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stem cell epigenetics

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https://www.readbyqxmd.com/read/27909741/the-role-of-epigenetic-modifiers-in-extended-cultures-of-functional-hepatocyte-like-cells-derived-from-human-neonatal-mesenchymal-stem-cells
#1
M Cipriano, J C Correia, S P Camões, N G Oliveira, P Cruz, H Cruz, M Castro, J L Ruas, J M Santos, J P Miranda
The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO)...
December 1, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27905327/potential-therapeutic-effect-of-epigenetic-therapy-on-treatment-induced-neuroendocrine-prostate-cancer
#2
Xiang Xu, Yu-Hua Huang, Yan-Jing Li, Alexa Cohen, Zhen Li, Jill Squires, Wei Zhang, Xu-Feng Chen, Min Zhang, Jiao-Ti Huang
Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model (LNCaP/NE1.8) to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy...
November 29, 2016: Asian Journal of Andrology
https://www.readbyqxmd.com/read/27903646/whole-transcriptome-sequencing-identified-a-distinct-subtype-of-acute-lymphoblastic-leukemia-with-predominant-genomic-abnormalities-of-ep300-and-crebbp
#3
Maoxiang Qian, Hui Zhang, Shirley Kow-Yin Kham, Shuguang Liu, Chuang Jiang, Xujie Zhao, Yi Lu, Charnise Goodings, Ting-Nien Lin, Ranran Zhang, Takaya Moriyama, Zhaohong Yin, Zhenhua Li, Thuan Chong Quah, Hany Ariffin, Ah Moy Tan, Shuhong Shen, Deepa Bhojwani, Shaoyan Hu, Suning Chen, Huyong Zheng, Ching-Hon Pui, Allen Eng-Juh Yeoh, Jun J Yang
Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54...
November 30, 2016: Genome Research
https://www.readbyqxmd.com/read/27900567/clinical-potential-of-human-induced-pluripotent-stem-cells-perspectives-of-induced-pluripotent-stem-cells
#4
REVIEW
Dharmendra Kumar, Taruna Anand, Wilfried A Kues
The recent establishment of induced pluripotent stem (iPS) cells promises the development of autologous cell therapies for degenerative diseases, without the ethical concerns associated with human embryonic stem (ES) cells. Initially, iPS cells were generated by retroviral transduction of somatic cells with core reprogramming genes. To avoid potential genotoxic effects associated with retroviral transfection, more recently, alternative non-viral gene transfer approaches were developed. Before a potential clinical application of iPS cell-derived therapies can be planned, it must be ensured that the reprogramming to pluripotency is not associated with genome mutagenesis or epigenetic aberrations...
November 29, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27900345/new-insight-into-lsd1-function-in-human-cortical-neurogenesis
#5
Kazumi Hirano, Masakazu Namihira
The cerebral cortex of primates has evolved massively and intricately in comparison to that of other species. Accumulating evidence indicates that this is caused by changes in cell biological features of neural stem cells (NSCs), which differentiate into neurons and glial cells during development. The fate of NSCs during rodent cortical development is stringently regulated by epigenetic factors, such as histone modification enzymes, but the role of these factors in human corticogenesis is largely unknown. We have recently discovered that a lysine-specific demethylase 1 (LSD1), which catalyzes the demethylation of methyl groups in the histone tail, plays a unique role in human fetal NSCs (hfNSCs)...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27900343/divergence-and-rewiring-of-regulatory-networks-for-neural-development-between-human-and-other-species
#6
COMMENT
Ping Wang, Dejian Zhao, Shira Rockowitz, Deyou Zheng
Neural and brain development in human and other mammalian species are largely similar, but distinct features exist at the levels of macrostructure and underlying genetic control. Comparative studies of epigenetic regulation and transcription factor (TF) binding in humans, chimpanzees, rodents, and other species have found large differences in gene regulatory networks. A recent analysis of the cistromes of REST/NRSF, a critical transcriptional regulator for the nervous system, demonstrated that REST binding to syntenic genomic regions (i...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27899651/a-permissive-chromatin-state-regulated-by-zfp281-aff3-in-controlling-the-imprinted-meg3-polycistron
#7
Yan Wang, Yang Shen, Qian Dai, Qian Yang, Yue Zhang, Xin Wang, Wei Xie, Zhuojuan Luo, Chengqi Lin
Genomic imprinting is an epigenetic regulation that leads to gene expression in a parent-of-origin specific manner. AFF3, the central component of the Super Elongation Complex-like 3 (SEC-L3), is enriched at both the intergenic-differentially methylated region (IG-DMR) and the Meg3 enhancer within the imprinted Dlk1-Dio3 locus to regulate the allele-specific gene expression in this locus. The localization of AFF3 to IG-DMR requires ZFP57. However, how AFF3 functions at the Meg3 enhancer in maintaining allele-specific gene expression remains unclear...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899508/optimized-inducible-shrna-and-crispr-cas9-platforms-for-in-vitro-studies-of-human-development-using-hpscs
#8
Alessandro Bertero, Matthias Pawlowski, Daniel Ortmann, Kirsten Snijders, Loukia Yiangou, Miguel Cardoso de Brito, Stephanie Brown, William G Bernard, James D Cooper, Elisa Giacomelli, Laure Gambardella, Nicholas R F Hannan, Dharini Iyer, Fotios Sampaziotis, Felipe Serrano, Mariëlle C F Zonneveld, Sanjay Sinha, Mark Kotter, Ludovic Vallier
