Introduction: Human dental pulp stem cells (DPSCs) are pivotal in tissue engineering and cell-based therapies due to their significant differentiation potential and accessibility. A major challenge in in vitro cell expansion is their replicative senescence, which impacts their regeneration and differentiation capabilities. While genetic factors influence these processes, epigenetic regulations such as Alu methylation also play crucial roles. Changes in Alu methylation have been associated with human aging and age-related diseases, contributing to cellular dysfunction and stem cell senescence. Despite this, the implications of Alu methylation alterations in stem cell senescence remain underexplored. This study focuses on examining Alu methylation during the replicative senescence of DPSCs.
Methods: The methylation status of Alu elements in serially passaged, long-term cultured human DPSCs was assessed using combined bisulfite restriction analysis. Morphological changes and indicators of replicative senescence were also evaluated. DPSCs were divided into three passage groups for analysis: early, middle, and late. Methylation levels across these groups were compared to identify trends correlating with passage number.
Results: Significant morphological changes and markers of replicative senescence were observed predominantly in the late-passage DPSCs. These cells exhibited notably lower levels of Alu methylation and higher proportions of hypomethylated Alu CpG sites compared to those in early passages.
Conclusion: The study confirmed that alterations in Alu methylation are evident in the replicative senescence of human DPSCs, suggesting that epigenetic modifications could influence the aging process of these cells and potentially impact their therapeutic efficacy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.tice.2024.102512 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
An appropriate DNA input for bisulfite conversion reveals LINE-1 and Alu hypermethylation in tissues and circulating cell-free DNA from cancers.
PLoS One
January 2025
Faculty of Biology, VNU University of Science, Vietnam National University, Hanoi, Vietnam.
The autonomous and active Long-Interspersed Element-1 (LINE-1, L1) and the non-autonomous Alu retrotransposon elements, contributing to 30% of the human genome, are the most abundant repeated sequences. With more than 90% of their sequences being methylated in normal cells, these elements undeniably contribute to the global DNA methylation level and constitute a major part of circulating-cell-free DNA (cfDNA). So far, the hypomethylation status of LINE-1 and Alu in cellular and extracellular DNA has long been considered a prevailing hallmark of ageing-related diseases and cancer.
View Article and Find Full Text PDFCan Global DNA Methylation Be Influenced by Polymorphisms in Genes Involved in Epigenetic Mechanisms? A Review.
Genes (Basel)
November 2024
Department of Celular Biology, Federal University of Paraná-UFPR, Curitiba 80060-000, PR, Brazil.
Background: Global methylation refers to the total methylation in the DNA and can also be inferred from the Line 1 and Alu regions, as these repeats are very abundant in the genome. The main function of DNA methylation is to control gene expression and is associated with both normal and pathological mechanisms. DNA methylation depends on enzymes that generate the methyl radical (e.
View Article and Find Full Text PDFExtensive epigenomic dysregulation is a hallmark of homologous recombination deficiency in triple-negative breast cancer.
Int J Cancer
December 2024
Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College, One Medical Center Drive, Lebanon, New Hampshire, USA.
Article Synopsis
- Triple-negative breast cancer (TNBC) is a highly aggressive subtype with varied characteristics, limited treatment choices, and poor clinical outcomes, particularly when associated with homologous recombination deficiency (HRD).
- The study analyzed TNBC tumors from two groups (n=32 and n=58), revealing significant differences in genome-wide copy number and methylation alterations linked to HRD, including lower methylation in specific genomic regions.
- Findings indicate that HRD in TNBC is associated with key biological pathways, and using machine learning can aid in classifying tumors based on HRD and methylation patterns, offering potential for improved treatment strategies.
Acteoside alleviates salsolinol-induced Parkinson's disease by inhibiting ferroptosis via activating Nrf2/SLC7A11/GPX4 pathway.
Exp Neurol
December 2024
Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing 100049, China. Electronic address:
Article Synopsis
- Salsolinol (SAL) is a neurotoxin linked to the development of Parkinson's disease (PD) by causing damage to dopaminergic neurons, and its mechanisms of toxicity involve inducing ferroptosis.
- The study utilized RNA sequencing and biochemical analysis to show that SAL decreases the levels of proteins SLC7A11 and GPX4, leading to ferroptosis in neuroblastoma cells, which can be reversed by ferroptosis inhibitors.
- Acteoside, a neuroprotective compound, counteracts SAL-induced neurotoxicity by enhancing SLC7A11 and GPX4 levels through activation of the Nrf2 pathway, suggesting a potential therapeutic strategy for PD by targeting ferroptosis.
Altered Methylation Levels in LINE-1 in Dental Pulp Stem Cell-Derived Osteoblasts.
Int Dent J
October 2024
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. Electronic address:
Objectives: Long interspersed nuclear element-1 (LINE-1) and Alu elements are major targets of methylation, an epigenetic mechanism that is associated with several biological processes. Alterations of methylation of LINE-1 and Alu have been reported in cancers, diseases, and ageing. However, these alterations have not been studied in osteogenic differentiation of dental pulp stem cells (DPSCs), which are a promising source of tissue regeneration.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!