scholarly journals Epigenetic Regulation of Dental Pulp Stem Cell Fate

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Dan Zhou ◽  
Lu Gan ◽  
Yiran Peng ◽  
Yachuan Zhou ◽  
Xin Zhou ◽  
...  

Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs, affects gene expression without modifying the primary DNA sequence and modulates cell fate. Mesenchymal stem cells derived from dental pulp, also called dental pulp stem cells (DPSCs), exhibit multipotent differentiation capacity and can promote various biological processes, including odontogenesis, osteogenesis, angiogenesis, myogenesis, and chondrogenesis. Over the past decades, increased attention has been attracted by the use of DPSCs in the field of regenerative medicine. According to a series of studies, epigenetic regulation is essential for DPSCs to differentiate into specialized cells. In this review, we summarize the mechanisms involved in the epigenetic regulation of the fate of DPSCs.

2014 ◽  
Vol 40 (4) ◽  
pp. S33-S40 ◽  
Author(s):  
Evandro Piva ◽  
Adriana F. Silva ◽  
Jacques E. Nör

2017 ◽  
Vol 2017 ◽  
pp. 1-13
Author(s):  
Fuquan Chen ◽  
Jiaojiao Ji ◽  
Jian Shen ◽  
Xinyi Lu

Most of the human genome can be transcribed into RNAs, but only a minority of these regions produce protein-coding mRNAs whereas the remaining regions are transcribed into noncoding RNAs. Long noncoding RNAs (lncRNAs) were known for their influential regulatory roles in multiple biological processes such as imprinting, dosage compensation, transcriptional regulation, and splicing. The physiological functions of protein-coding genes have been extensively characterized through genome editing in pluripotent stem cells (PSCs) in the past 30 years; however, the study of lncRNAs with genome editing technologies only came into attentions in recent years. Here, we summarize recent advancements in dissecting the roles of lncRNAs with genome editing technologies in PSCs and highlight potential genome editing tools useful for examining the functions of lncRNAs in PSCs.


2021 ◽  
Author(s):  
min xiao ◽  
Bo Yao ◽  
Xiaohan Mei ◽  
yu bai ◽  
Jueyu Wang ◽  
...  

Abstract Background SDF-1α cotreatment was shown to have synergistic effects on BMP-2-induced odontogenic differentiation of human apical dental papillary stem cells (SCAP) both in vitro and in vivo. Long noncoding RNAs (lncRNAs) have an important role in the odontogenic differentiation of dental pulp stem cells (DPSCs). Methods We examined the altered expression of lncRNAs in SDF-1α-induced odontogenic differentiation of DPSCs by lncRNA microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses. Alterations in lncRNA expression during odontogenic differentiation of DPSCs were identified. Moreover, bioinformatic analysis [Gene Ontology (GO) analysis and coding-noncoding gene coexpression (CNC) analysis] was conducted to predict the interactions of lncRNAs and identify core regulatory factors in SDF-1α-induced odontogenic differentiation of DPSCs. Results The microarray analysis identified 206 differentially expressed lncRNAs (134 lncRNAs with upregulated expression and 72 with downregulated expression) at 7 days post‑treatment. The data demonstrated that one lncRNA, AC080037.1, regulates SDF-1α-induced odontogenic differentiation of DPSCs. Our data showed that lncRNA AC080037.1 siRNA suppresses DPSCs migration and the expression of Rho GTPase induced by SDF-1α. Moreover, AC080037.1 knockdown significantly affected SDF-1α- and BMP-2-induced mineralized nodule formation and strongly suppressed Runt-related factor-2 (RUNX-2), DMP-1 and DSPP expression in DPSCs. Conclusions Our


Blood ◽  
2021 ◽  
Author(s):  
Dirk Loeffler ◽  
Florin Schneiter ◽  
Weijia Wang ◽  
Arne Wehling ◽  
Tobias Kull ◽  
...  

Understanding human hematopoietic stem cell fate control is important for their improved therapeutic manipulation. Asymmetric cell division, the asymmetric inheritance of factors during division instructing future daughter cell fates, was recently described in mouse blood stem cells. In human blood stem cells, the possible existence of asymmetric cell division remained unclear due to technical challenges in its direct observation. Here, we use long-term quantitative single-cell imaging to show that lysosomes and active mitochondria are asymmetrically inherited in human blood stem cells and that their inheritance is a coordinated, non-random process. Furthermore, multiple additional organelles, including autophagosomes, mitophagosomes, autolysosomes and recycling endosomes show preferential asymmetric co-segregation with lysosomes. Importantly, asymmetric lysosomal inheritance predicts future asymmetric daughter cell cycle length, differentiation and stem cell marker expression, while asymmetric inheritance of active mitochondria correlates with daughter metabolic activity. Hence, human hematopoietic stem cell fates are regulated by asymmetric cell division, with both mechanistic evolutionary conservation and differences to the mouse system.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Fuchun Fang ◽  
Kaiying Zhang ◽  
Zhao Chen ◽  
Buling Wu

