乙-CoA是脏原生细胞池维护的关键分子
Fabiola Diniz1, Nguyen Yen Nhi Ngo1, Mariel Colon-Leyva1
1Section of Pediatric Nephrology, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
Nature communications
|November 25, 2023
概括
乙-CoA代谢对于脏发育至关重要. 操纵这种途径,特别是酸,可以维持脏前代细胞,并可能预防成人脏疾病.
科学领域:
- 发育生物学 发展生物学
- 代谢生物化学 代谢生物化学
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 出生时的脏赋予对于长期的脏和心血管健康至关重要.
- 原细胞 (NPC) 的命运受糖解的影响,但机制尚不清楚.
研究的目的:
- 阐明糖解调节影响NPC命运的机制.
- 调查乙-CoA代谢在脏发育和产生的作用.
主要方法:
- 结合RNA测序和定量蛋白质组学,以识别NPC中Wnt激活或糖解抑制的向基因.
- 在小鼠模型中利用了Six2Cre介导的ATP-酸酶 (Acly) 和酸补充的删除.
主要成果:
- 鉴定了267个常受Wnt激活或糖解抑制影响的基因,聚合在乙-CoA.
- 糖解抑制降低了Mevalonate/胆固醇通路基因的调节,并促进了NPC的分化.
- 酸补充剂挽救了糖解抑制效应,并抵消了Acly删除影响.
- 阿克利删除导致NPC池耗尽,减少质细胞数量,增加Wnt4表达.
结论:
- 乙-CoA代谢在脏发育中起着关键作用.
- 向乙-CoA代谢提供了操纵产生的潜在策略.
- 这些发现可能会导致预防成人病的新方法.
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