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stem cell epigenetics

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https://www.readbyqxmd.com/read/29351579/lack-of-methyl-cpg-binding-protein-2-mecp2-affects-cell-fate-refinement-during-embryonic-cortical-development
#1
Clementina Cobolli Gigli, Linda Scaramuzza, Marco De Simone, Riccardo L Rossi, Davide Pozzi, Massimiliano Pagani, Nicoletta Landsberger, Francesco Bedogni
During differentiation, neurons progressively restrict their fate repressing the expression of specific genes. Here we describe the involvement in such developmental steps of the methyl-CpG binding protein 2 (MeCP2), an epigenetic factor that participates to chromatin folding and transcriptional regulation. We previously reported that, due to transcriptional impairments, the maturation of Mecp2 null neurons is delayed. To evaluate whether this could stem from altered progenitors proliferation and differentiation, we investigated whether lack of Mecp2 affects these features both in vitro and in vivo...
January 17, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29348326/symmetry-from-asymmetry-or-asymmetry-from-symmetry
#2
Elizabeth W Kahney, Rajesh Ranjan, Ryan J Gleason, Xin Chen
The processes of DNA replication and mitosis allow the genetic information of a cell to be copied and transferred reliably to its daughter cells. However, if DNA replication and cell division were always performed in a symmetric manner, the result would be a cluster of tumor cells instead of a multicellular organism. Therefore, gaining a complete understanding of any complex living organism depends on learning how cells become different while faithfully maintaining the same genetic material. It is well recognized that the distinct epigenetic information contained in each cell type defines its unique gene expression program...
January 18, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29348130/setd1a-protects-hscs-from-activation-induced-functional-decline-in-vivo
#3
Kathrin Arndt, Andrea Kranz, Juliane Fohgrub, Adrien Jolly, Anita S Bledau, Michela Di Virgilio, Mathias Lesche, Andreas Dahl, Thomas Höfer, A Francis Stewart, Claudia Waskow
The regenerative capacity of hematopoietic stem cells (HSCs) is limited by the accumulation of DNA damage. Conditional mutagenesis of the histone 3 lysine 4 (H3K4) methyltransferase, Setd1a, revealed that it is required for the expression of DNA damage recognition and repair pathways in HSCs. Specific deletion of Setd1a in adult long-term (LT)-HSCs is compatible with adult life and has little effect on the maintenance of phenotypic LT-HSCs in the bone marrow. However, SETD1A-deficient LT-HSCs lose their transcriptional cellular identity accompanied by loss of their proliferative capacity and stem cell function under replicative stress in situ and after transplantation...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29343412/implementing-genome-driven-personalized-cardiology-in-clinical-practice
#4
REVIEW
Ares Pasipoularides
Genomics designates the coordinated investigation of a large number of genes in the context of a biological process or disease. It may be long before we attain comprehensive understanding of the genomics of common complex cardiovascular diseases (CVDs) such as inherited cardiomyopathies, valvular diseases, primary arrhythmogenic conditions, congenital heart syndromes, hypercholesterolemia and atherosclerotic heart disease, hypertensive syndromes, and heart failure with preserved/reduced ejection fraction. Nonetheless, as genomics is evolving rapidly, it is constructive to survey now pertinent concepts and breakthroughs...
