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https://www.readbyqxmd.com/read/28545252/cpg-and-non-cpg-methylation-in-epigenetic-gene-regulation-and-brain-function
#1
REVIEW
Hyun Sik Jang, Woo Jung Shin, Jeong Eon Lee, Jeong Tae Do
DNA methylation is a major epigenetic mark with important roles in genetic regulation. Methylated cytosines are found primarily at CpG dinucleotides, but are also found at non-CpG sites (CpA, CpT, and CpC). The general functions of CpG and non-CpG methylation include gene silencing or activation depending on the methylated regions. CpG and non-CpG methylation are found throughout the whole genome, including repetitive sequences, enhancers, promoters, and gene bodies. Interestingly, however, non-CpG methylation is restricted to specific cell types, such as pluripotent stem cells, oocytes, neurons, and glial cells...
May 23, 2017: Genes
https://www.readbyqxmd.com/read/28545230/nanog-plays-a-hierarchical-role-in-the-transcription-network-regulating-the-pluripotency-and-plasticity-of-adipose-tissue-derived-stem-cells
#2
Maria Pitrone, Giuseppe Pizzolanti, Laura Tomasello, Antonina Coppola, Lorenzo Morini, Gianni Pantuso, Romina Ficarella, Valentina Guarnotta, Sebastio Perrini, Francesco Giorgino, Carla Giordano
The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self-renewal potential and differentiation capacity. Our aim was to study the different expression of the embryonic stem cell markers NANOG (homeobox protein NANOG), SOX2 (SRY (sex determining region Y)-box 2) and OCT4 (octamer-binding transcription factor 4) and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28545044/differentiation-of-spontaneously-contracting-cardiomyocytes-from-non-virally-reprogrammed-human-amniotic-fluid-stem-cells
#3
Aaron J Velasquez-Mao, Christopher J M Tsao, Madeline N Monroe, Xavier Legras, Beatrice Bissig-Choisat, Karl-Dimiter Bissig, Rodrigo Ruano, Jeffrey G Jacot
Congenital heart defects are the most common birth defect. The limiting factor in tissue engineering repair strategies is an autologous source of functional cardiomyocytes. Amniotic fluid contains an ideal cell source for prenatal harvest and use in correction of congenital heart defects. This study aims to investigate the potential of amniotic fluid-derived stem cells (AFSC) to undergo non-viral reprogramming into induced pluripotent stem cells (iPSC) followed by growth-factor-free differentiation into functional cardiomyocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28544655/3d-bioprinting-human-induced-pluripotent-stem-cell-constructs-for-in-situ-cell-proliferation-and-successive-multilineage-differentiation
#4
Qi Gu, Eva Tomaskovic-Crook, Gordon G Wallace, Jeremy M Crook
The ability to create 3D tissues from induced pluripotent stem cells (iPSCs) is poised to revolutionize stem cell research and regenerative medicine, including individualized, patient-specific stem cell-based treatments. There are, however, few examples of tissue engineering using iPSCs. Their culture and differentiation is predominantly planar for monolayer cell support or induction of self-organizing embryoids (EBs) and organoids. Bioprinting iPSCs with advanced biomaterials promises to augment efforts to develop 3D tissues, ideally comprising direct-write printing of cells for encapsulation, proliferation, and differentiation...
May 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28544378/concise-review-induced-pluripotent-stem-cell-based-drug-discovery-for-mitochondrial-disease
#5
REVIEW
Gizem Inak, Carmen Lorenz, Pawel Lisowski, Annika Zink, Barbara Mlody, Alessandro Prigione
High attrition rates and loss of capital plague the drug discovery process. This is particularly evident for mitochondrial disease that typically involves neurological manifestations and is caused by nuclear or mitochondrial DNA defects. This group of heterogeneous disorders is difficult to target because of the variability of the symptoms among individual patients and the lack of viable modeling systems. The use of induced pluripotent stem cells (iPSCs) might significantly improve the search for effective therapies for mitochondrial disease...
