对纵向和横向拉伸的不同敏感性介导了小鼠新生儿心室肌细胞的转录反应
Shulin Cao1, Kyle S Buchholz1, Philip Tan2
1Department of Bioengineering, University of California San Diego, La Jolla, California, United States.
American journal of physiology. Heart and circulatory physiology
|December 8, 2023
概括
异型拉伸显著影响心肌细胞基因表达,纵向拉伸导致比横向拉伸更大的转录反应. 这种差异主要是由于细胞敏感度的变化,而不是不同的信号通路.
科学领域:
- 心血管生物学 心血管生物学
- 机械生物学 机械生物学
- 分子细胞生物学 分子细胞生物学
背景情况:
- 心肌细胞机械敏感信号通路对于心脏功能和适应至关重要.
- 了解异构拉伸如何调节这些通路对于破译心脏对机械负荷的反应至关重要.
研究的目的:
- 通过异性拉伸来研究心肌细胞机械敏感信号通路的差异调节.
- 确定负责不同对纵向与横向拉伸的转录反应的潜在机制.
主要方法:
- 微模式的新生小鼠心肌细胞被静态纵向或横向的异型拉伸.
- 使用RNA测序 (RNA-seq) 来测量差异性基因表达.
- 开发并验证了基于逻辑的心肌细胞机制信号的普通微分方程模型.
主要成果:
- 与横向拉伸 (30个基因) 相比,纵向拉伸诱导的差异性基因表达显著增加 (557个基因).
- 开发的模型准确地预测了测量的表达变化 (69%的准确性) 和发布的数据 (63-91%的准确性).
- 响应的差异归因于对纵向拉伸的敏感度大约是两倍,而不是差异性通路激活.
结论:
- 心肌细胞基因表达对与肌纤维导向相对的异性拉伸轴高度敏感.
- 转录反应的大小主要取决于拉伸灵敏度,纵向负荷更强.
- 这一发现为心脏基因表达的机制调节和潜在的治疗点提供了关键的见解.
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