GEO series
PUS7-Mediated Pseudouridylation of TGFBI Drives Vascular Remodeling in Pulmonary Hypertension [BID-seq]
GSE335339
Homo sapiens
Other; Expression profiling by high throughput sequencing
20 samples
Submitted 2026/07/07
Platform GPL24676
Summary
Background: Pulmonary hypertension (PH) is a life-threatening cardiovascular disorder characterized by irreversible pulmonary vascular remodeling and poor prognosis. RNA pseudouridylation, the most evolutionarily conserved RNA epigenetic modification, and its catalytic enzyme pseudouridine synthase 7 (PUS7) remained uncharacterized in PH, representing a major gap in understanding the epigenetic pathogenesis of the disease. Methods: We generated the first single-base resolution pseudouridine (Ψ) landscape in lung tissues of PH patients using bisulfite-induced deletion sequencing (BID-seq). PUS7 expression was analyzed in hypoxic pulmonary artery endothelial cells (PAECs), the lung tissues of PH patients, and Su5416-hypoxia rodent model. The functional roles of PUS7 were investigated through genetic manipulation (PUS7-deficiency cells, AAV-mediated overexpression, endothelial cell-specific knockdown, and heterozygous knockout mice) and pharmacological inhibition using NSC107512. Results: BID-seq revealed global Ψ dysregulation in the PH patient lung tissues. Among PUS family members, PUS7 was the most markedly upregulated in these tissues and in the hypoxic PAECs. Both gene knockdown and pharmacological inhibition with NSC107512 ameliorated PH, whereas AAV-mediated PUS7 overexpression exacerbated disease progression. RNA immunoprecipitation sequencing and mutagenesis studies demonstrated that PUS7 bound to and catalyzed Ψ at position 688 of Transforming Growth Factor Beta Induced Protein (TGFBI) mRNA, thereby stabilizing TGFBI and activating Phosphatidylinositol 3 Kinase (PI3K)-Protein Kinase B (AKT) signaling pathway. Furthermore, hypoxia-inducible factor 2α (HIF-2α) directly bound the PUS7 promoter, estabilishing a HIF-2α/PUS7/TGFBI/PI3K-AKT positive feedback loop that drives PH pathogenesis. Conclusions: PUS7-mediated pseudouridylation serves as a novel epigenetic driver of PH via the HIF-2α/PUS7/TGFBI/PI3K-AKT axis, positioning PUS7 as a promising therapeutic target for this devastating disease.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE335339_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 20 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1477955 and SRA study SRP709196. Searching any of these in the dataset finder brings you back here.
Study design
20 conditions, each sampled once — no replicated groups
Read from 20 sample titles: 20 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9812183 Control1_Input
- GSM9812184 Control1_Treat
- GSM9812185 Control2_Input
- GSM9812186 Control2_Treat
- GSM9812187 Control3_Input
- GSM9812188 Control3_Treat
- GSM9812189 Control4_Input
- GSM9812190 Control4_Treat
- GSM9812191 PH1_Input
- GSM9812192 PH1_Treat
- GSM9812193 PH2_Input
- GSM9812194 PH2_Treat
- GSM9812195 PH3_Input
- GSM9812196 PH3_Treat
- GSM9812197 PH4_Input
- GSM9812198 PH4_Treat
- GSM9817110 Control5_Input
- GSM9817111 Control5_Treat
- GSM9817112 PH5_Input
- GSM9817113 PH5_Treat
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