核心循环时钟因子Bmal1转化了小鼠心脏中节律性和非节律性基因表达的性别特异性差异
Xiping Zhang1, Spencer B Procopio1, Haocheng Ding2
1Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA.
Function (Oxford, England)
|December 10, 2024
概括
雄性和雌性小鼠的心脏表现出不同的昼夜基因表达模式. 心肌细胞特异性Bmal1损失显著减少了这些性别差异,突出了它在心脏性别特异性基因调节中的作用.
科学领域:
- 心血管生物学 心血管生物学
- 时间生物学 时间生物学
- 分子遗传学 分子遗传学
背景情况:
- 心血管疾病 (CVD) 显示出基于性别的差异.
- 扰乱的昼夜节律与心血管疾病的发展有关.
- 心脏生理时钟的性别差异仍然不太清楚.
研究的目的:
- 研究小鼠心脏昼夜转录组的性别特异性.
- 确定核心昼夜时钟因子Bmal1在特定性别心脏基因表达中的作用.
主要方法:
- 在雄性和雌性小鼠中对心脏昼夜转录组进行比较分析.
- 在成年心肌细胞中Bmal1的有条件淘汰.
- RNA测序以评估基因表达变化.
主要成果:
- 心脏昼夜转录组具有高度的性别特异性,女性更有节律表达基因 (REGs).
- 心肌细胞Bmal1的损失减少了性别差异在REGs和性别之间的整体基因表达.
- 观察到心脏转录因子 (Gata4,Nkx2-5,Tbx5) 的性别特异调节.
结论:
- 特定于心肌细胞的Bmal1对于成年老鼠心脏中特定于性别的基因表达至关重要.
- 昼夜时钟在调解心脏生物学中的性别差异方面发挥着重要作用.
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