Browsing by Author "Chen, Yuanyuan"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Cell-Wide DNA De-Methylation and Re-Methylation of Purkinje Neurons in the Developing Cerebellum
    (Plos, 2016-09) Zhou, Feng C.; Resendiz, Marisol; Lo, Chiao-Ling; Chen, Yuanyuan; Department of Anatomy & Cell Biology, IU School of Medicine
    Global DNA de-methylation is thought to occur only during pre-implantation and gametogenesis in mammals. Scalable, cell-wide de-methylation has not been demonstrated beyond totipotent stages. Here, we observed a large scale de-methylation and subsequent re-methylation (CDR) (including 5-methylcytosine (5mC) and 5-hydroxylmethylcytosine (5hmC)) in post-mitotic cerebellar Purkinje cells (PC) through the course of normal development. Through single cell immuno-identification and cell-specific quantitative methylation assays, we demonstrate that the CDR event is an intrinsically scheduled program, occurring in nearly every PC. Meanwhile, cerebellar granule cells and basket interneurons adopt their own DNA methylation program, independent of PCs. DNA de-methylation was further demonstrated at the gene level, on genes pertinent to PC development. The PC, being one of the largest neurons in the brain, may showcase an amplified epigenetic cycle which may mediate stage transformation including cell cycle arrest, vast axonal-dendritic growth, and synaptogenesis at the onset of neuronal specificity. This discovery is a key step toward better understanding the breadth and role of DNA methylation and de-methylation during neural ontology.
  • Thumbnail Image
    Item
    Detecting Traffic Information From Social Media Texts With Deep Learning Approaches
    (IEEE, 2018-11) Chen, Yuanyuan; Lv, Yisheng; Wang, Xiao; Li, Lingxi; Wang, Fei-Yue; Electrical and Computer Engineering, School of Engineering and Technology
    Mining traffic-relevant information from social media data has become an emerging topic due to the real-time and ubiquitous features of social media. In this paper, we focus on a specific problem in social media mining which is to extract traffic relevant microblogs from Sina Weibo, a Chinese microblogging platform. It is transformed into a machine learning problem of short text classification. First, we apply the continuous bag-of-word model to learn word embedding representations based on a data set of three billion microblogs. Compared to the traditional one-hot vector representation of words, word embedding can capture semantic similarity between words and has been proved effective in natural language processing tasks. Next, we propose using convolutional neural networks (CNNs), long short-term memory (LSTM) models and their combination LSTM-CNN to extract traffic relevant microblogs with the learned word embeddings as inputs. We compare the proposed methods with competitive approaches, including the support vector machine (SVM) model based on a bag of n-gram features, the SVM model based on word vector features, and the multi-layer perceptron model based on word vector features. Experiments show the effectiveness of the proposed deep learning approaches.
  • Thumbnail Image
    Item
    Epigenetic alteration by prenatal alcohol exposure in developing mouse hippocampus and cortex
    (2014-08) Chen, Yuanyuan; Zhou, Feng C.; Jin, Xiao-Ming; Truitt, William A.; Reiter, Jill L.
    Fetal alcohol spectrum disorders (FASD) is the leading neurodevelopment deficit in children born to women who drink alcohol during pregnancy. The hippocampus and cortex are among brain regions vulnerable to alcohol-induced neurotoxicity, and are key regions underlying the cognitive impairment, learning and memory deficits shown in FASD individuals. Hippocampal and cortical neuronal differentiation and maturation are highly influenced by both intrinsic transcriptional signaling and extracellular cues. Epigenetic mechanisms, primarily DNA methylation and histone modifications, are hypothesized to be involved in regulating key neural development events, and are subject to alcohol exposure. Alcohol is shown to modify DNA methylation and histone modifications through altering methyl donor metabolisms. Recent studies in our laboratory have shown that alcohol disrupted genome-wide DNA methylation and delayed early embryonic development. However, how alcohol affects DNA methylation in fetal hippocampal and cortical development remains elusive, therefore, will be the theme of this study. We reported that, in a dietary alcohol-intake model of FASD, prenatal alcohol exposure retarded the development of fetal hippocampus and cortex, accompanied by a delayed cellular DNA methylation program. We identified a programed 5-methylcytosine (5mC) and 5-hydroxylmethylcytosine (5hmC) cellular and chromatic re-organization that was associated with neuronal differentiation and maturation spatiotemporally, and this process was hindered by prenatal alcohol exposure. Furthermore, we showed that alcohol disrupted locus-specific DNA methylation on neural specification genes and reduced neurogenic properties of neural stem cells, which might contribute to the aberration in neurogenesis of FASD individuals. The work of this dissertation suggested an important role of DNA methylation in neural development and elucidated a potential epigenetic mechanism in the alcohol teratogenesis.