Abstract Odontoblasts are cells that contribute to the formation of the dental pulp complex. The differentiation of dental tissue-derived mesenchymal stem cells into odontoblasts comprises many factors and signaling pathways. Noncoding RNAs (ncRNAs), comprising a substantial part of poly-A tail mature RNAs, are considered “transcriptional noise.” Emerging evidence has shown that ncRNAs have key functions in the differentiation of mesenchymal stem cells. In this review, we discussed two major types of ncRNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), in terms of their role in the odontogenic differentiation of dental tissue-derived stem cells. Recent findings have demonstrated important functions for miRNAs and lncRNAs in odontogenic differentiation. It is expected that ncRNAs will become promising therapeutic targets for dentin regeneration based on stem cells.


2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Pengfei Ji ◽  
Xia Wang ◽  
Nina Xie ◽  
Yujing Li

Vast emerging evidences are linking the base modifications and determination of stem cell fate such as proliferation and differentiation. Among the base modification markers extensively studied, 5-methylcytosine (5-mC) and its oxidative derivatives (5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC)) dynamically occur in DNA and RNA and have been acknowledged as important epigenetic markers involved in regulation of cellular biological processes. N6-Methyladenosine modification in DNA (m6dA), mRNA (m6A), tRNA, and other noncoding RNAs has been defined as another important epigenetic and epitranscriptomic marker in eukaryotes in recent years. The mRNA m6A modification has been characterized biochemically, molecularly, and phenotypically, including elucidation of its methyltransferase complexes (m6A writer), demethylases (m6A eraser), and direct interaction proteins (readers), while limited information on the DNA m6dA is available. The levels and the landscapes of m6A in the epitranscriptomes and epigenomes are precisely and dynamically regulated by the fine-tuned coordination of the writers and erasers in accordance with stages of the growth, development, and reproduction as naturally programmed during the lifespan. Additionally, progress has been made in appreciation of the link between aberrant m6A modification in stem cells and diseases, like cancers and neurodegenerative disorders. These achievements are inspiring scientists to further uncover the epigenetic mechanisms for stem cell development and to dissect pathogenesis of the multiple diseases conferred by development aberration of the stem cells. This review article will highlight the research advances in the role of m6A methylation modifications of DNA and RNA in the regulation of stem cell and genesis of the closely related disorders. Additionally, this article will also address the research directions in the future.


2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Fei Xing ◽  
Lang Li ◽  
Changchun Zhou ◽  
Cheng Long ◽  
Lina Wu ◽  
...  

It is well known that stem cells reside within tissue engineering functional microenvironments that physically localize them and direct their stem cell fate. Recent efforts in the development of more complex and engineered scaffold technologies, together with new understanding of stem cell behavior in vitro, have provided a new impetus to study regulation and directing stem cell fate. A variety of tissue engineering technologies have been developed to regulate the fate of stem cells. Traditional methods to change the fate of stem cells are adding growth factors or some signaling pathways. In recent years, many studies have revealed that the geometrical microenvironment played an essential role in regulating the fate of stem cells, and the physical factors of scaffolds including mechanical properties, pore sizes, porosity, surface stiffness, three-dimensional structures, and mechanical stimulation may affect the fate of stem cells. Chemical factors such as cell-adhesive ligands and exogenous growth factors would also regulate the fate of stem cells. Understanding how these physical and chemical cues affect the fate of stem cells is essential for building more complex and controlled scaffolds for directing stem cell fate.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vitor C. M. Neves ◽  
Val Yianni ◽  
Paul T. Sharpe

AbstractThe interaction between immune cells and stem cells is important during tissue repair. Macrophages have been described as being crucial for limb regeneration and in certain circumstances have been shown to affect stem cell differentiation in vivo. Dentine is susceptible to damage as a result of caries, pulp infection and inflammation all of which are major problems in tooth restoration. Characterising the interplay between immune cells and stem cells is crucial to understand how to improve natural repair mechanisms. In this study, we used an in vivo damage model, associated with a macrophage and neutrophil depletion model to investigate the role of immune cells in reparative dentine formation. In addition, we investigated the effect of elevating the Wnt/β-catenin pathway to understand how this might regulate macrophages and impact upon Wnt receiving pulp stem cells during repair. Our results show that macrophages are required for dental pulp stem cell activation and appropriate reparative dentine formation. In addition, pharmacological stimulation of the Wnt/β-catenin pathway via GSK-3β inhibitor small molecules polarises macrophages to an anti-inflammatory state faster than inert calcium silicate-based materials thereby accelerating stem cell activation and repair. Wnt/β-catenin signalling thus has a dual role in promoting reparative dentine formation by activating pulp stem cells and promoting an anti-inflammatory macrophage response.


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