The Transmitter, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Язык: Английский
Cell Reports, Год журнала: 2024, Номер 43(6), С. 112787 - 112787
Опубликована: Май 28, 2024
Protein aggregation, which can sometimes spread in a prion-like manner, is hallmark of neurodegenerative diseases. However, whether aggregates form during normal brain aging remains unknown. Here, we use quantitative proteomics the African turquoise killifish to identify protein that accumulate old vertebrate brains. These are enriched for RNA-binding proteins, notably ATP-dependent RNA helicase DDX5. We validate DDX5 forms aggregate-like puncta brains and mice. Interestingly, DDX5's domain allows these propagate across many generations yeast. In vitro, phase separates into condensates. Mutations abolish prion propagation also impair protein's ability separate. condensates exhibit enhanced enzymatic activity, but they mature inactive, solid aggregates. Our findings suggest with properties aging, could have implications age-dependency cognitive decline.
Язык: Английский
Процитировано
16
Science, Год журнала: 2024, Номер 384(6700), С. 1105 - 1110
Опубликована: Июнь 6, 2024
Axis formation in fish and amphibians typically begins with a prepattern of maternal gene products. Annual killifish embryogenesis, however, challenges prepatterning models as blastomeres disperse then aggregate to form the germ layers body axes. We show that huluwa , factor thought break symmetry by stabilizing β-catenin, is truncated inactive Nothobranchius furzeri . Nuclear β-catenin not selectively stabilized on one side blastula but accumulates cells forming aggregate. Blocking activity or Nodal signaling disrupts layer specification. coordinates cell migration, establishing an early role for this pathway. These results reveal surprising departure from established mechanisms axis formation: Huluwa-mediated dispensable, regulate morphogenesis.
Язык: Английский
Процитировано
6
Development, Год журнала: 2024, Номер 151(9)
Опубликована: Май 1, 2024
Animal evolution is influenced by the emergence of new cell types, yet our understanding this process remains elusive. This prompts need for a broader exploration across diverse research organisms, facilitated recent breakthroughs, such as gene editing tools and single-cell genomics. Essential to type accurate identification homologous cells. We delve into significance considering developmental ontogeny potential pitfalls when drawing conclusions about homology. Additionally, we highlight discoveries in study through application transcriptomics pinpoint areas ripe further exploration.
Язык: Английский
Процитировано
5
Aging Cell, Год журнала: 2024, Номер 23(8)
Опубликована: Май 14, 2024
Abstract Age‐related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of on homeostasis, we used short‐lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) hallmarks loss. Bulk single‐cell RNA‐sequencing (scRNAseq) three age groups (6‐, 12‐, 18‐week‐old) identified transcriptional fingerprints killifish retina, unveiling pathways also aged brain, including oxidative stress, gliosis, inflammageing. These findings were comparable observations mouse retina. Additionally, changes genes related diseases, such as glaucoma age‐related macular degeneration, observed. The cellular heterogeneity retina was characterized, confirming presence all typical vertebrate cell types. Data integration from age‐matched samples between bulk scRNAseq experiments revealed specificity gene expression upon ageing, suggesting potential disruption homeostasis. Differential analysis within types highlighted role glial/immune cells important stress regulators during ageing. Our work emphasizes value fast‐ageing elucidating signatures age‐associated disease decline. This study contributes understanding how may CNS health, providing insights that inform future therapeutic strategies for pathologies.
Язык: Английский
Процитировано
5
Neuron, Год журнала: 2025, Номер 113(1), С. 82 - 108
Опубликована: Янв. 1, 2025
SummaryBrain aging leads to a decline in cognitive function and concomitant increase the susceptibility neurodegenerative diseases such as Alzheimer's Parkinson's diseases. A key question is how changes within individual cells of brain give rise age-related dysfunction. Developments single-cell "omics" technologies, transcriptomics, have facilitated high-dimensional profiling cells. These technologies led new comprehensive characterizations at resolution. Here, we review insights gleaned from omics studies aging, starting with cell-type-centric overview age-associated followed by discussion cell-cell interactions during aging. We highlight provide an unbiased view different rejuvenation interventions comment on promise combinatorial approaches for brain. Finally, propose directions, including models neural stem focal point rejuvenation.
