Surfaceome analysis of extracellular vesicles from senescent cells uncovers uptake repressor DPP4
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ABSTRACT:
PROVIDER: PRJNA889766 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21875900_1.fastq.gz | Fastqsanger.gz | |||
| SRR21875900_2.fastq.gz | Fastqsanger.gz | |||
| SRR21875901_1.fastq.gz | Fastqsanger.gz | |||
| SRR21875901_2.fastq.gz | Fastqsanger.gz | |||
| SRR21875902_1.fastq.gz | Fastqsanger.gz |
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Project description:Senescent cells are beneficial for repairing acute tissue damage, but they are harmful when they accumulate in tissues, as occurs with advancing age. Senescence-associated extracellular vesicles (S-EVs) can mediate cell-to-cell communication and export intracellular content to the microenvironment of aging tissues. Here, we studied the uptake of EVs from senescent cells (S-EVs) relative to proliferating cells (P-EVs). Interestingly, P-EVs were readily taken up by other proliferating cells (fibroblasts and cervical cancer cells) while S-EVs were not; by contrast, macrophages selectively engulfed all EVs (P-EVs, S-EVs). We thus investigated the surface proteome (surfaceome) of P-EVs relative to S-EVs derived from cells that had reached senescence via replicative exhaustion, exposure to ionizing radiation, or treatment with etoposide. We discovered that relative to P-EVs, S-EVs from all senescence models were enriched in proteins DPP4, ANXA1, ANXA6, S10AB, AT1A1, and EPHB2. Among them, DPP4 was found to dictate selective uptake by proliferating cells, as ectopic overexpression of DPP4 in HeLa cells rendered DPP-expressing EVs that were no longer taken up by other proliferating cells. We propose that DPP4 on the surface of S-EVs makes these EVs refractory to internalization by proliferating cells, advancing our knowledge of the impact of senescent cells in aging-associated processes.
2025-04-14 | GSE215322 | GEO
Project description:Senescent cells are beneficial for repairing acute tissue damage but are harmful when they accumulate in tissues, as occurs with advancing age. Senescence-associated extracellular vesicles (S-EVs) can mediate cell-to-cell communication and export intracellular content to the microenvironment of aging tissues. Here, we studied the uptake of EVs from senescent cells (S-EVs) relative to proliferating cells (P-EVs). Interestingly, P-EVs were readily taken up by other proliferating cells (fibroblasts and cervical cancer cells) while S-EVs were not; by contrast, macrophages selectively engulfed all EVs (P-EVs, S-EVs). We thus investigated the surface proteome (surfaceome) of P-EVs relative to S-EVs derived from cells that had reached senescence via replicative exhaustion, exposure to ionizing radiation, or treatment with etoposide. We discovered that relative to P-EVs, S-EVs from all senescence models were enriched in proteins DPP4, ANXA1, ANXA6, S10AB, AT1A1, and EPHB2. Among them, DPP4 was found to dictate selective uptake by proliferating cells, as ectopic overexpression of DPP4 in HeLa cells rendered DPP-expressing EVs that were no longer taken up by other proliferating cells. We propose that DPP4 on the surface of S-EVs makes these EVs refractory to internalization by proliferating cells, advancing our knowledge of the impact of senescent cells in aging-associated processes.
2022-10-09 | MSV000090503 | MassIVE
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2015-11-24 | E-GEOD-75328 | biostudies-arrayexpress
Project description:We performed scRNA sequencing to understand the composition and differential gene expression changes in aortic cells from LDLR-/- mice fed a normal diet (ND), high-fat diet (HFD), or HFD + DPP4i. We combined this technique with CITE-sequencing to measure the cell surface protein expression (DPP4) and transcriptomic changes associated with our experimental conditions as well as changes associated with DPP4 cell surface expression in all aortic cells.
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Project description:In hypoxic pulmonary hypertension (PH), pulmonary vascular remodeling is characterized by the emergence of activated adventitial fibroblasts, leading to medial smooth muscle hyperplasia. Previous studies have suggested that CD26/dipeptidyl peptidase-4 (DPP4) plays a crucial role in the pathobiological processes in lung diseases. However, its role in pulmonary fibroblasts in hy-poxic PH remains unknown. Therefore, we aimed to clarify the mechanistic role of CD26/DPP4 in lung fibroblasts in hypoxic PH. Dpp4 knockout (Dpp4 KO) and wild-type (WT) mice were exposed to hypoxia for 4 weeks. The degree of PH severity and medial wall thickness was augmented in Dpp4 KO mice compared with that in WT mice, suggesting that CD26/DPP4 plays a suppressive role in the development of hypoxic PH. Transcriptome analysis of human lung fibroblasts cultured under hypoxic conditions revealed that TGFB2, TGFB3, and TGFA were all upregulated as differentially expressed genes after DPP4 knockdown with small interfering RNA treatment. These results suggest that CD26/DPP4 plays a suppressive role in TGFβ signal-regulated fibroblast ac-tivation under hypoxic conditions. Therefore, CD26/DPP4 may be a potential therapeutic target in patients with PH associated with chronic hypoxia.