Inducible loss of gene function experiments are necessary to uncover mechanisms underlying development, physiology and disease. However, current methods are complex, lack robustness and do not work in multiple cell types. Here we address these limitations by developing single-step optimized inducible gene knockdown or knockout (sOPTiKD or sOPTiKO) platforms. These are based on genetic engineering of human genomic safe harbors combined with an improved tetracycline-inducible system and CRISPR/Cas9 technology...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mkk7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#9
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-Ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: -Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical pro-arrhythmic side effects, culminating in a greater risk of sudden death. METHODS: -We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 (MKK7) deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harbouring MKK7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs)...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27897123/the-epigenetic-regulation-in-tooth-development-and-regeneration
#10
Yao Lin, Liwei Zheng, Li Fan, Wei Kuang, Rui Guo, Jiong Lin, Jiahua Wu, Jiali Tan
Teeth are formed through sequential and reciprocal interactions between epithelial and mesenchymal tissues and they are essential to physical and psychological health. In-depth knowledge of tooth development, from histology to the underlying mechanisms, is necessary for the regeneration of lost teeth. Therefore, the review firstly introduced tooth development, and summarized the use of tooth-derived stem cells. To date, epigenetic regulation has been shown to have roles in numerous activities, including odontogenesis...
November 29, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27895716/widespread-recovery-of-methylation-at-gametic-imprints-in-hypomethylated-mouse-stem-cells-following-rescue-with-dnmt3a2
#11
Avinash Thakur, Sarah-Jayne Mackin, Rachelle E Irwin, Karla M O'Neill, Gareth Pollin, Colum Walsh
BACKGROUND: Imprinted loci are paradigms of epigenetic regulation and are associated with a number of genetic disorders in human. A key characteristic of imprints is the presence of a gametic differentially methylated region (gDMR). Previous studies have indicated that DNA methylation lost from gDMRs could not be restored by DNMT1, or the de novo enzymes DNMT3A or 3B in stem cells, indicating that imprinted regions must instead undergo passage through the germline for reprogramming. However, previous studies were non-quantitative, were unclear on the requirement for DNMT3A/B and showed some inconsistencies...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27894957/dna-methylation-profiling-identifies-ptrf-cavin-1-as-a-novel-tumor-suppressor-in-ewing-sarcoma-when-co-expressed-with-caveolin-1
#12
Juan Huertas-Martínez, Franck Court, Santiago Rello-Varona, David Herrero-Martín, Olga Almacellas-Rabaiget, Miguel Sáinz-Jaspeado, Silvia Garcia-Monclús, Laura Lagares-Tena, Raquel Buj, Lourdes Hontecillas-Prieto, Ana Sastre, Daniel Azorin, Xavier Sanjuan, Roser López-Alemany, Sebastian Moran, Josep Roma, Soledad Gallego, Jaume Mora, Xavier García Del Muro, Paloma H Giangrande, Miquel A Peinado, Javier Alonso, Enrique de Alava, Dave Monk, Manel Esteller, Oscar M Tirado
Epigenetic modifications have been shown to be important in developmental tumors as Ewing sarcoma. We profiled the DNA methylation status of 15 primary tumors, 7 cell lines, 10 healthy tissues and 4 human mesenchymal stem cells lines samples using the Infinium Human Methylation 450k. Differential methylation analysis between Ewing sarcoma and reference samples revealed 1,166 hypermethylated and 864 hypomethylated CpG sites (Bonferroni p<0.05, δ-β-value with absolute difference of >0.20) corresponding to 392 and 470 genes respectively...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27893710/muc1-c-activates-bmi1-in-human-cancer-cells
#13
M Hiraki, T Maeda, A Bouillez, M Alam, A Tagde, K Hinohara, Y Suzuki, T Markert, M Miyo, K Komura, R Ahmad, H Rajabi, D Kufe
B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is a component of the polycomb repressive complex 1 (PRC1) complex that is overexpressed in breast and other cancers, and promotes self-renewal of cancer stem-like cells. The oncogenic mucin 1 (MUC1) C-terminal (MUC1-C) subunit is similarly overexpressed in human carcinoma cells and has been linked to their self-renewal. There is no known relationship between MUC1-C and BMI1 in cancer. The present studies demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism in breast and other cancer cells...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27890672/epigenetics-of-cell-fate-reprogramming-and-its-implications-for-neurological-disorders-modelling
#14
REVIEW
Maciej Grzybek, Aleksandra Golonko, Marta Walczak, Pawel Lisowski
The reprogramming of human induced pluripotent stem cells (hiPSCs) proceeds in a stepwise manner with reprogramming factors binding and epigenetic composition changes during transition to maintain the epigenetic landscape, important for pluripotency. There arises a question as to whether the aberrant epigenetic state after reprogramming leads to epigenetic defects in induced stem cells causing unpredictable long term effects in differentiated cells. In this review, we present a comprehensive view of epigenetic alterations accompanying reprogramming, cell maintenance and differentiation as factors that influence applications of hiPSCs in stem cell based technologies...
