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stem cell epigenetics

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https://www.readbyqxmd.com/read/28225755/intragenic-dna-methylation-prevents-spurious-transcription-initiation
#1
Francesco Neri, Stefania Rapelli, Anna Krepelova, Danny Incarnato, Caterina Parlato, Giulia Basile, Mara Maldotti, Francesca Anselmi, Salvatore Oliviero
In mammals, DNA methylation occurs mainly at CpG dinucleotides. Methylation of the promoter suppresses gene expression, but the functional role of gene-body DNA methylation in highly expressed genes has yet to be clarified. Here we show that, in mouse embryonic stem cells, Dnmt3b-dependent intragenic DNA methylation protects the gene body from spurious RNA polymerase II entry and cryptic transcription initiation. Using different genome-wide approaches, we demonstrate that this Dnmt3b function is dependent on its enzymatic activity and recruitment to the gene body by H3K36me3...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28223921/epigenetic-modulation-of-stem-cells-in-neurodevelopment-the-role-of-methylation-and-acetylation
#2
REVIEW
Martyna Podobinska, Ilona Szablowska-Gadomska, Justyna Augustyniak, Ioanna Sandvig, Axel Sandvig, Leonora Buzanska
The coordinated development of the nervous system requires fidelity in the expression of specific genes determining the different neural cell phenotypes. Stem cell fate decisions during neurodevelopment are strictly correlated with their epigenetic status. The epigenetic regulatory processes, such as DNA methylation and histone modifications discussed in this review article, may impact both neural stem cell (NSC) self-renewal and differentiation and thus play an important role in neurodevelopment. At the same time, stem cell decisions regarding fate commitment and differentiation are highly dependent on the temporospatial expression of specific genes contingent on the developmental stage of the nervous system...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28223506/intragenic-cpg-islands-play-important-roles-in-bivalent-chromatin-assembly-of-developmental-genes
#3
Sun-Min Lee, Jungwoo Lee, Kyung-Min Noh, Won-Young Choi, Sejin Jeon, Goo Taeg Oh, Jeongsil Kim-Ha, Yoonhee Jin, Seung-Woo Cho, Young-Joon Kim
CpG, 5'-C-phosphate-G-3', islands (CGIs) have long been known for their association with enhancers, silencers, and promoters, and for their epigenetic signatures. They are maintained in embryonic stem cells (ESCs) in a poised but inactive state via the formation of bivalent chromatin containing both active and repressive marks. CGIs also occur within coding sequences, where their functional role has remained obscure. Intragenic CGIs (iCGIs) are largely absent from housekeeping genes, but they are found in all genes associated with organ development and cell lineage control...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28222718/abnormal-epigenetic-changes-during-differentiation-of-human-skeletal-muscle-stem-cells-from-obese-subjects
#4
Cajsa Davegårdh, Christa Broholm, Alexander Perfilyev, Tora Henriksen, Sonia García-Calzón, Lone Peijs, Ninna Schiøler Hansen, Petr Volkov, Rasmus Kjøbsted, Jørgen F P Wojtaszewski, Maria Pedersen, Bente Klarlund Pedersen, Dov B Ballak, Charles A Dinarello, Bas Heinhuis, Leo A B Joosten, Emma Nilsson, Allan Vaag, Camilla Scheele, Charlotte Ling
BACKGROUND: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. METHODS: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals...
February 22, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28220199/-novel-pharmaceutical-treatment-approaches-for-gastric-cancer
#5
F Lordick
This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging...
