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Series GSE228491 Query DataSets for GSE228491
Status Public on Apr 30, 2023
Title Endothelial cell senescence exacerbates pulmonary hypertension by inducing juxtacrine Notch signaling in smooth muscle cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a progressive increase in pulmonary artery pressure caused by pathological pulmonary artery remodeling. Here, we show that endothelial cell (EC) senescence plays a negative role in pulmonary hypertension via juxtacrine interaction with smooth muscle cells (SMCs). By using EC-specific progeroid mice that we recently generated, we discovered that EC progeria deteriorated vascular remodeling in the lungs, and exacerbated pulmonary hypertension in mice exposed to chronic hypoxia. Mechanistically, senescent ECs overexpressed Notch ligands, which resulted in increased Notch signaling and activated proliferation and migration capacities in neighboring SMCs. Pharmacological inhibition of Notch signaling reduced the effects of senescent ECs on SMCs functions in vitro, and improved the worsened pulmonary hypertension in EC-specific progeroid mice in vivo. Our findings show that EC senescence is a critical disease-modifying factor in PAH and that EC-mediated Notch signaling is a pharmacotherapeutic target for the treatment of PAH, particularly in the elderly.
Overall design single nucleus RNA sequencing was used to profile mouse lung
Contributor(s) Ikeda K
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Submission date Mar 29, 2023
Last update date May 02, 2023
Contact name Tetsuro Kusaba
Organization name Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Department Department of Nephrology
Street address 465 Kajii-cho, Kamigyo-ku
City Kyoto
State/province Kyoto
ZIP/Postal code 6028566
Country Japan
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM7122676 wt, replicate 1, snRNAseq
GSM7122677 wt, replicate 2, snRNAseq
GSM7122678 tg, replicate 1, snRNAseq
BioProject PRJNA950045

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Supplementary file Size Download File type/resource
GSE228491_RAW.tar 1.4 Gb (http)(custom) TAR (of MTX, TSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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