May 22, 2017: Stem Cells
https://www.readbyqxmd.com/read/28544217/towards-a-crispr-picture-use-of-crispr-cas9-to-model-diseases-in-human-stem-cells-in-vitro
#6
Jamie L Freiermuth, Ian J Powell-Castilla, G Ian Gallicano
Human induced pluripotent stem cells (iPSCs) can be differentiated into any cell in the body unlocking enormous research potential. Combined with the recent discovery of CRISPR/Cas9 endonucleases in bacteria and their modification for use in biomedical research, these methods have the potential to revolutionize the field of genetic engineering and open the door to generating in vitro models that more closely resemble the in vivo system than ever before. Use of CRISPR/Cas9 has created a whirlwind within the scientific community in the last few years, as the race to move beyond just disease analysis and towards the goal of gene and cell therapy moves further...
May 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543863/prmt8-controls-the-pluripotency-and-mesodermal-fate-of-human-embryonic-stem-cells-by-enhancing-the-pi3k-akt-sox2-axis
#7
Ho-Chang Jeong, Soon-Jung Park, Jong-Jin Choi, Young-Hyun Go, Soon-Ki Hong, Ok-Seon Kwon, Joong-Gon Shin, Rae-Kwon Kim, Mi-Ok Lee, Su-Jae Lee, Hyoung Doo Shin, Sung-Hwan Moon, Hyuk-Jin Cha
Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferases 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions...
May 20, 2017: Stem Cells
https://www.readbyqxmd.com/read/28543595/stem-cell-therapy-a-new-therapeutic-option-for-cardiovascular-diseases
#8
Nasser Hashemi Goradel, Farshid Ghiyami SHoor, Babak Negahdari, Ziba Vaisi Malekshahi, Milad Hashemzehi, Aria Masoudifar, Hamed Mirzaei
Cardiovascular diseases are known as one of major causes of morbidity and mortality worldwide. Despite the many advancement in therapies are associated with cardiovascular diseases, it seems that finding of new therapeutic option is necessary. Cell therapy is one of attractive therapeutic platforms for treatment of a variety of diseases such as cardiovascular diseases. Among of various types of cell therapy, stem cell therapy has been emerged as an effective therapeutic approach in this area. Stem cells divided into multipotent stem cells and pluripotent stem cells...
May 25, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543529/kir2-1-and-k2p1-channels-reconstitute-two-levels-of-resting-membrane-potential-in-cardiomyocytes
#9
Dongchuan Zuo, Kuihao Chen, Min Zhou, Zheng Liu, Haijun Chen
Strong inward rectifier K(+) (Kir2) channels primarily maintain normal resting membrane potential of cardiomyocytes. In sub-physiological extracellular K(+) concentrations or pathological hypokalaemia, human cardiomyocytes show both hyperpolarized and depolarized resting membrane potentials; these depolarized potentials cause cardiac arrhythmia; however, the underlying mechanism is unknown. Here we show that Kir2.1 currents non-linearly counterbalance hypokalaemia-induced K2P1 leak cation currents, reconstituting two levels of resting membrane potential in cardiomyocytes...
May 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28543424/how-to-rethink-the-fourteen-day-rule
#10
Sarah Chan
Recently, attention has been drawn to the basic principles governing the use of human embryos in research: specifically, the so-called fourteen-day rule. This rule stipulates that human embryos should not be allowed to grow in vitro past fourteen days of development. For years, the fourteen-day limit was largely theoretical, since culture techniques were not sufficient to maintain embryos up to this point. Yet in the past year, research has suggested that growing embryos beyond fourteen days might be feasible and scientifically valuable...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28542487/characterization-of-micrornas-expression-profiles-in-human-dental-derived-pluripotent-stem-cells
#11
Xiaobing Tan, Qingyuan Dai
Induced pluripotent stem cells (iPSCs) technology provides a powerful means to generate and regenerate unlimited pluripotent stem cells directly from body tissue cells. Stem cells from apical papilla (SCAP) and Dental pulp stem cells (DPSCs) are present in 'cell-rich zones' within the dental pulp region, which are capable of regenerating pulp and dentin tissues in vivo. In this study, we investigated the difference of miRNAs expression in SCAPs and DPSCs before and after the reprogramming. Using miRNA microarray, 134 and 265 differentially expressed miRNAs in DPSCs- and SCAP-iPSCs were up-regulated compared to these before reprogramming...
