...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nucleus >Soft substrates normalize nuclear morphology and prevent nuclear rupture in fibroblasts from a laminopathy patient with compound heterozygous LMNA mutations
【24h】

Soft substrates normalize nuclear morphology and prevent nuclear rupture in fibroblasts from a laminopathy patient with compound heterozygous LMNA mutations

机译：软底物可使核形态正常化，并防止具有复合杂合LMNA突变的椎板病患者的成纤维细胞中的核破裂。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Laminopathies, mainly caused by mutations in the LMNA gene, are a group of inherited diseases with a highly variable penetrance; i.e., the disease spectrum in persons with identical LMNA mutations range from symptom-free conditions to severe cardiomyopathy and progeria, leading to early death. LMNA mutations cause nuclear abnormalities and cellular fragility in response to cellular mechanical stress, but the genotype/phenotype correlations in these diseases remain unclear. Consequently, tools such as mutation analysis are not adequate for predicting the course of the disease. ? Here, we employ growth substrate stiffness to probe nuclear fragility in cultured dermal fibroblasts from a laminopathy patient with compound progeroid syndrome. We show that culturing of these cells on substrates with stiffness higher than 10 kPa results in malformations and even rupture of the nuclei, while culture on a soft substrate (3 kPa) protects the nuclei from morphological alterations and ruptures. No malformations were seen in healthy control cells at any substrate stiffness. In addition, analysis of the actin cytoskeleton organization in this laminopathy cells demonstrates that the onset of nuclear abnormalities correlates to an increase in cytoskeletal tension. Together, these data indicate that culturing of these LMNA mutated cells on substrates with a range of different stiffnesses can be used to probe the degree of nuclear fragility. This assay may be useful in predicting patient-specific phenotypic development and in investigations on the underlying mechanisms of nuclear and cellular fragility in laminopathies.
机译：主要由LMNA基因突变引起的椎病是一组遗传性疾病，其外在性很高。即，具有相同LMNA突变的人的疾病谱范围从无症状到严重的心肌病和早衰，导致早期死亡。 LMNA突变会响应细胞机械应力而引起核异常和细胞脆性，但这些疾病的基因型/表型相关性仍不清楚。因此，诸如突变分析之类的工具不足以预测疾病的进程。 ？在这里，我们采用生长基质刚度来检测来自患有复合性早老综合征的椎板病患者的培养真皮成纤维细胞中的核脆性。我们表明，在刚度高于10 kPa的底物上培养这些细胞会导致畸形，甚至使核破裂，而在柔软的底物（3 kPa）上进行培养可保护核免于形态变化和破裂。在健康的对照细胞中，在任何底物硬度下均未见畸形。另外，对该椎板病细胞中肌动蛋白细胞骨架组织的分析表明，核异常的发生与细胞骨架张力的增加有关。总之，这些数据表明这些LMNA突变细胞在具有不同刚度范围的底物上的培养可用于探测核脆性的程度。该测定法可用于预测患者特异的表型发展，并用于研究椎间盘突出症的核和细胞脆性的潜在机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号