January 14, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29342143/regulation-of-embryonic-haematopoietic-multipotency-by-ezh1
#5
Linda T Vo, Melissa A Kinney, Xin Liu, Yuannyu Zhang, Jessica Barragan, Patricia M Sousa, Deepak K Jha, Areum Han, Marcella Cesana, Zhen Shao, Trista E North, Stuart H Orkin, Sergei Doulatov, Jian Xu, George Q Daley
All haematopoietic cell lineages that circulate in the blood of adult mammals derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the blood of mammalian embryos, lineage-restricted progenitors arise first, independently of HSCs, which only emerge later in gestation. As best defined in the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post-coitum. Subsequently, erythroid-myeloid progenitors that express fetal haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and the embryo proper, but these cells lack HSC potential...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29341428/epigenetic-silencing-of-tap1-in-aldefluor-breast-cancer-stem-cells-contributes-to-their-enhanced-immune-evasion
#6
Mohammad Sultan, Dejan Vidovic, Arianne S Paine, Thomas T Huynh, Krysta M Coyle, Margaret L Thomas, Brianne M Cruickshank, Cheryl A Dean, Derek R Clements, Youra Kim, Kristin Lee, Shashi A Gujar, Ian C Weaver, Paola Marcato
Avoiding detection and destruction by immune cells is key for tumor initiation and progression. The important role of cancer stem cells (CSC) in tumor initiation has been well established, yet their ability to evade immune detection and targeting is only partly understood. To investigate the ability of breast CSCs to evade immune detection we identified a highly tumorigenic population in a spontaneous murine mammary tumor based on increased aldehyde dehydrogenase (ALDH) activity. We performed tumor growth studies in immunocompetent and immunocompromised mice...
January 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29340787/a-profilin-gene-promoter-from-switchgrass-panicum-virgatum-l-directs-strong-and-specific-transgene-expression-to-vascular-bundles-in-rice
#7
Wenzhi Xu, Wusheng Liu, Rongjian Ye, Mitra Mazarei, Debao Huang, Xinquan Zhang, C Neal Stewart
A switchgrass vascular tissue-specific promoter (PvPfn2) and its 5'-end serial deletions drive high levels of vascular bundle transgene expression in transgenic rice. Constitutive promoters are widely used for crop genetic engineering, which can result in multiple off-target effects, including suboptimal growth and epigenetic gene silencing. These problems can be potentially avoided using tissue-specific promoters for targeted transgene expression. One particularly urgent need for targeted cell wall modification in bioenergy crops, such as switchgrass (Panicum virgatum L...
January 17, 2018: Plant Cell Reports
https://www.readbyqxmd.com/read/29339820/histone-variant-macroh2a1-plays-an-isoform-specific-role-in-suppressing-epithelial-mesenchymal-transition
#8
Dayle Q Hodge, Jihong Cui, Matthew J Gamble, Wenjun Guo
Epithelial-Mesenchymal Transition (EMT) is a biological program that plays key roles in various developmental and pathological processes. Although much work has been done on signaling pathways and transcription factors regulating EMT, the epigenetic regulation of EMT remains not well understood. Histone variants have been recognized as a key group of epigenetic regulators. Among them, macroH2A1 is involved in stem cell reprogramming and cancer progression. We postulated that macroH2A1 may play a role in EMT, a process involving reprogramming of cellular states...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339543/genes-predisposed-to-dna-hypermethylation-during-acquired-resistance-to-chemotherapy-are-identified-in-ovarian-tumors-by-bivalent-chromatin-domains-at-initial-diagnosis
#9
Edward Curry, Constanze Zeller, Nahal Masrour, Darren Patten, John Gallon, Charlotte S Wilhelm-Benartzi, Sadaf Ghaem-Maghami, David D L Bowtell, Robert Brown
Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells aberrantly poised genes may facilitate changes in transcriptional states after exposure to anti-cancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3 and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29339137/oxygen-induced-alterations-in-the-expression-of-chromatin-modifying-enzymes-and-the-transcriptional-regulation-of-imprinted-genes
#10
William M Skiles, Avery Kester, Jane H Pryor, Mark E Westhusin, Michael C Golding, Charles R Long
Embryo culture and assisted reproductive technologies have been associated with a disproportionately high number of epigenetic abnormalities in the resulting offspring. However, the mechanisms by which these techniques influence the epigenome remain poorly defined. In this study, we evaluated the capacity of oxygen concentration to influence the transcriptional control of a selection of key enzymes regulating chromatin structure. In mouse embryonic stem cells, oxygen concentrations modulated the transcriptional regulation of the TET family of enzymes, as well as the de novo methyltransferase Dnmt3a...
