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stem cell epigenetics

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https://www.readbyqxmd.com/read/28936481/controlling-epithelial-to-mesenchymal-transition-through-acetylation-of-histone-h2bk5
#1
Robert J Mobley, Amy N Abell
Large-scale epigenetic changes take place when epithelial cells with cell-cell adhesion and apical-basal polarity transition into invasive, individual, mesenchymal cells through a process known as epithelial to mesenchymal transition (EMT). Importantly, cancers with stem cell properties disseminate and form distant metastases by reactivating the developmental EMT program. Recent studies have demonstrated that the epigenetic histone modification, H2BK5 acetylation (H2BK5Ac), is important in the regulation of EMT...
September 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28935813/asxl3-is-a-novel-pluripotency-factor-in-human-respiratory-epithelial-cells-and-a-potential-therapeutic-target-in-small-cell-lung-cancer
#2
Vivek Shukla, Mahadev Rao, Hongen Zhang, Jeanette Beers, Darawalee Wangsa, Danny Wangsa, Floryne O Buishand, Yonghong Wang, Zhiya Yu, Holly Stevenson, Emily Reardon, Kaitlin C McLoughlin, Andrew Kaufman, Eden Payabyab, Julie A Hong, Mary Zhang, Sean R Davis, Daniel C Edelman, Guokai Chen, Markku Miettinen, Nicholas Restfo, Thomas Ried, Paul S Meltzer, David S Schrump
In this study, we generated induced pluripotent stem cells (iPSC) from normal human small airway epithelial cells (SAEC) to investigate epigenetic mechanisms of stemness and pluripotency in lung cancers. We documented key hallmarks of reprogramming in lung iPSC (Lu-iPSC) that coincided with modulation of more than 15,000 genes relative to parental SAEC. Of particular novelty, we identified the PRC2-associated protein, ASXL3 which was markedly upregulated in Lu-iPSC and small cell lung cancer (SCLC) lines and clinical specimens...
September 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28934561/epigenetic-mechanisms-regulating-adaptive-responses-to-targeted-kinase-inhibitors-in-cancer
#3
Steven P Angus, Jon S Zawistowski, Gary L Johnson
Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance...
September 15, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28934364/the-histone-variant-macroh2a-confers-functional-robustness-to-the-intestinal-stem-cell-compartment
#4
Ryan James Cedeno, Angela Nakauka-Ddamba, Maryam Yousefi, Stephanie Sterling, Nicolae Adrian Leu, Ning Li, John R Pehrson, Christopher Joachim Lengner
A stem cell's epigenome directs cell fate during development, homeostasis, and regeneration. Epigenetic dysregulation can lead to inappropriate cell fate decisions, aberrant cell function, and even cancer. The histone variant macroH2A has been shown to influence gene expression, guide cell fate, and safeguard against genotoxic stress. Interestingly, mice lacking functional macroH2A histones (hereafter referred to as macroH2A DKO) are viable and fertile; yet suffer from increased perinatal death and reduced weight and size compared to wildtype (WT)...
2017: PloS One
https://www.readbyqxmd.com/read/28933369/epigenetic-mechanisms-of-tamoxifen-resistance-in-luminal-breast-cancer
#5
REVIEW
Hany A Abdel-Hafiz
Breast cancer is one of the most common cancers and the second leading cause of cancer death in the United States. Estrogen receptor (ER)-positive cancer is the most frequent subtype representing more than 70% of breast cancers. These tumors respond to endocrine therapy targeting the ER pathway including selective ER modulators (SERMs), selective ER downregulators (SERDs) and aromatase inhibitors (AIs). However, resistance to endocrine therapy associated with disease progression remains a significant therapeutic challenge...
July 6, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28928129/new-advances-and-challenges-of-targeting-cancer-stem-cells
#6
Nurmaa K Dashzeveg, Rokana Taftaf, Erika K Ramos, Luke Torre-Healy, Anastasia Chumakova, Daniel J Silver, Tyler J Alban, Maksim Sinyuk, Praveena S Thiagarajan, Awad M Jarrar, Soumya M Turaga, Caner Saygin, Erin Mulkearns-Hubert, Masahiro Hitomi, Jeremy N Rich, Stanton L Gerson, Justin D Lathia, Huiping Liu
The second International Cancer Stem Cell Conference in Cleveland, Ohio, on September 20-23, 2016, convened 330 attendees from academic, industrial, and clinical organizations. It featured a debate on the concepts and challenges of the cancer stem cells (CSC) as well as CSC-centered scientific sessions on clinical trials, genetics and epigenetics, tumor microenvironment, immune suppression, metastasis, therapeutic resistance, and emerging novel concepts. The conference hosted 35 renowned speakers, 100 posters, 20 short talks, and a preconference workshop...