November 23, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27889084/linking-telomere-regulation-to-stem-cell-pluripotency
#15
REVIEW
Lin Liu
Embryonic stem cells (ESCs), somatic cell nuclear transfer ESCs, and induced pluripotent stem cells (iPSCs) represent the most studied group of PSCs. Unlimited self-renewal without incurring chromosomal instability and pluripotency are essential for the potential use of PSCs in regenerative therapy. Telomere length maintenance is critical for the unlimited self-renewal, pluripotency, and chromosomal stability of PSCs. While telomerase has a primary role in telomere maintenance, alternative lengthening of telomere pathways involving recombination and epigenetic modifications are also required for telomere length regulation, notably in mouse PSCs...
November 23, 2016: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27886392/deregulated-expression-of-ezh2-in-congenital-brainstem-disconnection
#16
P G Barth, E Aronica, S Fox, K Fluiter, M A J Weterman, A Poretti, D C Miller, E Boltshauser, B Harding, M Santi, F Baas
Congenital brainstem disconnection (CBSD) is an enigmatic embryo-fetal defect presenting as (sub)total absence of a segment between mesencephalon and lower brainstem. Rostro-caudal limits of the defect vary while the basal pons is always involved and the cerebellum is globally hypoplastic. A recent update and review[1] lists 14 cases, including 3 brain autopsy studies[1-3]. Necrosis and glial- or inflammatory reactions were absent. Inferior olivary nuclei were small or absent, pontine nuclei depleted, and the cerebellar dentate nuclei dysplastic...
November 25, 2016: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/27875275/histone-chaperone-aplf-regulates-induction-of-pluripotency-in-murine-fibroblasts
#17
Khaja Mohieddin Syed, Sunu Joseph, Ananda Mukherjee, Aditi Majumder, Jose M Teixeira, Debasree Dutta, Madhavan Radhakrishna Pillai
Induction of pluripotency in differentiated cells by the exogenous expression of transcription factors, Oct4, Sox2, Klf4 and cMyc, involves reprogramming at the epigenetic level. Histones and their metabolism governed by histone chaperones constitute a significant aspect of epigenetics. We hypothesized that histone chaperones might facilitate or inhibit the course of reprogramming. For the first time, we report here that the downregulation of histone chaperone Aprataxin PNK-like factor (APLF) promotes reprogramming by augmenting the expression of E-cadherin (Cdh1), implicated in mesenchymal-to-epithelial transition (MET) involved in the generation of induced pluripotent stem cells (iPSCs) from mouse embryonic fibroblasts (MEFs)...
November 14, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27872698/the-role-of-exosomes-contents-on-genetic-and-epigenetic-alterations-of-recipient-cancer-cells
#18
REVIEW
Golnoush Dehbashi Behbahani, Soghra Khani, Hamideh Mahmoodzadeh Hosseini, Kazem Abbaszadeh-Goudarzi, Saeed Nazeri
Exosomes, as a mediator of cell-to-cell transfer of genetic information, act an important role in intercommunication between tumor cells and their niche including fibroblasts, endothelial cells, adipocytes and monocytes. Several studies have shown that tumor cells can influence their neighboring cells by releasing exosomes. These exosomes provide signaling cues for stimulation, activation, proliferation and differentiation of cells. Exosomes contain mRNAs, microRNAs (miRNA), and proteins that could be transferred to target cells inducing genetic and epigenetic changes...
October 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27868040/inhibition-of-mll1-histone-methyltransferase-brings-the-developmental-clock-back-to-na%C3%A3-ve-pluripotency
#19
COMMENT
Stefan Muller, Arnab Nayak
Embryonic stem cells (ESCs) and the post-implantation epiblast stem cells (EpiSCs) portray two different states of pluripotency. They differ with respect to epigenetic signatures, dependency of growth factor signaling circuit and cell morphology. They are interconvertible, however, with poor reconversion efficiency. This is indicative of existence of other unknown regulatory pathways govern developmental stage transition. Zhang and colleagues have recently demonstrated that pharmacological inhibition of MLL1 histone methyltransferase is casually linked to efficient reprogramming of EpiSCs to developmentally competent ESCs...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27868038/as-sirt-ing-the-role-of-an-epigenetic-modifier-in-hematopoietic-stem-cell-homeostasis
#20
COMMENT
Andrew Magimaidas, Rachit Badolia, Priyanka Madireddi, Dheeraj Bhavanasi
No abstract text is available yet for this article.
2016: Stem Cell Investigation
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