January 12, 2018: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29337900/age-related-epigenetic-derangement-upon-reprogramming-and-differentiation-of-cells-from-the-elderly
#11
REVIEW
Francesco Ravaioli, Maria G Bacalini, Claudio Franceschi, Paolo Garagnani
Aging is a complex multi-layered phenomenon. The study of aging in humans is based on the use of biological material from hard-to-gather tissues and highly specific cohorts. The introduction of cell reprogramming techniques posed promising features for medical practice and basic research. Recently, a growing number of studies have been describing the generation of induced pluripotent stem cells (iPSCs) from old or centenarian biologic material. Nonetheless, Reprogramming techniques determine a profound remodelling on cell epigenetic architecture whose extent is still largely debated...
January 16, 2018: Genes
https://www.readbyqxmd.com/read/29337183/temporal-layering-of-signaling-effectors-drives-chromatin-remodeling-during-hair-follicle-stem-cell-lineage-progression
#12
Rene C Adam, Hanseul Yang, Yejing Ge, Wen-Hui Lien, Ping Wang, Yilin Zhao, Lisa Polak, John Levorse, Sanjeethan C Baksh, Deyou Zheng, Elaine Fuchs
Tissue regeneration relies on resident stem cells (SCs), whose activity and lineage choices are influenced by the microenvironment. Exploiting the synchronized, cyclical bouts of tissue regeneration in hair follicles (HFs), we investigate how microenvironment dynamics shape the emergence of stem cell lineages. Employing epigenetic and ChIP-seq profiling, we uncover how signal-dependent transcription factors couple spatiotemporal cues to chromatin dynamics, thereby choreographing stem cell lineages. Using enhancer-driven reporters, mutagenesis, and genetics, we show that simultaneous BMP-inhibitory and WNT signals set the stage for lineage choices by establishing chromatin platforms permissive for diversification...
January 9, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29335068/imprinted-gene-zinc-finger-protein-127-is-a-novel-regulator-of-master-pluripotency-transcription-factor-oct4
#13
Yoo-Wook Kwon, Hyo-Suk Ahn, Joo-Young Park, Han-Mo Yang, Hyun-Jai Cho, Hyo-Soo Kim
Induced pluripotent stem cells (iPSCs) show great promise for replacing current stem cell therapies in the field of regenerative medicine. However, the original method for cellular reprogramming, involving four exogenous transcription factors, is characterized by low efficiency. Here, we focused on using epigenetic modifications to enhance the reprogramming efficiency. We hypothesized that there would be a new reprogramming factor involved in DNA demethylation, acting on the promoters of pluripotency-related genes...
January 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29334780/rules-governing-the-mechanism-of-epigenetic-reprogramming-memory
#14
Phuc-Loi Luu, Daniela Gerovska, Hans R Schöler, Marcos J Araúzo-Bravo
AIM: Disclosing the mechanisms that regulate reprogramming memory. MATERIALS & METHODS: We established computational procedure to find DNA methylation somatic memory sites (SMSs) at single CpGs and integrated them with genomics, epigenomics, transcriptomics and imprinting information. RESULTS & CONCLUSION: Reprogramming memory persists at late passages in low methylated regions. Contrarily to hypomethylated, hypermethylated SMSs occur at evolutionary conserved sites overlapping active transcription loci in dynamic chromatin regions...
January 16, 2018: Epigenomics
https://www.readbyqxmd.com/read/29334242/development-and-disease-in-a-dish-the-epigenetics-of-neurodevelopmental-disorders
#15
Emily Ma Lewis, Kristen L Kroll
Human neurodevelopmental disorders (NDDs) involve mutations in hundreds of individual genes, with over-representation in genes encoding proteins that alter chromatin structure to modulate gene expression. Here, we highlight efforts to model these NDDs through in vitro differentiation of patient-specific induced pluripotent stem cells into neurons. We discuss how epigenetic regulation controls normal cortical development, how mutations in several classes of epigenetic regulators contribute to NDDs, and approaches for modeling cortical development and function using both directed differentiation and formation of cerebral organoids...