September 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28925404/ing5-activity-in-self-renewal-of-glioblastoma-stem-cells-via-calcium-and-follicle-stimulating-hormone-pathways
#7
F Wang, A Y Wang, C Chesnelong, Y Yang, A Nabbi, S Thalappilly, V Alekseev, K Riabowol
Stem cell-like brain tumor initiating cells (BTICs) cause recurrence of glioblastomas, with BTIC 'stemness' affected by epigenetic mechanisms. The ING family of epigenetic regulators (ING1-5) function by targeting histone acetyltransferase (HAT) or histone deacetylase complexes to the H3K4me3 mark to alter histone acetylation and subsequently, gene expression. Here we find that ectopic expression of ING5, the targeting subunit of HBO1, MOZ and MORF HAT complexes increases expression of the Oct4, Olig2 and Nestin stem cell markers, promotes self-renewal, prevents lineage differentiation and increases stem cell pools in BTIC populations...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28923849/bivalent-epigenetic-control-of-oncofetal-gene-expression-in-cancer
#8
Sayyed K Zaidi, Seth E Frietze, Jonathan A Gordon, Jessica L Heath, Terri Messier, Deli Hong, Joseph R Boyd, Mingu Kang, Anthony N Imbalzano, Jane B Lian, Janet L Stein, Gary S Stein
Multiple mechanisms of epigenetic control that include DNA methylation, histone modification, non-coding RNAs, and mitotic gene bookmarking play pivotal roles in stringent gene regulation during lineage commitment and maintenance. Experimental evidence indicates that bivalent chromatin domains, i.e., regions of genome that are marked by both H3K4me3 (activating) and H3K27me3 (repressive) histone modifications, are a key property of pluripotent stem cells. Bivalency of developmental genes during the G1 phase of the pluripotent stem cell cycle contributes to cell fate decisions...
September 18, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28919441/a-unique-ph-dependent-recognition-of-methylated-histone-h3k4-by-pps-and-dido
#9
Adam H Tencer, Jovylyn Gatchalian, Brianna J Klein, Abid Khan, Yi Zhang, Brian D Strahl, Karel H M van Wely, Tatiana G Kutateladze
The protein partner of Sans-fille (PPS) and its human homolog DIDO mediate diverse chromatin activities, including the regulation of stemness genes in embryonic stem cells and splicing in Drosophila. Here, we show that the PHD fingers of PPS and DIDO recognize the histone mark H3K4me3 in a pH-dependent manner: the binding is enhanced at high pH values but is decreased at low pH. Structural analysis reveals that the pH dependency is due to the presence of a histidine residue in the K4me3-binding aromatic cage of PPS...
September 8, 2017: Structure
https://www.readbyqxmd.com/read/28916764/rapid-and-reversible-epigenome-editing-by-endogenous-chromatin-regulators
#10
Simon M G Braun, Jacob G Kirkland, Emma J Chory, Dylan Husmann, Joseph P Calarco, Gerald R Crabtree
Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916494/transflammation-innate-immune-signaling-in-nuclear-reprogramming
#11
Shu Meng, Palas Chanda, Rajarajan A Thandavarayan, John P Cooke
Induction of pluripotency in somatic cells by retroviral overexpression of four transcription factors has revolutionized the field of stem cell biology and regenerative medicine. The efficient induction of pluripotency requires the activation of innate immune signaling in a process termed "transflammation" [1]. Specifically, the stimulation of pattern recognition receptors (PRRs) causes global alterations in the expression and activity of epigenetic modifiers to favor an open chromatin configuration. Activation of toll-like receptors (TLR) or RIG-1-like receptors (RLR) [2] trigger signaling cascades that result in NFκB or IRF-3 mediated changes in epigenetic plasticity that facilitate reprogramming...
September 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28915715/epigenetic-regulation-during-the-differentiation-of-stem-cells-to-germ-cells
#12
REVIEW
Yuan-Chao Sun, Yong-Yong Wang, Wei Ge, Shun-Feng Cheng, Paul W Dyce, Wei Shen
Gametogenesis is an essential process to ensure the transfer of genetic information from one generation to the next. It also provides a mechanism by which genetic evolution can take place. Although the genome of primordial germ cells (PGCs) is exactly the same with somatic cells within an organism, there are significant differences between their developments. For example, PGCs eventually undergo meiosis to become functional haploid gametes, and prior to that they undergo epigenetic imprinting which greatly alter their genetic regulation...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913935/induction-of-cancer-cell-stemness-by-depletion-of-macrohistone-h2a1-in-hepatocellular-carcinoma
#13
Oriana Lo Re, Caterina Fusilli, Francesca Rappa, Matthias Van Haele, Julien Douet, Jana Pindjakova, Sura Wanessa Rocha, Illar Pata, Barbora Valčíková, Stjepan Uldrijan, Raymond S Yeung, Christina Alves Peixoto, Tania Roskams, Marcus Buschbeck, Tommaso Mazza, Manlio Vinciguerra
Hepatocellular carcinomas (HCC) contain a sub-population of cancer stem cells (CSCs), which exhibit stem-cell like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic cell reprogramming...
