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https://www.readbyqxmd.com/read/28922739/o-glcnac-transferase-regulates-transcriptional-activity-of-human-oct4
#1
Sandii Constable, Jae-Min Lim, Krithika Vaidyanathan, Lance Wells
O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar modification found on many different classes of nuclear and cytoplasmic proteins. Addition of this modification, by the enzyme O-linked N-acetylglucosamine transferase (OGT), is dynamic and inducible. One major class of proteins modified by O-GlcNAc is transcription factors. O-GlcNAc regulates transcription factor properties through a variety of different mechanisms including localization, stability and transcriptional activation. Maintenance of embryonic stem (ES) cell pluripotency requires tight regulation of several key transcription factors, many of which are modified by O-GlcNAc...
October 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28921486/expression-of-concern-to-evaluation-of-patients-with-multiple-sclerosis-using-reverse-nutech-functional-score-and-expanded-disability-status-scale-after-human-embryonic-stem-cell-therapy
#2
Geeta Shroff
The Editors-in-Chief of Clinical and Translational Medicine are issuing an editorial expression of concern to alert readers that concerns have been raised regarding the ethics of this study [1]. Appropriate editorial action will be taken once this has been fully investigated. The author disagrees with this notice.
September 18, 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28921476/expression-of-concern-to-role-of-physiotherapy-in-the-mobilization-of-patients-with-spinal-cord-injury-undergoing-human-embryonic-stem-cells-transplantation
#3
Geeta Shroff, Dipin Thakur, Varun Dhingra, Deepak Singh Baroli, Deepanshu Khatri, Rahul Dev Gautam
The Editors-in-Chief of Clinical and Translational Medicine are issuing an editorial expression of concern to alert readers that concerns have been raised regarding the ethics of this study [1]. Appropriate editorial action will be taken once this has been fully investigated. Geeta Shroff disagrees with this notice. Dipin Thakur, Varun Dhingra, Deepak Singh Baroli, Deepanshu Khatri and Rahul Dev Gautam have not responded to our correspondence about this article.
September 18, 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28920958/the-n-6-methyladenosine-m-6-a-forming-enzyme-mettl3-controls-myeloid-differentiation-of-normal-hematopoietic-and-leukemia-cells
#4
Ly P Vu, Brian F Pickering, Yuanming Cheng, Sara Zaccara, Diu Nguyen, Gerard Minuesa, Timothy Chou, Arthur Chow, Yogesh Saletore, Matthew MacKay, Jessica Schulman, Christopher Famulare, Minal Patel, Virginia M Klimek, Francine E Garrett-Bakelman, Ari Melnick, Martin Carroll, Christopher E Mason, Samie R Jaffrey, Michael G Kharas
N(6)-methyladenosine (m(6)A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether the m(6)A modification controls the differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m(6)A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells (HSPCs) promotes cell differentiation, coupled with reduced cell proliferation. Conversely, overexpression of wild-type METTL3, but not of a catalytically inactive form of METTL3, inhibits cell differentiation and increases cell growth...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28919441/a-unique-ph-dependent-recognition-of-methylated-histone-h3k4-by-pps-and-dido
#5
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/28919263/single-cell-gene-expression-analysis-of-a-human-esc-model-of-pancreatic-endocrine-development-reveals-different-paths-to-%C3%AE-cell-differentiation
#6
Maja Borup Kjær Petersen, Ajuna Azad, Camilla Ingvorsen, Katja Hess, Mattias Hansson, Anne Grapin-Botton, Christian Honoré
The production of insulin-producing β cells from human embryonic stem cells (hESCs) in vitro represents a promising strategy for a cell-based therapy for type 1 diabetes mellitus. To explore the cellular heterogeneity and temporal progression of endocrine progenitors and their progeny, we performed single-cell qPCR on more than 500 cells across several stages of in vitro differentiation of hESCs and compared them with human islets. We reveal distinct subpopulations along the endocrine differentiation path and an early lineage bifurcation toward either polyhormonal cells or β-like cells...
September 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28918520/derivation-of-human-induced-pluripotent-stem-cell-ipsc-lines-and-mechanism-of-pluripotency-historical-perspective-and-recent-advances
#7
REVIEW
Arvind Chhabra
Derivation of human embryonic stem cell (hES) lines in 1998 was not only a major technological breakthrough in the field of regenerative medicine; it also triggered a passionate debate about the ethical issues associated with the utilization of human embryos for derivation of hESC lines. Successful derivation of induced pluripotent stem cell (iPS) lines from human somatic cells with defined reprogramming factors by Shinya Yamanaka`s group in 2007 was another breakthrough that generated enormous excitement and hope for the development of donor-specific personalized cell replacement therapies (CRT) without the ethical dilemma associated with it...
September 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28917518/genome-stability-of-programmed-stem-cell-products
#8
REVIEW
Ulrich Martin
Inherited and acquired genomic abnormalities are known to cause genetic diseases and contribute to cancer formation. Recent studies demonstrated a substantial mutational load in mouse and human embryonic and induced pluripotent stem cells (ESCs and iPSCs). Single nucleotide variants, copy number variations, and larger chromosomal abnormalities may influence the differentiation capacity of pluripotent stem cells and the functionality of their derivatives in disease modelling and drug screening, and are considered a serious risk for cellular therapies based on ESC or iPSC derivatives...
