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https://www.readbyqxmd.com/read/28329681/sirt6-promotes-dna-end-joining-in-ipscs-derived-from-old-mice
#1
Wen Chen, Nana Liu, Hongxia Zhang, Haiping Zhang, Jing Qiao, Wenwen Jia, Songcheng Zhu, Zhiyong Mao, Jiuhong Kang
Induced pluripotent stem cells (iPSCs) have great potential for treating age-related diseases, but the genome integrity of iPSCs is critically important. Here, we demonstrate that non-homologous end joining (NHEJ), rather than homologous recombination (HR), is less efficient in iPSCs from old mice than young mice. We further find that Sirt6 is downregulated in iPSCs from old mice. Sirt6 directly binds to Ku80 and facilitates the Ku80/DNA-PKcs interaction, thus promoting DNA-PKcs phosphorylation at residue S2056, leading to efficient NHEJ...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28329675/trimethylation-and-acetylation-of-%C3%AE-catenin-at-lysine-49-represent-key-elements-in-esc-pluripotency
#2
Katrin Hoffmeyer, Dirk Junghans, Benoit Kanzler, Rolf Kemler
Wnt/β-catenin signaling is required for embryonic stem cell (ESC) pluripotency by inducing mesodermal differentiation and inhibiting neuronal differentiation; however, how β-catenin counter-regulates these differentiation pathways is unknown. Here, we show that lysine 49 (K49) of β-catenin is trimethylated (β-catMe3) by Ezh2 or acetylated (β-catAc) by Cbp. Significantly, β-catMe3 acts as a transcriptional co-repressor of the neuronal differentiation genes sox1 and sox3, whereas β-catAc acts as a transcriptional co-activator of the key mesodermal differentiation gene t-brachyury (t-bra)...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28329361/sex-hormones-affect-outcome-in-arrhythmogenic-right-ventricular-cardiomyopathy-dysplasia-from-a-stem-cell-derived-cardiomyocyte-based-model-to-clinical-biomarkers-of-disease-outcome
#3
Deniz Akdis, Ardan M Saguner, Khooshbu Shah, Chuanyu Wei, Argelia Medeiros-Domingo, Arnold von Eckardstein, Thomas F Lüscher, Corinna Brunckhorst, H S Vincent Chen, Firat Duru
Aims: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by fibrofatty infiltration of the myocardium and ventricular arrhythmias that may lead to sudden cardiac death. It has been observed that male patients develop the disease earlier and present with more severe phenotypes as compared to females. Thus, we hypothesized that serum levels of sex hormones may contribute to major arrhythmic cardiovascular events (MACE) in patients with ARVC/D. Methods and results: The serum levels of five sex hormones, sex hormone-binding globulin, high sensitivity troponin T, pro-brain natriuretic peptide, cholesterol, triglycerides, insulin, and glucose were measured in 54 ARVC/D patients (72% male)...
February 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28328900/beasts-of-burden-large-animal-chimeras-using-human-pluripotent-stem-cells
#4
Dustin M Graham
No abstract text is available yet for this article.
March 22, 2017: Lab Animal
https://www.readbyqxmd.com/read/28327660/quantitative-volumetric-raman-imaging-of-three-dimensional-cell-cultures
#5
Charalambos Kallepitis, Mads S Bergholt, Manuel M Mazo, Vincent Leonardo, Stacey C Skaalure, Stephanie A Maynard, Molly M Stevens
The ability to simultaneously image multiple biomolecules in biologically relevant three-dimensional (3D) cell culture environments would contribute greatly to the understanding of complex cellular mechanisms and cell-material interactions. Here, we present a computational framework for label-free quantitative volumetric Raman imaging (qVRI). We apply qVRI to a selection of biological systems: human pluripotent stem cells with their cardiac derivatives, monocytes and monocyte-derived macrophages in conventional cell culture systems and mesenchymal stem cells inside biomimetic hydrogels that supplied a 3D cell culture environment...