  • Thumbnail Image
    Item
    Is 5-Hydroxymethylcytosine a Suppressor or Activator in Epigenetic Marks?
    (Office of the Vice Chancellor for Research, 2013-04-05) Watkins, Darryl S.; Chen, Yuanyuan; Zhou, Feng C.
    Alcohol has been observed to have teratogenic effects on humans and mice during different stages of embryonic development. These effects can be condensed under fetal alcohol spectrum disorder (FASD), exhibiting a variety of signs from growth retardations to neurobehavioral aberrations. Despite better understanding of several potential mechanisms, the question of how alcohol, as an environmental factor leads to brain growth delay in FASD remains elusive. DNA methylation is key to development and tissue specification. Studies have suggested that alcohol may alter gene expression by affecting DNA and histone methylation. Previous studies have demonstrated that 5-methylcytosine (5mC), a DNA methylation mark, is associated with histone 3 lysine-9me3, (H3K9me3) to play a role in gene repression. Recently another methylation mark, 5hydroxylmethylcytosine (5hmC), was found to prevail in the nervous system. However, its function has not been clear. Global analysis suggests that it is a transition of demethylation leading to transcription. The study will first identify its association with histone 3 lysine-4me3, (H3K4me3) a transcriptional activator in gene expression, and then study the 5hmC under influence of alcohol exposure. This study will utilize both an in vivo model—the vapor chamber, and an in vitro model—the embryonic culture system to address this question. Embryos were exposed to alcohol (400mg/dL, 88mM) from the beginning of embryonic day (E) 8 for 6hrs, harvested at E10, and processed for immunohistochemistry. Compare the DNA methylation marks, and histone modification marks to see if the spatial and/or temporal distribution has been affected by alcohol exposure. It is expected that in the alcohol-treated embryos, an overall retardation of embryonic growth, delayed neural tube formation, and altered expression of epigenetic markers will be observed. This study could indicate that alcohol, through alteration of DNA and histone methylation is a potential mechanism underpinning brain growth delay in FASD.
  • Thumbnail Image
    Item
    Strain Differences in Developmental Vulnerability to Alcohol Exposure Via Embryo Culture in Mice
    (Wiley Blackwell (Blackwell Publishing), 2011-07) Chen, Yuanyuan; Ozturk, Nail Can; Ni, Lijun; Goodlett, Charles R.; Zhou, Feng C.; Department of Anatomy & Cell Biology, IU School of Medicine
    Background Prenatal alcohol exposure can result in varying degrees of neurodevelopmental deficits, growth retardation, and facial dysmorphology. Variation in these adverse outcomes not only depends on the dose and pattern of alcohol exposure but also on less well understood interactions among environmental, genetic, and maternal factors. The current study tested the hypothesis that fetal genotype is an important determinant of ethanol teratogenesis by evaluating effects of ethanol exposure via embryo culture in three inbred strains of mice known to differ in the vulnerability of prenatal alcohol exposure in vivo. Methods and results Three strains of mice, C57BL/6N (B6), DBA/2 (D2), and 129S6/SvEvTac (129S6) were assessed in a whole embryo culture beginning on embryonic day 8.25 (E8.25), with or without alcohol administration at 88mM for 6 hours followed by 42 hrs culture in ethanol-free media. Contrasting strain differences in susceptibility were observed for the brain, the face, and other organ systems using the Maele-Fabry and Picard scoring system. The forebrain, midbrain, hindbrain, heart, optic vesicle, caudal neural tube, and hindlimbs of the B6 mice were severely delayed in growth, whereas compared to the respective controls, only the forebrain and optic vesicle were delayed in the D2 mice, and no effects were found in the 129S6 mice. A large number of cleaved(c)-caspase3 positive (+) cells were found in regions of the brain, optic vesicles, cranial nerve nuclei V, VII, VIII, and IX as well as the craniofacial primordial; only a few were found in corresponding regions of the B6 controls. In contrast, only a small number of c-caspase 3-im cells were found in either the alcohol-treated or the controls of the D2 embryos and in 129S6 embryos. The independent apoptotic markers TUNEL and Nile blue staining further confirmed the strain differences in apoptotic responses in both the neural tube and craniofacial primordia. Conclusions Under embryo culture conditions, in which alcohol exposure factors and fetal developmental staging were controlled, and maternal and intrauterine factors were eliminated, the degree of growth retardation and the extent and type of neurodevelopmental teratogenesis varied significantly across strains. Notably, the 129S6 strain was remarkably resistant to alcohol-induced growth deficits, confirming a previous in vivo study, and the D2 strain was also significantly less affected than the B6 strain. These findings demonstrate that fetal genotype is an important factor that can contribute to the variation in fetal alcohol spectrum disorder.