Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hm...Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hmC） ten-eleven transtocation （TET） enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews （Tupaia belangeri chinensis）. The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.展开更多
Mesenchymal stem cells(MSCs)are a heterogeneous population that can be isolated from various tissues,including bone marrow,adipose tissue,umbilical cord blood,and craniofacial tissue.MSCs have attracted increasingly m...Mesenchymal stem cells(MSCs)are a heterogeneous population that can be isolated from various tissues,including bone marrow,adipose tissue,umbilical cord blood,and craniofacial tissue.MSCs have attracted increasingly more attention over the years due to their regenerative capacity and function in immunomodulation.The foundation of tissue regeneration is the potential of cells to differentiate into multiple cell lineages and give rise to multiple tissue types.In addition,the immunoregulatory function of MSCs has provided insights into therapeutic treatments for immune-mediated diseases.DNA methylation and demethylation are important epigenetic mechanisms that have been shown to modulate embryonic stem cell maintenance,proliferation,differentiation and apoptosis by activating or suppressing a number of genes.In most studies,DNA hypermethylation is associated with gene suppression,while hypomethylation or demethylation is associated with gene activation.The dynamic balance of DNA methylation and demethylation is required for normal mammalian development and inhibits the onset of abnormal phenotypes.However,the exact role of DNA methylation and demethylation in MSC-based tissue regeneration and immunomodulation requires further investigation.In this review,we discuss how DNA methylation and demethylation function in multi-lineage cell differentiation and immunomodulation of MSCs based on previously published work.Furthermore,we discuss the implications of the role of DNA methylation and demethylation in MSCs for the treatment of metabolic or immune-related diseases.展开更多
Recent evidence shows that increased oxidative stress and aging contribute to DNA damage in various cardiovascular diseases such as lipid disorders and atherosclerosis. In the present study, we used the comet assay to...Recent evidence shows that increased oxidative stress and aging contribute to DNA damage in various cardiovascular diseases such as lipid disorders and atherosclerosis. In the present study, we used the comet assay to evaluate the influ- ence of aging on DNA damage in whole blood cells from apolipoprotein E-deficient (apoE?/?) mice and compared the results to those found in cells from wild-type C57BL/6 (C57) mice. Using the alkaline comet assay and fluorescent ethidium bromide staining, DNA damage was analyzed in the peripheral whole blood (5 μL) cells that were isolated from either young (8-week-old) and elderly (72-week-old) apoE?/? mice or from age-matched C57 mice. The levels of total plasma cholesterol were approximately 6-fold higher in apoE?/? mice of both ages compared to C57 mice. Elderly apoE?/? mice showed significantly higher levels of DNA damage (19%) compared to elderly C57 mice (8%, p < 0.01) and young apoE?/? mice (10%, p < 0.01). The comet assay in whole blood cells is a suitable technique for the detection of DNA damage in the apoE?/? mouse;it is an easy, rapid, inexpensive and sensitive method. The novelty of this study is that DNA damage occurring in whole blood cells of this murine model requires the concurrence of aging and oxida- tive stress-related hypercholesterolemia.展开更多
Human dental pulp cells （hDPCs） possess the capacity to differentiate into odontoblast-like cells and generate reparative dentin in response to exogenous stimuli or injury. Ten-eleven translocation 1 （TET1） is a n...Human dental pulp cells （hDPCs） possess the capacity to differentiate into odontoblast-like cells and generate reparative dentin in response to exogenous stimuli or injury. Ten-eleven translocation 1 （TET1） is a novel DNA methyldioxygenase that plays an important role in the promotion of DNA demethylation and transcriptional regulation in several cell lines. However, the role of TET1 in the biological functions of hDPCs is unknown. To investigate the effect of TET1 on the proliferation and odontogenic differentiation potential of hDPCs, a recombinant shRNA lentiviral vector was used to knock down TET1 expression in hDPCs. Following TET1 knockdown, TET1 was significantly downregulated at both the mRNA and protein levels. Proliferation of the hDPCs was suppressed in the TET1 knockdown groups. Alkaline phosphatase activity, the formation of mineralized nodules, and the expression levels of DSPP and DMP1 were all reduced in the TETl-knockdown hDPCs undergoing odontogenic differentiation. Based on these results, we concluded that TET1 knockdown can prevent the proliferation and odontogenic differentiation of hDPCs, which suggests that TET1 may play an important role in dental pulp repair and regeneration.展开更多
BACKGROUND As the third most abundant element,aluminum is widespread in the environment.Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive ...BACKGROUND As the third most abundant element,aluminum is widespread in the environment.Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive function.AIM To study the effects of aluminum on epigenetic modification in neural stem cells and neurons.METHODS Neural stem cells were isolated from the forebrain of adult mice.Neurons were isolated from the hippocampi tissues of embryonic day 16-18 mice.AlCl3 at 100 and 200μmol/L was applied to stem cells and neurons.RESULTS Aluminum altered the differentiation of adult neural stem cells and caused apoptosis of newborn neurons while having no significant effects on the proliferation of neural stem cells.Aluminum application also significantly inhibited the dendritic development of hippocampal neurons.Mechanistically,aluminum exposure significantly affected the levels of DNA 5-hydroxy methylcytosine,5-methylcytosine,and N6-methyladenine in stem cells and neurons.CONCLUSION Our findings indicate that aluminum may regulate neuronal development by modulating DNA modifications.展开更多
基金supported by the Hundred-Talent Program of Chinese Academy of Sciences(Y4065411411100050210)to J.L.+3 种基金the National Natural Science Foundation of China(8147131391649119)to J.L.the National Natural Science Foundation of China(31260242 to)F.Lthe National Science and Technology Infrastructure Program(2014BAI01B01-04)to S.L.