2017: PloS One
https://www.readbyqxmd.com/read/28541509/evidence-that-phosphorylated-ubiquitin-signaling-is-involved-in-the-etiology-of-parkinson-s-disease
#12
Kahori Shiba-Fukushima, Kei-Ichi Ishikawa, Tsuyoshi Inoshita, Nana Izawa, Masashi Takanashi, Shigeto Sato, Osamu Onodera, Wado Akamatsu, Hideyuki Okano, Yuzuru Imai, Nobutaka Hattori
The ubiquitin (Ub) kinase PINK1 and the E3 Ub ligase Parkin, two gene products associated with young-onset Parkinson's disease (PD), participate in mitochondrial quality control. The phosphorylation of mitochondrial polyUb by PINK1, which is activated in a mitochondrial membrane potential (ΔΨm)-dependent manner, facilitates the mitochondrial translocation and concomitant enzymatic activation of Parkin, leading to the clearance of phospho-polyUb-tagged mitochondria via mitophagy. Thus, Ub phosphorylation is a key event in PINK1-Parkin-mediated mitophagy...
May 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28541275/engineering-the-haemogenic-niche-mitigates-endogenous-inhibitory-signals-and-controls-pluripotent-stem-cell-derived-blood-emergence
#13
Nafees Rahman, Patrick M Brauer, Lilian Ho, Tatiana Usenko, Mukul Tewary, Juan Carlos Zúñiga-Pflücker, Peter W Zandstra
Efforts to recapitulate haematopoiesis, a process guided by spatial and temporal inductive signals, to generate haematopoietic progenitors from human pluripotent stem cells (hPSCs) have focused primarily on exogenous signalling pathway activation or inhibition. Here we show haemogenic niches can be engineered using microfabrication strategies by micropatterning hPSC-derived haemogenic endothelial (HE) cells into spatially-organized, size-controlled colonies. CD34+VECAD+ HE cells were generated with multi-lineage potential in serum-free conditions and cultured as size-specific haemogenic niches that displayed enhanced blood cell induction over non-micropatterned cultures...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28541271/protein-altering-and-regulatory-genetic-variants-near-gata4-implicated-in-bicuspid-aortic-valve
#14
Bo Yang, Wei Zhou, Jiao Jiao, Jonas B Nielsen, Michael R Mathis, Mahyar Heydarpour, Guillaume Lettre, Lasse Folkersen, Siddharth Prakash, Claudia Schurmann, Lars Fritsche, Gregory A Farnum, Maoxuan Lin, Mohammad Othman, Whitney Hornsby, Anisa Driscoll, Alexandra Levasseur, Marc Thomas, Linda Farhat, Marie-Pierre Dubé, Eric M Isselbacher, Anders Franco-Cereceda, Dong-Chuan Guo, Erwin P Bottinger, G Michael Deeb, Anna Booher, Sachin Kheterpal, Y Eugene Chen, Hyun Min Kang, Jacob Kitzman, Heather J Cordell, Bernard D Keavney, Judith A Goodship, Santhi K Ganesh, Gonçalo Abecasis, Kim A Eagle, Alan P Boyle, Ruth J F Loos, Per Eriksson, Jean-Claude Tardif, Chad M Brummett, Dianna M Milewicz, Simon C Body, Cristen J Willer
Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28540181/dynamic-regulation-of-small-rnaome-during-the-early-stage-of-cardiac-differentiation-from-pluripotent-embryonic-stem-cells
#15
Yue Li, An Zeng, Ge Li, Ya-Na Guan, Huang-Tian Yang, Bairong Shen, Qing Jing
Embryonic stem cells (mESCs), having potential to differentiate into three germ-layer cells including cardiomyocytes, shall be a perfect model to help understanding heart development. Here, using small RNA deep sequencing, we studied the small RNAome in the early stage of mouse cardiac differentiation. We found that the expression pattern of most microRNA (miRNA) were highly enriched at the beginning and declined thereafter, some were still insufficiently expressed on day 6, and most miRNAs recovered in the following days...
