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Schematic representation of histone methylation and demethylation. DNA twines on histone proteins, including two dimers, H3/H4 and H2A/H2B, all of which compose a globular histone octamer and form the basic units of chromatin as nucleosomes. Histone methylation mainly occurs at arginine and lysine residues of the tail in H3/4 and is mediated by methyltransferases and histone demethylation is regulated by demethylases. Histone methylation can affect the spatial structure of chromatin by affecting the structure of nucleosomes and thus regulating the expression activity of genes. The nucleosome structure usually becomes crowded by adding methyl group (Me) from arginine and lysine residues of the tail, which making it difficult for gene segments to be transcribed, so gene expression is silenced. In contrast, the demethylation of histone usually could induce the open histone structure by removing methyl group (Me) from arginine and lysine residues of the tail, which expose the transcription factor binding sites and regulates the transcriptional activation of genes.
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Dental mesenchymal stem cells (DMSCs) are crucial in tooth development and periodontal health, and their multipotential differentiation and self-renewal ability play a critical role in tissue engineering and regenerative medicine. Methylation modifications could promote the appropriate biological behavior by postsynthetic modification of DNA or pro...
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Adult stem cells maintaining tissue homeostasis and regeneration are tightly regulated by their specific microenvironments or stem cell niches. The dysfunction of niche components may alter the activity of stem cells and ultimately lead to intractable chronic or acute disorders. To overcome this dysfunction, niche-targeting regenerative medicine tr...
Citations
... Other transcriptional factors, such as CCAAT/enhancer-binding proteins (C/EBPs) and adiponectin (ADIPOQ), also play crucial roles in adipogenesis within PDLSCs [6]. It has been reported that both changes in transcriptional activity and cell differentiation involve chromatin reconfiguration mediated by epigenetic mechanisms, including DNA methylation, microRNAs, and post-translational modifications (PTMs) of histones [7][8][9][10]. ...
... The differentiation process of DSCs is significantly influenced by a range of regulatory factors, with previous studies primarily focusing on genetic, epigenetic, and molecular aspects [17][18][19]. Recently, the role of autophagy in DSC differentiation has emerged as a research hotspot. ...
Dental stem cells (DSCs) have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune response. These properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative medicine. While many regulatory factors determine the differentiation trajectory of DSCs, prior research has predominantly been based on genetic, epigenetic, and molecular aspects. Recent evidence suggests that DSC differentiation can also be influenced by autophagy, a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress conditions. This comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC differentiation. To achieve this goal, we dissect the intricacies of autophagy and its mechanisms. Subsequently, we elucidate its pivotal roles in impacting DSC differentiation, including osteo/odontogenic, neurogenic, and angiogenic trajectories. Furthermore, we reveal the regulatory factors that govern autophagy in DSC lineage commitment, including scaffold materials, pharmaceutical cues, and the extrinsic milieu. The implications of this review are far-reaching, underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine.
... It can be projected that in the future, the integration of these sub-fields will likely continue to drive the advances in personalized medicine, with gene therapy and epigenetic modifications being used to target specific diseases and individual patients [10,12]. Additionally, ongoing research in DNA replication and repair mechanisms will likely lead to the development of new therapies and drugs for cancer and other genetic diseases [13][14][15]. Henceforth, it is worth mentioning that while there are still many unknowns and complexities to be navigated, the potential benefits of this research and innovation area are immense and will undoubtedly play a critical role in shaping the future of medicine and biotechnology [1, 3, 6, 10]. ...
... Today, DNA replication, epigenetics, and gene therapy are at the forefront of cutting-edge research and innovation with many recent advances and promising developments [12,14,15]. In laboratories, researchers are working to unravel the complexities of DNA replication, with a particular focus on the mechanisms of initiation and termination, functional cross-talk with the genome, and DNA recombination and repair, for example. ...
... Further, new analytical methods, such as single-cell sequencing and CRISPR-based gene editing, are also being developed to enhance our understanding of DNA replication and its role in human health and disease. In the sub-field of epigenetics, recent studies have revealed the potential of epigenetic modifications, such as DNA methylation, histone modification, and non-coding RNA molecules, to be used as therapeutic targets for a range of diseases [15]. For example, recent research has shown that targeting epigenetic modifiers can reverse drug Introductory Chapter: Unraveling the Complexities of DNA Replication, Epigenetics, and Gene… DOI: http://dx.doi.org ...
Cancer onset and progression are known to be regulated by genetic and epigenetic events, including RNA modifications (a.k.a. epitranscriptomics). So far, more than 150 chemical modifications have been described in all RNA subtypes, including messenger, ribosomal, and transfer RNAs. RNA modifications and their regulators are known to be implicated in all steps of post-transcriptional regulation. The dysregulation of this complex yet delicate balance can contribute to disease evolution, particularly in the context of carcinogenesis, where cells are subjected to various stresses. We sought to discover RNA modifications involved in cancer cell adaptation to inhospitable environments, a peculiar feature of cancer stem cells (CSCs). We were particularly interested in the RNA marks that help the adaptation of cancer cells to suspension culture, which is often used as a surrogate to evaluate the tumorigenic potential. For this purpose, we designed an experimental pipeline consisting of four steps: (1) cell culture in different growth conditions to favor CSC survival; (2) simultaneous RNA subtype (mRNA, rRNA, tRNA) enrichment and RNA hydrolysis; (3) the multiplex analysis of nucleosides by LC-MS/MS followed by statistical/bioinformatic analysis; and (4) the functional validation of identified RNA marks. This study demonstrates that the RNA modification landscape evolves along with the cancer cell phenotype under growth constraints. Remarkably, we discovered a short epitranscriptomic signature, conserved across colorectal cancer cell lines and associated with enrichment in CSCs. Functional tests confirmed the importance of selected marks in the process of adaptation to suspension culture, confirming the validity of our approach and opening up interesting prospects in the field.