September 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28912427/dna-methylation-profiling-reveals-common-signatures-of-tumorigenesis-and-defines-epigenetic-prognostic-subtypes-of-canine-diffuse-large-b-cell-lymphoma
#14
Serena Ferraresso, Arianna Aricò, Tiziana Sanavia, Silvia Da Ros, Massimo Milan, Luciano Cascione, Stefano Comazzi, Valeria Martini, Mery Giantin, Barbara Di Camillo, Sandro Mazzariol, Diana Giannuzzi, Laura Marconato, Luca Aresu
Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5'-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912174/senescence-is-a-spi1-pu-1-induced-anti-proliferative-mechanism-in-primary-hematopoietic-cells
#15
Laure Delestré, Cui Hengxiang, Michela Esposito, Cyril Quiveron, Elena Mylonas, Virginie Penard-Lacronique, Oliver Bischof, Christel Guillouf
Transcriptional deregulation caused by epigenetic or genetic alterations is a major cause of leukemic transformation. The Spi1/PU.1 transcription factor is a key regulator of many steps of hematopoiesis, and limits self-renewal of hematopoietic stem cells. The deregulation of its expression or activity contributes to leukemia, in which Spi1 can be either an oncogene or a tumor suppressor. Here, we explored whether cellular senescence, an anti-tumoral pathway that restrains cell proliferation, is a mechanism by which Spi1 limits hematopoietic cells expansion, and thus prevents the development of leukemia...
September 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28910694/an-epidemiologic-perspective-on-the-stem-cell-hypothesis-in-human-carcinogenesis
#16
REVIEW
David Schottenfeld
BACKGROUND: Tomasetti and Vogelstein have hypothesized that the patterns of cancer incidence in various cells and tissues are highly correlated with the estimated lifetime number of stem cell divisions. The authors reviewed the risks in tissues of 17 types of cancer from the United States and 69 additional countries. Positive correlations were observed consistently between the tissue - specific cancer incidence and the estimated lifetime number of stem cell divisions. The authors concluded that approximately two-thirds of global cancer incidence may be attributed to random DNA replication errors...
September 11, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28910138/hsp90-inhibition-and-cellular-stress-elicits-phenotypic-plasticity-in-hematopoietic-differentiation
#17
Abdalla A Lawag, Jennifer M Napper, Caroline A Hunter, Nickolas A Bacon, Seth Deskins, Manaf El-Hamdani, Sarah-Leigh Govender, Emine C Koc, Vincent E Sollars
Cancer cells exist in a state of Darwinian selection using mechanisms that produce changes in gene expression through genetic and epigenetic alteration to facilitate their survival. Cellular plasticity, or the ability to alter cellular phenotype, can assist in survival of premalignant cells as they progress to full malignancy by providing another mechanism of adaptation. The connection between cellular stress and the progression of cancer has been established, although the details of the mechanisms have yet to be fully elucidated...
September 14, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28903899/the-application-of-next-generation-sequencing-techniques-in-studying-transcriptional-regulation-in-embryonic-stem-cells
#18
Ya-Jun Liu, Feng Zhang, Hong-de Liu, Xiao Sun
The mechanism of transcriptional regulation has been the focus of many studies in the post-genomic era. The development of sequencing-based technologies for chromatin profiling enables current researchers to experimentally measure chromatin properties. Moreover, many studies aim at annotating the state of the chromatin into broad categories based on observed chromatin features and/or DNA sequences, then associating the resultant distal regulatory regions with the correct target genes based on DNA sequences, and predicting the dependence of epigenetic features on genetic variation...
August 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28903624/repair-of-calvarial-bone-defect-using-jarid1a-knockdown-bone-mesenchymal-stem-cells-in-rats
#19
Yuan Deng, Tao Guo, Jipeng Li, Li Guo, Ping Gu, Xianqun Fan
Histone methylation is regarded as an important epigenetic event during stem cell differentiation. Jumonji AT-rich interactive domain 1A (Jarid1a) is a histone demethylase that specifically catalyzes demethylation of dimethyl or trimethyl histone H3K4me3, which is normally associated with transcriptionally active genes. Runt-related transcription factor 2 (Runx2) has been identified as a key transcription factor in the early stage of osteogenesis. A better understanding of this epigenetic mechanism that governs osteogenic differentiation of bone mesenchymal stem cells (BMSCs) can provide new insights into BMSCs based bone tissue engineering...
September 13, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28903311/development-of-hepatoma-derived-bidirectional-oval-like-cells-as-a-model-to-study-host-interactions-with-hepatitis-c-virus-during-differentiation
#20
Masahiko Ito, Suofeng Sun, Takasuke Fukuhara, Ryosuke Suzuki, Miho Tamai, Toyohiko Yamauchi, Kenji Nakashima, Yoh-Ichi Tagawa, Shigetoshi Okazaki, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki
Directed differentiation of human stem cells including induced pluripotent stem cells into hepatic cells potentially leads to acquired susceptibility to hepatitis C virus (HCV) infection. However, cellular determinants that change their expression during cell reprogramming or hepatic differentiation and are pivotal for supporting the HCV life cycle remain unclear. In this study, by introducing a set of reprogramming factors, we established HuH-7-derived oval-like cell lines, Hdo-17 and -23, which possess features of bipotential liver precursors...
August 15, 2017: Oncotarget
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