Experiment Id | GSE239686 | Name | Genomic analysis of mice with endothelium-specific TERT knockout (RNA-Seq) |
Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
Source | GEO | Curation Date | 2024-08-09 |
description | Health of endothelial cells (EC) is fundamental for function of vital organs. There is evidence accumulating that senescence of EC is associated with aging-related diseases. However, it has not been established whether EC senescence underlies the pathophysiology of aging. Here, we report a mouse model of EC senescence. Inactivation of telomerase (TERT) expression sets the stage for aging and predisposes cells to replicative senescence. TERT maintains telomere length and has telomere-independent effects on cell transcriptome and physiology. We generated mice with TERT gene knock-out (KO) specifically in EC. We analyzed EC from adipose tissues (AT) and skeletal muscle cells from Tert-EC-KO and control mice raised on either chow or high-calorie diet (HCD) and subjected them to RNA sequencing (RNAseq). Single cell RNAseq data were also obtained for subcutaneous and visceral AT. Preliminary analysis of data deposited online indicates that TERT KO induces premature cell senescence and dysfunction. Moreover, HCD feeding exacerbates the effect of TERT loss. We conclude that the Tert-EC-KO mice are a useful model to study EC senescence and its effects on aging-associated organ dysfunction. Tie2e-cre; TERT+/+; mTmG (WT) and Tie2e-cre; TERTfl/fl; mTmG (TERT-EC-KO) 8 month-old female mice were fed chow (C) or HFD (H). Cells isolated from subcutaneous AT (SAT), intraperitoneal visceral AT (VAT), and gastrocnemius skeletal muscle (M) were subjected to FACS sorting to isolate mG+ (GFP+) cells for mRNA extraction. |