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Telomerase Prevents Emphysema in Old Mice by Sustaining Subpopulations of Endothelial and AT2 Cells
bioRxiv - Molecular Biology Pub Date : 2021-01-30 , DOI: 10.1101/2021.01.07.425708
Marielle BREAU , Christelle CAYROU , Dmitri CHURIKOV , Charles FOUILLADE , Sandra CURRAS ALONSO , Serge BAUWENS , Frederic JOURQUIN , Laura BRAUD , Frederic FIORE , Remy CATELLANO , Emmanuelle JOSSELIN , Carlota SANCHEZ-FERRER , Giovanna GIOVINAZZO , Eric GILSON , Ignacio FLORES , Arturo LONDONO-VALLEJO , Serge ADNOT , Vincent GELI

Accumulation of senescent cells has been causally linked to the development of age-related pathologies. Here, we characterized a new mouse model (p21+/Tert) whose telomerase (TERT) is expressed from the p21 promoter that can be activated in response to telomere dysfunction. Lung parenchyma from p21+/Tert old mice accumulated fewer senescent cells with age and this correlated with a reduction in age-related alveolar space enlargement, a feature of pulmonary emphysema. This protection against emphysema depends on TERT catalytic activity and is associated with increased proliferation of pulmonary endothelial cells (EC) and capillary density. Single-cell RNA sequencing of lung cells revealed that TERT expression was associated with the enrichment of ECs expressing genes involved in vessel regeneration and in AT2 cells overexpressing S/G2M markers. These findings indicate that p21-promoter-dependent expression of catalytically active telomerase prevents emphysema by sustaining the proliferation of subclasses of EC and AT2 cells.

中文翻译:

端粒酶通过维持内皮细胞和AT2细胞亚群来预防老年小鼠的肺气肿

衰老细胞的积累与年龄相关疾病的发展有因果关系。在这里,我们表征了一种新的小鼠模型(p21 + / Tert),其端粒酶(TERT)从p21启动子表达,该启动子可以响应端粒功能障碍而被激活。p21 + / Tert老年小鼠的肺实质随着年龄的增长而积累的衰老细胞减少,这与年龄相关的肺泡空间增大(肺气肿的特征)减少有关。这种针对肺气肿的保护作用取决于TERT的催化活性,并与肺内皮细胞(EC)的增殖和毛细血管密度增加有关。肺细胞的单细胞RNA测序显示,TERT的表达与参与血管再生和过表达S / G2M标记的AT2细胞中EC表达基因的富集有关。
更新日期:2021-01-31
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