February 20, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28218902/retinoic-acid-directs-breast-cancer-cell-state-changes-through-regulation-of-tet2-pkc%C3%AE-pathway
#6
M-J Wu, M R Kim, Y-S Chen, J-Y Yang, C-J Chang
The key molecular mechanism governing the cancer cell state (stem cell-like state vs differentiation state) to control the cancer stem cell (CSC) pool remains elusive. This study provides the first evidence showing that all-trans retinoic acid (ATRA) induces the interaction and chromatin recruitment of a novel RARβ-TET2 complex to epigenetically activate a specific cohort of gene targets, including MiR-200c. TET2-activated miR-200c further targets and suppresses PKCζ, a cell polarity protein that has a pivotal role in directing asymmetric division of mammalian stem cells to sustain the stem cell pool...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28217689/multiple-roles-of-myc-in-integrating-regulatory-networks-of-pluripotent-stem-cells
#7
REVIEW
Luca Fagnocchi, Alessio Zippo
Pluripotent stem cells (PSCs) are defined by their self-renewal potential, which permits their unlimited propagation, and their pluripotency, being able to generate cell of the three embryonic lineages. These properties render PSCs a valuable tool for both basic and medical research. To induce and stabilize the pluripotent state, complex circuitries involving signaling pathways, transcription regulators and epigenetic mechanisms converge on a core transcriptional regulatory network of PSCs, thus determining their cell identity...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28216148/epigenetic-modification-of-the-ccl5-ccr1-erk-axis-enhances-glioma-targeting-in-dedifferentiation-reprogrammed-bmscs
#8
Rui Chen, Wayne Yuk-Wai Lee, Xiao Hu Zhang, Jie Ting Zhang, Sien Lin, Liang Liang Xu, Biao Huang, Fu Yuan Yang, Hai Long Liu, Bin Wang, Lai Ling Tsang, Sandrine Willaime-Morawek, Gang Li, Hsiao Chang Chan, Xiaohua Jiang
The success of stem cell-mediated gene therapy in cancer treatment largely depends on the specific homing ability of stem cells. We have previously demonstrated that after in vitro induction of neuronal differentiation and dedifferentiation, bone marrow stromal cells (BMSCs) revert to a primitive stem cell population (De-neu-BMSCs) distinct from naive BMSCs. We report here that De-neu-BMSCs express significantly higher levels of chemokines, and display enhanced homing abilities to glioma, the effect of which is mediated by the activated CCL5/CCR1/ERK axis...
February 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28214512/dynamics-and-context-dependent-roles-of-dna-methylation
#9
REVIEW
Christina Ambrosi, Massimiliano Manzo, Tuncay Baubec
DNA methylation is one of the most extensively studied epigenetic marks. It is involved in transcriptional gene silencing, it plays important roles during mammalian development and its perturbation is often associated with human diseases. In mammalian genomes, DNA methylation is a prevalent modification that decorates the majority of cytosines. It is found at the promoters and enhancers of inactive genes, at repetitive elements and within transcribed gene bodies. Its presence at promoters is dynamically linked to gene activity, suggesting that it could directly influence gene expression patterns and cellular identity...
February 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28213207/epimetabolites-discovering-metabolism-beyond-building-and-burning
#10
REVIEW
Megan R Showalter, Tomas Cajka, Oliver Fiehn
Enzymatic transformations of primary, canonical metabolites generate active biomolecules that regulate important cellular and physiological processes. Roles include regulation of histone demethylation in epigenetics, inflammation in tissue injury, insulin sensitivity, cancer cell invasion, stem cell pluripotency status, inhibition of nitric oxide signaling and others. Such modified compounds, defined as epimetabolites, have functions distinct from classic hormones as well as removed from generic anabolism and catabolism...
February 14, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28211918/myotonic-dystrophy-type-1-patient-derived-ipscs-for-the-investigation-of-ctg-repeat-instability
#11
Junko Ueki, Masayuki Nakamori, Masahiro Nakamura, Misato Nishikawa, Yoshinori Yoshida, Azusa Tanaka, Asuka Morizane, Masayoshi Kamon, Toshiyuki Araki, Masanori P Takahashi, Akira Watanabe, Nobuya Inagaki, Hidetoshi Sakurai
Myotonic dystrophy type 1 (DM1) is an autosomal-dominant multi-system disease caused by expanded CTG repeats in dystrophia myotonica protein kinase (DMPK). The expanded CTG repeats are unstable and can increase the length of the gene with age, which worsens the symptoms. In order to establish a human stem cell system suitable for the investigation of repeat instability, DM1 patient-derived iPSCs were generated and differentiated into three cell types commonly affected in DM1, namely cardiomyocytes, neurons and myocytes...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209158/gene-regulatory-network-underlying-the-immortalization-of-epithelial-cells
#12
Luis Fernando Méndez-López, Jose Davila-Velderrain, Elisa Domínguez-Hüttinger, Christian Enríquez-Olguín, Juan Carlos Martínez-García, Elena R Alvarez-Buylla
BACKGROUND: Tumorigenic transformation of human epithelial cells in vitro has been described experimentally as the potential result of spontaneous immortalization. This process is characterized by a series of cell-state transitions, in which normal epithelial cells acquire first a senescent state which is later surpassed to attain a mesenchymal stem-like phenotype with a potentially tumorigenic behavior. In this paper we aim to provide a system-level mechanistic explanation to the emergence of these cell types, and to the time-ordered transition patterns that are common to neoplasias of epithelial origin...
February 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28208656/primetime-for-learning-genes
#13
REVIEW
Joyce Keifer
Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells...
