Cross-Species Insights from Single-Nucleus Sequencing Highlight Aging-Related Hippocampal Features in Tree Shrew

Molecular Biology and Evolution, Journal Year: 2025, Volume and Issue: 42(2)

Published: Feb. 1, 2025

The tree shrew brain has garnered considerable attention due to its remarkable similarities human brain. However, the cellular composition and genetic signatures of hippocampus across postnatal life remain poorly characterized. Here, we establish first single-nucleus transcriptomic atlas spanning life, detailing dynamics diversity neurogenic lineage, oligodendrocytes, microglia, endothelial cells. Notably, cross-species comparison among humans, macaques, shrews, mice reveals that transcriptome resembles making it a promising model for simulating neurological diseases. More interestingly, identified unique class shrew-specific neural stem cells established SOX6, ADAMTS19, MAP2 as their markers. Furthermore, aberrant gene expression dysfunction in are linked neuroinflammation cognitive impairment during aging. Our study provides extensive resources on cell profiles, serving foundation future research neurodevelopmental disorders shrews.

Language: Английский

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NF2 loss malignantly transforms human pancreatic acinar cells and enhances cell fitness under environmental stress

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 3, 2025

ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor permissive genetic mutations, nature cellular origin and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed CRISPR knockout screen targeting 199 previously underappreciated potential suppressors curated from clinical PDAC samples. Our data revealed significant enrichment list candidates, with NF2 emerging top target. Functional validation confirmed that loss promotes transition to an invasive state, potentially through extracellular matrix modulation. inactivation was found enhance cell fitness under nutrient starvation. This adaptation not only reinforces oncogenic state but also confers therapeutical resistance. Additionally, is associated fibroblast heterogeneity cancer-stroma communications in evolution. These findings establish critical suppressor uncover its role mediating drug Importantly, study provides new insights into resistance mechanisms therapeutic targets PDAC.

Language: Английский

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The Liver-Enriched Long Non-Coding RNA FAM99A Suppresses Tumorigenesis through Negative Regulation of Protein Synthesis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 4, 2025

ABSTRACT Primary liver cancer represents a significant global health burden, with limited therapeutic options for advanced disease. Long non-coding RNAs (lncRNAs) are increasingly found to play crucial roles in hepatic biology and disease progression. Here, we identify FAM99A as highly liver-specific lncRNA that is systematically downregulated across malignancies, reduced expression correlating poor clinical outcomes. exhibits remarkable tissue specificity minimal outside the liver, its levels rapidly decline during primary hepatocyte dedifferentiation culture. Through isoform analysis, establish FAM99A-203 predominant transcript normal observe altered distribution cancers. Functionally, overexpression inhibits anchorage-independent growth cell lines. Transcriptomic analysis reveals negatively regulates translation-related pathways both cells hepatocytes. This corroborated by protein synthesis assays showing substantially reduces translation rates. Targeted RNase H-mediated extraction coupled mass spectrometry identifies multiple components of machinery direct binding partners, including eukaryotic initiation factors RNA helicases involved ribosome biogenesis. Clinical data demonstrates inverse correlations between ribosomal genes patients. Additionally, hepatitis B virus appears downregulate expression, potentially contributing oncogenic properties. Our findings translational regulator exerts tumor-suppressive effects restraining rates, offering insights into hepatocarcinogenesis potential biomarker agent new avenues.

Language: Английский

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Comprehensive phosphoproteomic profiling of the signaling network in mesenchymal stem cells upon dimethyl fumarate treatment

Journal of Analytical Science & Technology, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 20, 2025

Abstract Mesenchymal stem cells (MSCs), recognized as a promising candidate for treating degenerative diseases, have garnered significant attention from scientists in recent decades. However, notable concern associated with MSCs is their low stability and viability. In previous study, we found that dimethyl fumarate (DMF) at 10 μM concentration can enhance the proliferation of increase stability. this research, performed protein extraction digestion on both DMF-treated MSCs, subsequently enriching phosphorylated peptides using TiO 2 identifying them through nanoLC-MS/MS, data analysis carried out MaxQuant Perseus. The results revealed 837 peptides, which 559 exhibited elevated expression levels compared to untreated MSCs. These phosphopeptides corresponded 466 340 phosphoproteins, respectively. Furthermore, network upregulated Reactome identified RNA Binding Motif Protein 39 potentially crucial mediating cellular responses, influencing processing events contributing regulation gene expression. This study underscores impact DMF treatment phosphoproteome Further investigations into these pathways could illuminate novel therapeutic strategies clinical efficacy MSC-based treatments.

Language: Английский

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