March 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28327633/cardiac-drug-drug-interaction-between-hcv-ns5b-pronucleotide-inhibitors-and-amiodarone-is-determined-by-their-specific-diastereochemistry
#6
Armando Lagrutta, Christopher P Regan, Haoyu Zeng, John P Imredy, Kenneth Koeplinger, Pierre Morissette, Liping Liu, Gordon Wollenberg, Christopher Brynczka, José Lebrón, Joseph DeGeorge, Frederick Sannajust
Severe bradycardia/bradyarrhythmia following coadministration of the HCV-NS5B prodrug sofosbuvir with amiodarone was recently reported. Our previous preclinical in vivo experiments demonstrated that only certain HCV-NS5B prodrugs elicit bradycardia when combined with amiodarone. In this study, we evaluate the impact of HCV-NS5B prodrug phosphoramidate diastereochemistry (D-/L-alanine, R-/S-phosphoryl) in vitro and in vivo. Co-applied with amiodarone, L-ala,SP prodrugs increased beating rate and decreased beat amplitude in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), but D-ala,RP produgs, including MK-3682, did not...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327614/partial-reprogramming-of-pluripotent-stem-cell-derived-cardiomyocytes-into-neurons
#7
Wenpo Chuang, Arun Sharma, Praveen Shukla, Guang Li, Moritz Mall, Kuppusamy Rajarajan, Oscar J Abilez, Ryoko Hamaguchi, Joseph C Wu, Marius Wernig, Sean M Wu
Direct reprogramming of somatic cells has been demonstrated, however, it is unknown whether electrophysiologically-active somatic cells derived from separate germ layers can be interconverted. We demonstrate that partial direct reprogramming of mesoderm-derived cardiomyocytes into neurons is feasible, generating cells exhibiting structural and electrophysiological properties of both cardiomyocytes and neurons. Human and mouse pluripotent stem cell-derived CMs (PSC-CMs) were transduced with the neurogenic transcription factors Brn2, Ascl1, Myt1l and NeuroD...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327192/dna-double-strand-breaks-in-human-induced-pluripotent-stem-cell-reprogramming-and-long-term-in-vitro-culturing
#8
Pavel Simara, Lenka Tesarova, Daniela Rehakova, Pavel Matula, Stanislav Stejskal, Ales Hampl, Irena Koutna
BACKGROUND: Human induced pluripotent stem cells (hiPSCs) play roles in both disease modelling and regenerative medicine. It is critical that the genomic integrity of the cells remains intact and that the DNA repair systems are fully functional. In this article, we focused on the detection of DNA double-strand breaks (DSBs) by phosphorylated histone H2AX (known as γH2AX) and p53-binding protein 1 (53BP1) in three distinct lines of hiPSCs, their source cells, and one line of human embryonic stem cells (hESCs)...
March 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28327113/low-cell-number-single-tube-amplification-sta-of-total-rna-revealed-transcriptome-changes-from-pluripotency-to-endothelium
#9
Yi-Hsuan Lee, Ya-Wen Hsueh, Yao-Hung Peng, Kung-Chao Chang, Kuen-Jer Tsai, H Sunny Sun, Ih-Jen Su, Po-Min Chiang
BACKGROUND: In addition to messenger RNA (mRNA), noncoding RNAs (ncRNAs) are essential components in cellular machineries for translation and splicing. Besides their housekeeping functions, ncRNAs are involved in cell type-specific regulation of translation, mRNA stability, genome structure, and accessibility. To have a comprehensive understanding of the identities and functions of different cell types, a method to comprehensively quantify both mRNA and ncRNA in a sensitive manner is highly desirable...
March 21, 2017: BMC Biology
https://www.readbyqxmd.com/read/28326803/when-is-an-alveolar-type-2-cell-an-alveolar-type-2-cell-a-conundrum-for-lung-stem-cell-biology-and-regenerative-medicine
#10
Michael F Beers, Yuben Moodley
Generating mature, differentiated, adult lung cells from pluripotent cells such as induced pluripotent cells (iPS) and embryonic stem cells (ES) offers the hope of both generating disease specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung regenerative medicine, several groups have developed and reported on protocols utilizing either defined media, co-culture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors...