June 2017: Genomics Data
https://www.readbyqxmd.com/read/28539972/site-specific-regulation-of-histone-h1-phosphorylation-in-pluripotent-cell-differentiation
#16
Ruiqi Liao, Craig A Mizzen
BACKGROUND: Structural variation among histone H1 variants confers distinct modes of chromatin binding that are important for differential regulation of chromatin condensation, gene expression and other processes. Changes in the expression and genomic distributions of H1 variants during cell differentiation appear to contribute to phenotypic differences between cell types, but few details are known about the roles of individual H1 variants and the significance of their disparate capacities for phosphorylation...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28539859/human-induced-pluripotent-stem-cells-generated-neural-cells-behaving-like-brain-and-spinal-cord-cells-an-insight-into-the-involvement-of-retinoic-acid-and-sonic-hedgehog-proteins
#17
Akinlolu Abdulazeez Adelaja
OBJECTIVES: The previous studies generated neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) using different protocols. However, the nature of the temporal or regional specificity of NPCs derived using these protocols is not well defined. Therefore, this study aimed to generate age- and region-specific NPCs from hiPSCs, which mimic in vivo fetal brain (FNPC-B) or spinal cord (FNPC-SC) tissues, in the absence or presence of retinoic acid (RA) and sonic hedgehog (SHH)...
April 2017: International Journal of Health Sciences
https://www.readbyqxmd.com/read/28539832/recapitulating-and-correcting-marfan-syndrome-in-a-cellular-model
#18
Jung Woo Park, Li Yan, Chris Stoddard, Xiaofang Wang, Zhichao Yue, Leann Crandall, Tiwanna Robinson, Yuxiao Chang, Kyle Denton, Enqin Li, Bin Jiang, Zhenwu Zhang, Kristen Martins-Taylor, Siu-Pok Yee, Hong Nie, Feng Gu, Wei Si, Ting Xie, Lixia Yue, Ren-He Xu
Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in FBN1 gene, which encodes a key extracellular matrix protein FIBRILLIN-1. The haplosufficiency of FBN1 has been implicated in pathogenesis of MFS with manifestations primarily in cardiovascular, muscular, and ocular tissues. Due to limitations in animal models to study the late-onset diseases, human pluripotent stem cells (PSCs) offer a homogeneic tool for dissection of cellular and molecular pathogenic mechanism for MFS in vitro. Here, we first derived induced PSCs (iPSCs) from a MFS patient with a FBN1 mutation and corrected the mutation, thereby generating an isogenic "gain-of-function" control cells for the parental MFS iPSCs...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28539611/an-episomal-vector-based-crispr-cas9-system-for-highly-efficient-gene-knockout-in-human-pluripotent-stem-cells
#19
Yifang Xie, Daqi Wang, Feng Lan, Gang Wei, Ting Ni, Renjie Chai, Dong Liu, Shijun Hu, Mingqing Li, Dajin Li, Hongyan Wang, Yongming Wang
Human pluripotent stem cells (hPSCs) represent a unique opportunity for understanding the molecular mechanisms underlying complex traits and diseases. CRISPR/Cas9 is a powerful tool to introduce genetic mutations into the hPSCs for loss-of-function studies. Here, we developed an episomal vector-based CRISPR/Cas9 system, which we called epiCRISPR, for highly efficient gene knockout in hPSCs. The epiCRISPR system enables generation of up to 100% Insertion/Deletion (indel) rates. In addition, the epiCRISPR system enables efficient double-gene knockout and genomic deletion...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539554/investigation-of-the-pathogenesis-of-autoimmune-diseases-by-ips-cells
#20
Bunki Natsumoto, Hirofumi Shoda, Keishi Fujio, Makoto Otsu, Kazuhiko Yamamoto
  The pluripotent stem cells have a self-renewal ability and can be differentiated into theoretically all of cell types. The induced pluripotent stem (iPS) cells overcame the ethical problems of the human embryonic stem (ES) cell, and enable pathologic analysis of intractable diseases and drug discovery. The in vitro disease model using disease-specific iPS cells enables repeated analyses of human cells without influence of environment factors. Even though autoimmune diseases are polygenic diseases, autoimmune disease-specific iPS cells are thought to be a promising tool for analyzing the pathogenesis of the diseases and drug discovery in future...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
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