stages by single-cell transcriptomics, identifying multipotent early progenitors that execute multilineage cues before specializing into late-stage ionocytes goblet basal cells. Combining in silico lineage inference, situ hybridization, multiplexed RNA imaging, capture initial bifurcation multiciliated chart type emergence progression types. Comparative analysis nine atlases reveals an evolutionary conserved transcriptional module ciliated cells, whereas secretory distinct function-specific programs across vertebrates. We uncover a nonhierarchical model alongside data resource for understanding biology.

Language: Английский

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Retinal disease in ciliopathies: Recent advances with a focus on stem cell-based therapies

Translational Science of Rare Diseases, Journal Year: 2019, Volume and Issue: 4(1-2), P. 97 - 115

Published: July 4, 2019

Ciliopathies display extensive genetic and clinical heterogeneity, varying in severity, age of onset, disease progression organ systems affected. Retinal involvement, as demonstrated by photoreceptor dysfunction or death, is a highly penetrant phenotype among vast majority ciliopathies. Photoreceptor cells possess specialized modified sensory cilium with membrane discs where efficient photon capture ensuing signaling cascade initiate the visual process. Disruptions cilia biogenesis protein transport lead to impairment function eventually degeneration. Despite advances elucidation ciliogenesis defects, we have limited understanding pathogenic mechanisms underlying retinal phenotype(s) observed human Patient-derived induced pluripotent stem cell (iPSC)-based approaches offer unique opportunity complement studies model organisms examine relevant humans. Three-dimensional organoids from iPSC lines feature laminated cytoarchitecture, apical-basal polarity emergence ciliary structure, thereby permitting modeling photoreceptors vitro. Here, review biology associated defects discuss recent progress evolving treatment modalities, especially using patient-derived iPSCs, for

Language: Английский

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Motile cilia genetics and cell biology: big results from little mice

Cellular and Molecular Life Sciences, Journal Year: 2020, Volume and Issue: 78(3), P. 769 - 797

Published: Sept. 11, 2020

Language: Английский

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Antibodies, Nanobodies, or Aptamers—Which Is Best for Deciphering the Proteomes of Non-Model Species?

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(7), P. 2485 - 2485

Published: April 3, 2020

This planet is home to countless species, some more well-known than the others. While we have developed many techniques be able interrogate of "omics", proteomics becoming recognized as a very important part puzzle, given how protein functional cell. Within human health, proteome fairly well-established, with numerous reagents being available decipher cellular pathways. Recent research advancements assisted in characterizing proteomes model (non-human) however, other are only just touching surface. review considers three main reagent classes-antibodies, aptamers, and nanobodies-as means continuing investigate non-model species without complications understanding full signature species. Considerations ease production, potential applications, necessity for producing new depending on homology presented.

Language: Английский

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Advances in the Xenopus immunome: Diversification, expansion, and contraction

Developmental & Comparative Immunology, Journal Year: 2023, Volume and Issue: 145, P. 104734 - 104734

Published: May 10, 2023

Language: Английский

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Xenopus laevis (Daudin, 1802) as a Model Organism for Bioscience: A Historic Review and Perspective

Biology, Journal Year: 2023, Volume and Issue: 12(6), P. 890 - 890

Published: June 20, 2023

In vitro systems have been mainly promoted by authorities to sustain research following the 3Rs principle, but continuously increasing amounts of evidence point out that in vivo experimentation is also extreme relevance. Xenopus laevis, an anuran amphibian, a significant model organism study evolutionary developmental biology, toxicology, ethology, neurobiology, endocrinology, immunology and tumor biology; thanks recent development genome editing, it has acquired relevant position field genetics. For these reasons, X. laevis appears be powerful alternative zebrafish for environmental biomedical studies. Its life cycle, as well possibility obtain gametes from adults during whole year embryos fertilization, allows experimental studies several biological endpoints, such gametogenesis, embryogenesis, larval growth, metamorphosis and, course, young adult stages. Moreover, with respect invertebrate even vertebrate animal models, displays higher degree similarity mammals. Here, we reviewed main available literature on use biosciences inspired Feymann’s revised view, “Plenty room biology at bottom,” suggest very useful all possible

Language: Английский

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Mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting DNA damage