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Фев. 26, 2025
Regulators of chromatin accessibility play key roles in cell fate transitions, triggering onset novel transcription programs as cells differentiate. In the Drosophila male germ line stem lineage, tMAC, a master regulator spermatocyte differentiation that binds thousands loci, is required for local opening chromatin, allowing activation spermatocyte-specific promoters. Here we show cell-type specific surveillance system involving multiple zinc finger protein Kmg and pipsqueak domain Dany dampens transcriptional output from weak tMAC dependent promoters blocks binding at additional cryptic promoters, thus preventing massive expression aberrant protein-coding transcripts. ChIP-seq showed enriched tMAC-bound it repressed, consistent with direct action. contrast, did not repress highly expressed genes, where they colocalized their partner, modeler Mi-2 (NuRD), along transcribed regions rather than promoter. has been shown to preferentially bind RNA over (Ullah et al . 2022). We propose genes abundant nascent pulls Kmg/Dany complex away providing mechanism effectively ectopic while protecting robust transcription.
Язык: Английский
Процитировано
0
Biogerontology, Год журнала: 2025, Номер 26(2)
Опубликована: Март 14, 2025
Abstract The orexinergic system is anatomically and functionally conserved in almost all vertebrates, the role healthy ageing age-associated diseases has been studied mammals. Here, we review main findings on age-related regulation of mammals, including human patients highlights how fish Nothobranchius furzeri serves as an exceptional model to spearhead research unravel intricate mechanisms underlying during ageing. brain this teleost characterized by presence neurodegenerative processes similar those associated with pathologies rather than We present in-depth summary discussion groundbreaking advances understanding neuroanatomical organization system, its pivotal mammalian models, profound involvement diseases.
Язык: Английский
Процитировано
0
Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(20)
Опубликована: Май 16, 2025
The switch from precursor cell proliferation to onset of differentiation in adult stem lineages must be carefully regulated produce sufficient progeny maintain and repair tissues, yet prevent overproliferation that may enable oncogenesis. In the Drosophila male germ lineage, spermatogonia produced by line cells undergo a limited number transit amplifying mitotic divisions before switching spermatocyte program sets up meiosis eventual spermatid differentiation. is set accumulation bag-of-marbles (Bam) protein critical threshold. bam mutants, proliferate through several extra rounds mitosis then die without becoming spermatocytes. Here, we show key role Bam for repressing expression Held Out Wings ( how ), homolog mammalian Quaking. Knockdown was allow mutant or its partner benign gonial neoplasm differentiate, while forced nuclear-targeted How wild-type resulted continued at expense Our findings suggest targets RNA degradation acting as an adapter recruit CCR4-NOT deadenylation complex via binding subunit, Caf40. As itself RNA-binding with roles processing, our reveal lineage cascade proteins.
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Май 1, 2023
Abstract Aging is accompanied by a progressive loss of tissue homeostasis, including declining stem-cell function and increased cancer susceptibility. The naturally short-lived African turquoise killifish has emerged as powerful system for investigating vertebrate aging. However, critical mass advanced genetic tools mechanistic studies been largely missing. Here, we develop the Killibow , multispectral transgenic line life-long lineage tracing, an immunocompromised rag2 mutant transplantation studies, mutants genomic instability (i.e. atm tp53 ). We performed series experiments using this platform, tracing following germline transplantation, identifying occurring age-related melanoma engraftment into mutants. Exploring tumor dynamics reveals intriguing interplay between adaptive immunity, evolutionarily conserved decline in immune functions. Together, toolkit streamlines investigation molecular mechanisms underlying homeostasis during aging disease.
Язык: Английский
Процитировано
7
Journal of Comparative Physiology A, Год журнала: 2024, Номер 210(2), С. 325 - 346
Опубликована: Фев. 27, 2024
Abstract For 100 years, the Journal of Comparative Physiology-A has significantly supported research in field neuroethology. The celebration journal’s centennial is a great time point to appreciate recent progress neuroethology and discuss possible avenues field. Animal behavior main source inspiration for neuroethologists. This illustrated by huge diversity investigated behaviors species. To explain at mechanistic level, neuroethologists combine neuroscientific approaches with sophisticated behavioral analysis. rapid technological neuroscience makes highly dynamic exciting research. summarize scientific neuroethology, I went through all abstracts last six International Congresses Neuroethology (ICNs 2010–2022) categorized them based on sensory modalities, experimental model species, topics. highlights gives us perspective field’s future. At end, highlight three topics that may, among others, influence future hope sharing my roots may inspire other scientists follow neuroethological approaches.
Язык: Английский
Процитировано
2