January 15, 2018: Epigenomics
https://www.readbyqxmd.com/read/29330145/mbd2-ablation-impairs-lymphopoiesis-and-impedes-progression-and-maintenance-of-t-all
#16
Mi Zhou, Kuangguo Zhou, Ling Cheng, Xing Chen, Jue Wang, Xiao-Min Wang, Yingchi Zhang, Qilin Yu, Shu Zhang, Di Wang, Liang Huang, Mei Huang, Ding Ma, Tao Cheng, Cong-Yi Wang, Weiping Yuan, Jianfeng Zhou
Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic targeting. In this study, we employed a genetically deficient mouse model to explore the role of the methylated DNA binding protein MBD2 in normal and malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional defects of the lymphoid compartment were also observed after in vivo reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an established model of Notch1-driven T cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29328912/bcg-educates-hematopoietic-stem-cells-to-generate-protective-innate-immunity-against-tuberculosis
#17
Eva Kaufmann, Joaquin Sanz, Jonathan L Dunn, Nargis Khan, Laura E Mendonça, Alain Pacis, Fanny Tzelepis, Erwan Pernet, Anne Dumaine, Jean-Christophe Grenier, Florence Mailhot-Léonard, Eisha Ahmed, Jad Belle, Rickvinder Besla, Bruce Mazer, Irah L King, Anastasia Nijnik, Clinton S Robbins, Luis B Barreiro, Maziar Divangahi
The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remain unknown. Here, we show that access of Bacillus Calmette-Guérin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell expansion and enhanced myelopoiesis at the expense of lymphopoiesis...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328786/connections-between-metabolism-and-epigenetics-in-programming-cellular-differentiation
#18
Danielle A Chisolm, Amy S Weinmann
Researchers are intensifying efforts to understand the mechanisms by which changes in metabolic states influence differentiation programs. An emerging objective is to define how fluctuations in metabolites influence the epigenetic states that contribute to differentiation programs. This is because metabolites such as S-adenosylmethionine, acetyl-CoA, α-ketoglutarate, 2-hydroxyglutarate, and butyrate are donors, substrates, cofactors, and antagonists for the activities of epigenetic-modifying complexes and for epigenetic modifications...
January 12, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29327674/insoluble-microenvironment-facilitating-the-generation-and-maintenance-of-pluripotency
#19
Xiaofang Chen, Jiaqi Li, Yan Huang, Peng Liu, Yubo Fan
Induced pluripotent stem cells (iPSCs) hold enormous potential as a tool to generate cells for tissue engineering and regenerative medicine. Since the initial report of iPSCs in 2006, many different methods have been developed in order to enhance the safety and efficiency of this technology. Recent studies indicate that the extracellular signals can promote the production of iPSCs, and even replace the Yamanaka factors. Noticeably, abundant evidences suggest that the insoluble microenvironment, including the culture substrate and neighboring cells, directly regulates the expression of core pluripotency genes and the epigenetic modification of the chromatins, hence impact the reprogramming dynamics...
January 12, 2018: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29327010/dna-methylation-assay-using-droplet-based-dna-melting-curve-analysis
#20
F-W Liu, H-F Liao, S-P Lin, Y-W Lu
DNA methylation is an epigenetic regulation of gene expression, which has drawn great attention in biomedical research due to its association with various diseases. A robust, inexpensive platform to detect and quantify the methylation status in a specific genomic region is necessary. In this study, an on-chip analytical technique of cytosine methylation with droplets in a microchannel is proposed. Genomic DNA samples are encapsulated into a series of droplets and transported through a detection region, where a stable temperature gradient is created...
January 12, 2018: Lab on a Chip
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