基质刚性决定了WI-38细胞在增殖停止的独特途径
Alyssa M Kaiser1, Amirali Selahi1, Wenjun Kong1
1Calico Life Sciences LLC, South San Francisco, USA.
GeroScience
|September 20, 2025
概括
细胞机械环境影响复制寿命. 更软的基质缩短细胞增殖并诱导衰老,这个过程由端粒酶逆转录酶 (hTERT) 逆转.
科学领域:
- 细胞生物学 细胞生物学
- 机械生物学 机械生物学
- 衰老研究研究 衰老研究
背景情况:
- 有限的复制潜力是体细胞的标志,通过端粒缩短导致复制性衰老.
- 端粒酶逆转录酶 (hTERT) 可以克服复制性停止.
- 机械传导通路,如YAP信号传导,在细胞接近衰老时被激活,但它们在复制寿命中的作用尚不清楚.
研究的目的:
- 研究机械环境,特别是基质刚度如何影响WI-38人类肺纤维细胞的复制寿命和衰老轨迹.
- 探索机械感知与端粒驱动的复制性停止之间的相互作用.
主要方法:
- 在不同硬度的基板上培养WI-38细胞.
- 分析了增殖率,细胞表型和基因表达.
- 使用了批量和单细胞RNA测序和ATAC测序.
- 评估了宫外hTERT表达的影响.
主要成果:
- 矩阵软化减少了WI-38细胞的增殖,并缩短了它们的增殖寿命.
- 软基质诱导了独特的细胞表型和独特的G1转录状态,其特征是AP-1程序.
- 宫外hTERT表达减轻或消除了基质刚性的对增殖和衰老的影响.
- 在软基质上的AP-1转录因子程序在hTERT表达细胞中没有观察到.
结论:
- 机械环境显著改变WI-38细胞的增殖寿命,并影响导致生长停止的途径.
- 基质刚性可以决定独特的细胞反应,包括特定的转录程序,这有助于衰老.
- 通过hTERT,端粒酶活性可以覆盖机械线索对细胞衰老和增殖的影响.
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