February 11, 2017: Genes
https://www.readbyqxmd.com/read/28207785/dna-methylation-of-the-fthl17-5-upstream-region-regulates-differential-fthl17-expression-in-lung-cancer-cells-and-germline-stem-cells
#14
Nana Aoki, Kentaro Mochizuki, Yasuhisa Matsui
The Ferritin heavy polypeptide-like 17 (Fthl17) gene is a member of the cancer/testis antigen gene family, and is preferentially expressed in cancer cells and in testis. Although DNA methylation has been linked to the regulation of human FTHL17 gene expression, detailed epigenetic regulation of its expression has not been investigated. To address this, we assessed the epigenetic regulation of murine Fthl17 gene expression in cancer cells and germ cells. Fthl17 was more highly expressed in testis, a murine lung cancer cell line, KLN205, and in germline stem cells (GSCs) than in normal lung tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28203307/epigenetic-strategies-to-reverse-drug-resistance-in-heterogeneous-multiple-myeloma
#15
REVIEW
Mark E Issa, Farnaz Sedigheh Takhsha, Chandra Sekhar Chirumamilla, Claudina Perez-Novo, Wim Vanden Berghe, Muriel Cuendet
Multiple myeloma (MM) is a hematological malignancy, which remains incurable because most patients eventually relapse or become refractory to current treatments. Due to heterogeneity within the cancer cell microenvironment, cancer cell populations employ a dynamic survival strategy to chemotherapeutic treatments, which frequently results in a rapid acquisition of therapy resistance. Besides resistance-conferring genetic alterations within a tumor cell population selected during drug treatment, recent findings also reveal non-mutational mechanisms of drug resistance, involving a small population of "cancer stem cells" (CSCs) which are intrinsically more refractory to the effects of a variety of anticancer drugs...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28202042/hoxc8-regulates-self-renewal-differentiation-and-transformation-of-breast-cancer-stem-cells
#16
Mansi Shah, Ryan Cardenas, Belinda Wang, Jenny Persson, Nigel P Mongan, Anna Grabowska, Cinzia Allegrucci
BACKGROUND: Homeobox genes are master regulators of cell fate during embryonic development and their expression is altered in cancer. By regulating the balance between cell proliferation and differentiation, they maintain homeostasis of normal tissues. Here, we screened the expression of homeobox genes in mammary stem cells to establish their role in stem cells transformation in breast cancer. METHODS: Using a Homeobox Genes PCR array, we screened 83 homeobox genes in normal cancer breast stem/progenitor cells isolated by flow cytometry...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28199003/applications-of-induced-pluripotent-stem-cell-technologies-in-spinal-cord-injury
#17
REVIEW
Narihito Nagoshi, Hideyuki Okano
Numerous basic research studies have suggested the potential efficacy of neural precursor cell (NPC) transplantation in spinal cord injury (SCI). However, in most such studies the origin of the cells used was mainly fetal tissue or embryonic stem cells, both of which carry potential ethical concerns with respect to clinical use. The development of induced pluripotent stem cells (iPSCs) opened a new path toward regenerative medicine for SCI. iPSCs can be generated from somatic cells by induction of transcription factors, and induced to differentiate into NPCs with characteristics of cells of the central nervous system...
February 15, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28197667/discovery-and-progress-of-direct-cardiac-reprogramming
#18
REVIEW
Hidenori Kojima, Masaki Ieda
Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs)...
February 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28196481/nuctools-analysis-of-chromatin-feature-occupancy-profiles-from-high-throughput-sequencing-data
#19
Yevhen Vainshtein, Karsten Rippe, Vladimir B Teif
BACKGROUND: Biomedical applications of high-throughput sequencing methods generate a vast amount of data in which numerous chromatin features are mapped along the genome. The results are frequently analysed by creating binary data sets that link the presence/absence of a given feature to specific genomic loci. However, the nucleosome occupancy or chromatin accessibility landscape is essentially continuous. It is currently a challenge in the field to cope with continuous distributions of deep sequencing chromatin readouts and to integrate the different types of discrete chromatin features to reveal linkages between them...
February 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28194114/emerging-molecular-pathways-governing-dietary-regulation-of-neural-stem-cells-during-aging
#20
REVIEW
Chiara de Lucia, Tytus Murphy, Sandrine Thuret
Aging alters cellular and molecular processes, including those of stem cells biology. In particular, changes in neural stem cells (NSCs) are linked to cognitive decline associated with aging. Recently, the systemic environment has been shown to alter both NSCs regulation and age-related cognitive decline. Interestingly, a well-documented and naturally occurring way of altering the composition of the systemic environment is through diet and nutrition. Furthermore, it is well established that the presence of specific nutrients as well as the overall increase or reduction of calorie intake can modulate conserved molecular pathways and respectively reduce or increase lifespan...
2017: Frontiers in Physiology
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