March 22, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28326715/-role-of-dna-methylation-in-regulation-of-osteogenic-differentiation-of-stem-cells
#11
Shen Yu, Yang Pu, Hao Jin, Jing Dian, Tang Ge, Zhao Zhihe
DNA methylation and demethylation are two important mechanisms of epigenetics, which is important in the study of cell differentiation, proliferation, and senescence. During osteogenic differentiation of stem cells, the expression of osteogenic specific genes and demethylated promoters is upregulated, whereas the expression of pluripotent genes and hypermethylated promoters is downregulated. The dynamic changes and balance between DNA methylation and demethylation are important for the coordination of gene expression and the inhibition of improper phenotypes...
October 1, 2016: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28326324/three-dimensional-human-cardiac-tissue-engineered-by-centrifugation-of-stacked-cell-sheets-and-cross-sectional-observation-of-its-synchronous-beatings-by-optical-coherence-tomography
#12
Yuji Haraguchi, Akiyuki Hasegawa, Katsuhisa Matsuura, Mari Kobayashi, Shin-Ichi Iwana, Yasuhiro Kabetani, Tatsuya Shimizu
Three-dimensional (3D) tissues are engineered by stacking cell sheets, and these tissues have been applied in clinical regenerative therapies. The optimal fabrication technique of 3D human tissues and the real-time observation system for these tissues are important in tissue engineering, regenerative medicine, cardiac physiology, and the safety testing of candidate chemicals. In this study, for aiming the clinical application, 3D human cardiac tissues were rapidly fabricated by human induced pluripotent stem (iPS) cell-derived cardiac cell sheets with centrifugation, and the structures and beatings in the cardiac tissues were observed cross-sectionally and noninvasively by two optical coherence tomography (OCT) systems...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28326305/implications-for-a-stem-cell-regenerative-medicine-based-approach-to-human-intervertebral-disk-degeneration
#13
REVIEW
Petra Kraus, Thomas Lufkin
The human body develops from a single cell, the zygote, the product of the maternal oocyte and the paternal spermatozoon. That 1-cell zygote embryo will divide and eventually grow into an adult human which is comprised of ~3.7 × 10(13) cells. The tens of trillions of cells in the adult human can be classified into approximately 200 different highly specialized cell types that make up all of the different tissues and organs of the human body. Regenerative medicine aims to replace or restore dysfunctional cells, tissues and organs with fully functional ones...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28325684/monitoring-and-visualizing-microrna-dynamics-during-live-cell-differentiation-using-microrna-responsive-non-viral-reporter-vectors
#14
Hideyuki Nakanishi, Kenji Miki, Kaoru R Komatsu, Masayuki Umeda, Megumi Mochizuki, Azusa Inagaki, Yoshinori Yoshida, Hirohide Saito
MicroRNA (miRNA) activity differs with cell type, suggesting it can be used as a cell marker. In this study, we developed novel miRNA-responsive non-viral reporter vectors to continuously monitor and visualize miRNA dynamics during differentiation and to efficiently purify target living cells. Each vector codes miRNA-responsive and reference reporter genes in a single mRNA. These two genes are independent modules but transcribed by a single promoter, which enables us to distinguish miRNA-mediated post-transcriptional repression from transcriptional repression...