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Project description:We report here the overexpression of DPP4 in C28/I2 chondrocyte cells to investigate the changes induced by elevated levels of this gene. DPP4 is known as a marker of cellular senescence, yet its regulatory mechanisms remain unclear. In this study, we utilized the C28/I2 cell line to overexpress DPP4 and analyzed the resultant effects on gene expression and cellular behavior. Our findings reveal that DPP4 overexpression influences several pathways associated with chondrocyte function and senescence. Specifically, we observed alterations in pathways related to extracellular matrix organization, inflammatory response, and cellular aging. These results suggest that DPP4 plays a significant role in the modulation of chondrocyte senescence and may provide new insights into the mechanisms of cellular aging. Taken together, our data provide a molecular framework for understanding how DPP4 overexpression impacts chondrocyte physiology and offers potential targets for therapeutic intervention in age-related cartilage diseases.
2025-02-19 | GSE273261 | GEO
Project description:To examine the effects of DPP4 overexpression and its modulation by 4,5-Dicaffeoylquinic acid on chondrocytes, we established C28/I2 cell lines with DPP4 overexpression (DPP4OE), control empty vector (OENC), and DPP4OE treated with 4,5-Dicaffeoylquinic acid. Gene expression profiling analysis was performed using RNA sequencing (RNA-seq) with biological replicates to investigate the global transcriptomic changes associated with these conditions.
2025-02-19 | GSE273447 | GEO
Project description:Purpose: Next-generation sequencing (NGS) on senescent primary endothelial cells. The goals of this study was to compare NGS-derived transcriptome profiling (RNA-seq) of DPP4+ primary and secondary senescent endothelial cells isolated from multiple donors. Methods: Gene expression profile of DPP4+ isolated primary and secondary senescent endothelial cells were generated by deep sequencing, in triplicate, using Illumina Hiseq4000. After investigating the quality of the raw data, sequence reads were trimmed to remove possible adapter sequences and nucleotides with poor quality using Trimmomatic v.0.36. The trimmed reads were mapped to the reference genome available on ENSEMBL using the STAR aligner v.2.5.2b. BAM files were generated as a result of this step. Unique gene hit counts were calculated by using feature Counts from the Subread package v.1.5.2. Only unique reads that fell within exon regions were counted. Results: After extraction of gene hit counts, the gene hit counts table was used for downstream differential expression analysis. Using DESeq2, a comparison of gene expression between the groups of samples was performed. The Wald test was used to generate p-values and Log2 fold changes. Genes with adjusted p-values < 0.05 and absolute log2 fold changes > 1 were called as differentially expressed genes for each comparison. Conclusions: Our study represents the first detailed analysis of primary and secondary senescent cells transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles of primary and secondary senescence. Our results show that primary and secondary senescent cells have distinct gene expression profile.
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Project description:Elevated circulating dipeptidyl-peptidase 4 (DPP4) is a biomarker for liver disease, but its involvement in gluconeogenesis and metabolic associated fatty liver disease (MAFLD) progression remains unclear. Here we identified that DPP4 in hepatocytes but not Tie2+ endothelial cells regulates the local bioactivity of incretin hormones and gluconeogenesis. However, the complete absence of DPP4 (Dpp4-/-) in aged mice with metabolic syndrome accelerates liver fibrosis without altering dyslipidemia and steatosis. Analysis of transcripts from the livers of Dpp4-/- mice displayed enrichment for inflammasome, p53, and senescence programs compared to littermate controls. High-fat high-cholesterol (HFHC)-feeding decreased Dpp4 expression in F4/80+ cells, with only minor changes in immune signaling.
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Project description:Monomethyl auristatin E (MMAE) is used as the cytotoxic payload for enfortumab vedotin (EV) in the treatment of locally advanced and metastatic bladder cancer (BC). However, the development of resistance to MMAE in BC is a therapeutic problem. To explore the mechanism of resistance to MMAE in BC, we established MMAE-resistant BC cells (MR-BCs). RNA sequencing analysis showed that the expression of dipeptidyl peptidase 4 (DPP4, also called CD26) increased significantly in MR-BCs compared with parental BC cells. Knock down of DPP4 expression using small interfering RNA inhibited the viability of MR-BCs. In addition, the DPP4 inhibitor sitagliptin suppressed the proliferation, migration, and invasion of BC cells, and cotreatment with MMAE effectively induced cell apoptosis, arrested cells in the G2M phase of the cell cycle, increased reactive oxygen species production by inhibiting the AKT pathway, and significantly inhibited the in vivo growth of MMAE-resistant cells. This study provides insights into the use of DPP4 inhibitors as a treatment strategy for MMAE-resistant BC.
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