文摘Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hmC） ten-eleven transtocation （TET） enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews （Tupaia belangeri chinensis）. The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.
基金Supported by Beijing Natural Science Foundation,No.7182182the Young Elite Scientist Sponsorship Program by Cast,No.YESS20170089+1 种基金the National Natural Science Foundation of China,No.81600865 and No.81970940the National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2018ZX10302207。
文摘Mesenchymal stem cells(MSCs)are a heterogeneous population that can be isolated from various tissues,including bone marrow,adipose tissue,umbilical cord blood,and craniofacial tissue.MSCs have attracted increasingly more attention over the years due to their regenerative capacity and function in immunomodulation.The foundation of tissue regeneration is the potential of cells to differentiate into multiple cell lineages and give rise to multiple tissue types.In addition,the immunoregulatory function of MSCs has provided insights into therapeutic treatments for immune-mediated diseases.DNA methylation and demethylation are important epigenetic mechanisms that have been shown to modulate embryonic stem cell maintenance,proliferation,differentiation and apoptosis by activating or suppressing a number of genes.In most studies,DNA hypermethylation is associated with gene suppression,while hypomethylation or demethylation is associated with gene activation.The dynamic balance of DNA methylation and demethylation is required for normal mammalian development and inhibits the onset of abnormal phenotypes.However,the exact role of DNA methylation and demethylation in MSC-based tissue regeneration and immunomodulation requires further investigation.In this review,we discuss how DNA methylation and demethylation function in multi-lineage cell differentiation and immunomodulation of MSCs based on previously published work.Furthermore,we discuss the implications of the role of DNA methylation and demethylation in MSCs for the treatment of metabolic or immune-related diseases.
文摘Recent evidence shows that increased oxidative stress and aging contribute to DNA damage in various cardiovascular diseases such as lipid disorders and atherosclerosis. In the present study, we used the comet assay to evaluate the influ- ence of aging on DNA damage in whole blood cells from apolipoprotein E-deficient (apoE?/?) mice and compared the results to those found in cells from wild-type C57BL/6 (C57) mice. Using the alkaline comet assay and fluorescent ethidium bromide staining, DNA damage was analyzed in the peripheral whole blood (5 μL) cells that were isolated from either young (8-week-old) and elderly (72-week-old) apoE?/? mice or from age-matched C57 mice. The levels of total plasma cholesterol were approximately 6-fold higher in apoE?/? mice of both ages compared to C57 mice. Elderly apoE?/? mice showed significantly higher levels of DNA damage (19%) compared to elderly C57 mice (8%, p < 0.01) and young apoE?/? mice (10%, p < 0.01). The comet assay in whole blood cells is a suitable technique for the detection of DNA damage in the apoE?/? mouse;it is an easy, rapid, inexpensive and sensitive method. The novelty of this study is that DNA damage occurring in whole blood cells of this murine model requires the concurrence of aging and oxida- tive stress-related hypercholesterolemia.
基金supported by the National Nature Science Foundation of China (grant no.81570971)
文摘Human dental pulp cells （hDPCs） possess the capacity to differentiate into odontoblast-like cells and generate reparative dentin in response to exogenous stimuli or injury. Ten-eleven translocation 1 （TET1） is a novel DNA methyldioxygenase that plays an important role in the promotion of DNA demethylation and transcriptional regulation in several cell lines. However, the role of TET1 in the biological functions of hDPCs is unknown. To investigate the effect of TET1 on the proliferation and odontogenic differentiation potential of hDPCs, a recombinant shRNA lentiviral vector was used to knock down TET1 expression in hDPCs. Following TET1 knockdown, TET1 was significantly downregulated at both the mRNA and protein levels. Proliferation of the hDPCs was suppressed in the TET1 knockdown groups. Alkaline phosphatase activity, the formation of mineralized nodules, and the expression levels of DSPP and DMP1 were all reduced in the TETl-knockdown hDPCs undergoing odontogenic differentiation. Based on these results, we concluded that TET1 knockdown can prevent the proliferation and odontogenic differentiation of hDPCs, which suggests that TET1 may play an important role in dental pulp repair and regeneration.
文摘BACKGROUND As the third most abundant element,aluminum is widespread in the environment.Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive function.AIM To study the effects of aluminum on epigenetic modification in neural stem cells and neurons.METHODS Neural stem cells were isolated from the forebrain of adult mice.Neurons were isolated from the hippocampi tissues of embryonic day 16-18 mice.AlCl3 at 100 and 200μmol/L was applied to stem cells and neurons.RESULTS Aluminum altered the differentiation of adult neural stem cells and caused apoptosis of newborn neurons while having no significant effects on the proliferation of neural stem cells.Aluminum application also significantly inhibited the dendritic development of hippocampal neurons.Mechanistically,aluminum exposure significantly affected the levels of DNA 5-hydroxy methylcytosine,5-methylcytosine,and N6-methyladenine in stem cells and neurons.CONCLUSION Our findings indicate that aluminum may regulate neuronal development by modulating DNA modifications.
