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揭示人脂肪干细胞成脂和成骨分化第一天多核糖体长非编码 RNA 的表达。

Unveiling Polysomal Long Non-Coding RNA Expression on the First Day of Adipogenesis and Osteogenesis in Human Adipose-Derived Stem Cells.

机构信息

Stem Cell Basic Biology Laboratory (LABCET), Carlos Chagas Institute-Fiocruz/PR, Curitiba 81350-010, PR, Brazil.

Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

出版信息

Int J Mol Sci. 2024 Feb 7;25(4):2013. doi: 10.3390/ijms25042013.

Abstract

Understanding the intricate molecular mechanisms governing the fate of human adipose-derived stem cells (hASCs) is essential for elucidating the delicate balance between adipogenic and osteogenic differentiation in both healthy and pathological conditions. Long non-coding RNAs (lncRNAs) have emerged as key regulators involved in lineage commitment and differentiation of stem cells, operating at various levels of gene regulation, including transcriptional, post-transcriptional, and post-translational processes. To gain deeper insights into the role of lncRNAs' in hASCs' differentiation, we conducted a comprehensive analysis of the lncRNA transcriptome (RNA-seq) and translatome (polysomal-RNA-seq) during a 24 h period of adipogenesis and osteogenesis. Our findings revealed distinct expression patterns between the transcriptome and translatome during both differentiation processes, highlighting 90 lncRNAs that are exclusively regulated in the polysomal fraction. These findings underscore the significance of investigating lncRNAs associated with ribosomes, considering their unique expression patterns and potential mechanisms of action, such as translational regulation and potential coding capacity for microproteins. Additionally, we identified specific lncRNA gene expression programs associated with adipogenesis and osteogenesis during the early stages of cell differentiation. By shedding light on the expression and potential functions of these polysome-associated lncRNAs, we aim to deepen our understanding of their involvement in the regulation of adipogenic and osteogenic differentiation, ultimately paving the way for novel therapeutic strategies and insights into regenerative medicine.

摘要

理解调控人类脂肪来源干细胞(hASCs)命运的复杂分子机制对于阐明健康和病理条件下脂肪生成和骨生成分化之间的微妙平衡至关重要。长非编码 RNA(lncRNA)已成为涉及干细胞谱系决定和分化的关键调节因子,在基因调控的各个层面发挥作用,包括转录、转录后和翻译后过程。为了更深入地了解 lncRNA 在 hASCs 分化中的作用,我们对脂肪生成和骨生成过程中 24 小时的 lncRNA 转录组(RNA-seq)和翻译组(多核糖体-RNA-seq)进行了全面分析。我们的研究结果揭示了在这两种分化过程中转录组和翻译组之间的独特表达模式,突出了 90 个仅在多核糖体部分受到调控的 lncRNA。这些发现强调了研究与核糖体相关的 lncRNA 的重要性,因为它们具有独特的表达模式和潜在的作用机制,如翻译调控和微蛋白的潜在编码能力。此外,我们还鉴定了细胞分化早期与脂肪生成和骨生成相关的特定 lncRNA 基因表达程序。通过阐明这些多核糖体相关 lncRNA 的表达和潜在功能,我们旨在加深对它们在脂肪生成和骨生成分化调控中的参与的理解,最终为新型治疗策略和再生医学的新见解铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3de/10888724/6d4d39e46994/ijms-25-02013-g001.jpg

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