March 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28325300/one-step-biallelic-and-scarless-correction-of-a-%C3%AE-thalassemia-mutation-in-patient-specific-ipscs-without-drug-selection
#15
Yali Liu, Yi Yang, Xiangjin Kang, Bin Lin, Qian Yu, Bing Song, Ge Gao, Yaoyong Chen, Xiaofang Sun, Xiaoping Li, Lei Bu, Yong Fan
Monogenic disorders (MGDs), which are caused by single gene mutations, have a serious effect on human health. Among these, β-thalassemia (β-thal) represents one of the most common hereditary hematological diseases caused by mutations in the human hemoglobin β (HBB) gene. The technologies of induced pluripotent stem cells (iPSCs) and genetic correction provide insights into the treatments for MGDs, including β-thal. However, traditional approaches for correcting mutations have a low efficiency and leave a residual footprint, which leads to some safety concerns in clinical applications...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325116/stem-cell-markers-describe-a-transition-from-somatic-to-pluripotent-cell-states-in-a-rat-model-of-endometriosis
#16
Essam Rashad Othman, Fatma Yassine Meligy, Ayat Abdel-Rahman Sayed, Mohamed Ahmed El-Mokhtar, Abeer Mohamed Refaiy
OBJECTIVE: To study Thy1 as a fibroblast marker, SSEA1 as a marker of intermediate pluripotency, and Oct4 as a marker of established pluripotency in rat model of endometriosis. DESIGN: In vivo animal study. MATERIALS AND METHODS: Endometriosis was induced in 20 albino female rats through autologous transplantation of one uterine horn to mesentery of intestine. Other 20 rats had their horn removed without transplantation (controls). Rats were sacrificed 4 weeks after induction surgery...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28324490/assessment-of-mitophagy-in-ips-cell-derived-neurons
#17
Kei-Ichi Ishikawa, Akihiro Yamaguchi, Hideyuki Okano, Wado Akamatsu
Aberrant mitochondrial function is associated with many neurological diseases. Mitophagy is a key mechanism for the elimination of damaged mitochondria and maintenance of mitochondrial homeostasis. Induced pluripotent stem (iPS) cell technologies developed over the last decade have allowed us to analyze functions of the human neuron. Here we describe an efficient induction method from human iPS cells to neurons, followed by an image-based mitophagy assay.
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324485/maintenance-of-human-embryonic-stem-cells-by-sphingosine-1-phosphate-and-platelet-derived-growth-factor
#18
Raymond C B Wong, Martin F Pera, Alice Pébay
Human embryonic stem cells (hESCs) have historically been cultivated on feeder layers of primary mouse embryonic fibroblasts (MEF) in a medium supplemented with fetal calf serum (FCS). However, serum contains a wide variety of biologically active compounds that might adversely affect hESC growth and differentiation. Thus, cultivation of stem cells in FCS complicates experimental approaches to define the intracellular mechanisms required for hESC maintenance. This chapter describes the serum-free maintenance of hESCs in culture by addition of sphingosine-1-phosphate (S1P) and platelet-derived growth factor (PDGF)...
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28323620/discovery-of-novel-determinants-of-endothelial-lineage-using-chimeric-heterokaryons
#19
Wing Tak Wong, Gianfranco Matrone, XiaoYu Tian, Simion Alin Tomoiaga, Kin Fai Au, Shu Meng, Sayumi Yamazoe, Daniel Sieveking, Kaifu Chen, David M Burns, James K Chen, Helen M Blau, John P Cooke
We wish to identify determinants of endothelial lineage. Murine embryonic stem cells (mESC) were fused with human endothelial cells in stable, non-dividing, heterokaryons. Using RNA-seq it is possible to discriminate between human and mouse transcripts in these chimeric heterokaryons. We observed a temporal pattern of gene expression in the ESCs of the heterokaryons that recapitulated ontogeny, with early mesodermal factors being expressed before mature endothelial genes. A set of transcriptional factors not known to be involved in endothelial development was upregulated, one of which was POU class 3 homeobox 2 (Pou3f2)...
March 21, 2017: ELife
https://www.readbyqxmd.com/read/28322920/stem-cell-transplantation-therapy-for-multifaceted-therapeutic-benefits-after-stroke
#20
REVIEW
Ling Wei, Zheng Z Wei, Michael Qize Jiang, Osama Mohamad, Shan Ping Yu
One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures...
March 16, 2017: Progress in Neurobiology
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