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116434 - 116434

Published: March 20, 2024

The cilium is a microtubule-based organelle that plays pivotal role in embryonic development and maintenance of physiological functions the human body. In addition to their function as sensors transduce diverse extracellular signals, including growth factors, fluid flow, physical forces, cilia are intricately involved cell cycle regulation preservation DNA integrity, formation resorption dynamics tightly linked progression. Recently, several studies have defects specific ciliary proteins damage response. However, it remains unclear whether how primary contribute cancer development. Mebendazole (MBZ) an anthelmintic drug with anticancer properties some cells. MBZ continuously being tested for clinical studies, but precise mechanism its activities unknown. Here, using Xenopus laevis embryos model system, we discovered significantly hinders induces damage. Remarkably, cilium-bearing cells exhibited heightened vulnerability combined treatment conventional drugs. Our findings shed light on influence cilia, rather than cytosolic microtubules, triggering damage, elucidating previously unidentified underlying potential MBZ-mediated therapy.

Language: Английский

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Rare Human Diseases: Model Organisms in Deciphering the Molecular Basis of Primary Ciliary Dyskinesia

Cells, Journal Year: 2019, Volume and Issue: 8(12), P. 1614 - 1614

Published: Dec. 11, 2019

Primary ciliary dyskinesia (PCD) is a recessive heterogeneous disorder of motile cilia, affecting one per 15,000–30,000 individuals; however, the frequency this likely underestimated. Even though more than 40 genes are currently associated with PCD, in case approximately 30% patients, genetic cause manifested PCD symptoms remains unknown. Because cilia highly evolutionarily conserved organelles at both proteomic and ultrastructural levels, analyses unicellular multicellular model organisms can help not only to identify new proteins essential for motility (and thus putative PCD-causative genes), but also elucidate function encoded by known genes. Consequently, studies involving us understand molecular mechanism(s) behind phenotypic changes observed affected patients. Here, we summarize current state art genetics biology emphasize impact conducted using on existing knowledge.

Language: Английский

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Interaction between perfluoro‐octanoic sulfonate and common antibiotics induces developmental anomalies and lethality in Xenopus laevis

Developmental Dynamics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Abstract Background Perfluoroalkyl substances (PFAS) are persistent environmental contaminants previously used for industrial purposes as a non‐stick coating and flame retardant. The stability of these molecules prevents their breakdown, which results in ground water contamination across the globe. known to bioaccumulate various organisms. However, health consequences remain unclear due large number PFAS family different effects on tissues. Here, we use frog Xenopus laevis investigate developmental exposure molecule perfluoro‐octanoic sulfonate (PFOS). Results We find that high levels PFOS significant axial shortening developing tadpoles. Further, dose‐dependent formation cellular mass dorsal fin. Unexpectedly, found phenotypes exacerbated upon co‐exposure with commonly antibiotics. Specifically, gentamicin co‐treatment increased apoptosis, loss integrity, overall lethality. Conclusions Our suggest mechanism whereby reaches toxic mitochondria only presence PFOS. These findings add our understanding vertebrate development present an added concern potential interactions

Language: Английский

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Assessing species bias in amphibian research on endocrine disruptors: beyond Xenopus laevis

Frontiers in Environmental Science, Journal Year: 2025, Volume and Issue: 13

Published: May 14, 2025

Due to their high sensitivity hormonal agents, in recent years, amphibians have been proposed as bioindicators for the presence of endocrine-disrupting compounds (EDCs) environment. EDCs are a chemically diverse group compounds, mainly anthropogenic origin, that can interfere with hormone receptors. The escalating global environmental pollution poses significant threat wildlife and human health. Amphibians at risk exposure environment, they produce eggs without protective shell, possess highly permeable skin, most them undergo an aquatic life phase, where chronically exposed water. This raises concerns about contribution dramatic decline amphibian populations underscores necessity environmental-relevant studies this area. Despite critical need, attracted relatively little research focus regard. Although above 200 experimental on topic sex, reproduction, related traits conducted, portion rely model species from Xenopus genus, which do not fully represent amphibians. Additionally, these often use strict laboratory conditions fail mimic natural scenarios. Our extensive review highlights gaps emphasizes importance incorporating broader range understand true impact EDCs. We advocate more environmentally relevant settings native enhance ecological validity findings.

Language: Английский

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