LINC01638 维持人体介质干细胞的自我更新和对骨质细胞命运的能力
Jonathan A R Gordon1,2, Coralee E Tye1,2, Bodhisattwa Banerjee1
1Department of Biochemistry, University of Vermont, Burlington, VT, 05405, USA.
Scientific reports
|November 21, 2023
概括
长非编码RNA LINC01638 对于骨发育至关重要. 它的耗尽损害了骨质细胞分化,DNA修复和细胞生长,突出显示了它在骨平衡中的作用.
科学领域:
- 分子生物学分子生物学
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 人类介质干细胞 (hMSCs) 分化成各种细胞类型,包括骨质母细胞用于骨形成.
- 长非编码RNAs (lncRNAs) 是组织发育中的关键表观遗传调节剂,但它们在骨质生成中的作用尚未得到研究.
- LINC01638,一个在hMSCs中高度表达的lncRNA,以前没有对其在骨质生成中的功能进行过研究.
研究的目的:
- 调查LINC01638在调节hMSCs骨质生成和骨质母细胞承诺中的作用.
- 阐明LINC01638影响MSC多能性和骨形成的分子机制.
主要方法:
- 使用CRISPR干扰 (CRISPRi) 来抑制hMSC中的LINC01638表达.
- 通过测量性酸酶表达和其他标记物来评估骨质分化.
- 通过对结尾标签测序 (ChIRP-seq) 采用转录组概况 (RNA-seq) 和染色体相互作用分析来确定分子标和相互作用.
主要成果:
- LINC01638 knockdown 显著抑制了骨质生成,性酸酶表达和骨质细胞分化.
- LINC01638的耗尽导致MSC生长率降低,DNA双链断裂增加,DNA损伤和细胞衰老.
- 在LINC01638耗尽后,RNA-seq揭示了2000多种参与细胞循环,DNA修复和骨质生成途径的mRNA的差异表达.
结论:
- LINC01638对于维持hMSC多能性和调节对骨质细胞系的承诺至关重要.
- 这种lncRNA在促进骨质母细胞分化,细胞生长和DNA完整性方面发挥着关键作用.
- LINC01638是一种新的骨发育和骨组织重塑的调节剂.
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