September 13, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28916725/characterization-of-enhancers-and-the-role-of-the-transcription-factor-klf7-in-regulating-corneal-epithelial-differentiation
#9
Rachel Herndon Klein, William Hu, Ghaidaa Kashgari, Ziguang Lin, Tuyen Nguyen, Michael Doan, Bogi Andersen
During tissue development, transcription factors bind regulatory DNA regions called enhancers, often located at great distances from the genes they regulate, to control gene expression. The enhancer landscape during embryonic stem cell differentiation has been well characterized. By contrast, little is known about the shared and unique enhancer regulatory mechanisms in different ectodermally derived epithelial cells. Here, we use ChIP-seq to identify domains enriched for histone marks H3K4me3, H3K4me1, and H3K27ac, and define for the first time the super enhancers and typical enhancers active in primary human corneal epithelial cells...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28914568/human-embryonic-stem-cell-derived-mesenchymal-stromal-cells-decrease-the-development-of-severe-experimental-autoimmune-uveitis-in-b10-riii-mice
#10
Yu Qin, Ann M Chan, Yu-Ling Chang, Anna Matynia, Nicholas A Kouris, Erin A Kimbrel, Negin Ashki, Sachin Parikh, Michael B Gorin, Robert Lanza, Ralph D Levinson, Lynn K Gordon
PURPOSE: We investigated the effect of exogenously administered human embryonic stem cell-derived mesenchymal stromal cells (hESC-MSCs) in experimental autoimmune uveitis (EAU) in B10.RIII mice, a murine model of severe uveitis. METHODS: B10.RIII mice were immunized with an uveitogenic peptide, and intraperitoneal injections of 5 million hESC-MSCs per animal were given on the same day. Behavioral light sensitivity assays, histological evaluation, cytokine production, and regulatory T cells were analyzed at the peak of the disease...
September 15, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28913662/effects-of-short-term-exposure-to-sevoflurane-on-the-survival-proliferation-apoptosis-and-differentiation-of-neural-precursor-cells-derived-from-human-embryonic-stem-cells
#11
Jin-Woo Park, Mi-Sun Lim, So Yeon Ji, Myung Soo Cho, Seong-Joo Park, Sung-Hee Han, Jin-Hee Kim
PURPOSE: Data from animal experiments suggest that exposure to general anesthetics in early life inhibits neurogenesis and causes long-term memory deficit. Considering short operating times and the popularity of sevoflurane in pediatric anesthesia, it is important to verify the effects of short-period exposure to sevoflurane on the developing brain. METHODS: We measured the effects of short-term exposure (2 h) to 3%, 6%, or 8% sevoflurane, the most commonly used anesthetic, on neural precursor cells derived from human embryonic stem cells, SNUhES32...
September 14, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28912615/why-the-moratorium-on-human-animal-chimera-research-should-not-be-lifted
#12
Alan Moy
The National Institutes of Health (NIH) announced its plans to lift its moratorium on funding research that involves injecting human embryonic stem cells into animal embryos, which would allow for the creation of part-human and part-animal organisms known as chimeras. The NIH allowed only one month to receive public comments in the midst of a presidential election campaign. Lifting the moratorium means that, for the first time, the federal government will begin spending taxpayer dollars on the creation and manipulation of new organisms that would blur the line between humans and animals...
August 2017: Linacre Quarterly
https://www.readbyqxmd.com/read/28912571/comparative-global-immune-related-gene-profiling-of-somatic-cells-human-pluripotent-stem-cells-and-their-derivatives-implication-for-human-lymphocyte-proliferation
#13
Chia-Eng Wu, Chen-Wei Yu, Kai-Wei Chang, Wen-Hsi Chou, Chen-Yu Lu, Elisa Ghelfi, Fang-Chun Wu, Pey-Shynan Jan, Mei-Chi Huang, Patrick Allard, Shau-Ping Lin, Hong-Nerng Ho, Hsin-Fu Chen
Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28905448/mzf1-and-gabp-cooperate-with-sox2-in-regulating-the-expression-of-yap1-in-cancer-cells
#14
Narendra Kumar Verma, Abhilash Gadi, Giulia Maurizi, Upal Basu Roy, Alka Mansukhani, Claudio Basilico
The transcription factor YAP1 is a major effector of the tumor suppressive Hippo signaling pathway and is also necessary to maintain pluripotency in embryonic stem cells. Elevated levels of YAP1 expression antagonize the tumor suppressive effects of the Hippo pathway, that normally represses YAP1 function. High YAP1 expression is observed in several types of human cancers and is particularly prominent in cancer stem cells. The stem cell transcription factor Sox2, which marks and maintains cancer stem cells in osteosarcomas, promotes YAP1 expression by binding to an intronic enhancer element and YAP1 expression is also crucial for the maintainance of osteosarcoma stem cells...
September 14, 2017: Stem Cells
https://www.readbyqxmd.com/read/28903495/rna-seq-of-human-neural-progenitor-cells-exposed-to-lead-pb-reveals-transcriptome-dynamics-splicing-alterations-and-disease-risk-associations
#15
Peng Jiang, Zhonggang Hou, Jennifer M Bolin, James A Thomson, Ron Stewart
Lead (Pb) is a well-known toxicant, especially for the developing nervous system, albeit the mechanism is largely unknown. In this study, we use time series RNA-seq to conduct a genome-wide survey of the transcriptome response of human embryonic stem cell-derived neural progenitor cells to lead treatment. Using a dynamic time warping algorithm coupled with statistical tests, we find that lead can either accelerate or decelerate the expression of specific genes during the time series. We further show that lead disrupts a neuron- and brain-specific splicing factor NOVA1 regulated splicing network...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28901192/neuronal-cell-sheets-of-cortical-motor-neuron-phenotype-derived-from-human-ipscs
#16
Noboru Suzuki, Nagisa Arimitsu, Jun Shimizu, Kenji Takai, Chieko Hirotsu, Yuji Ueda, Sueshige Wakisaka, Naruyoshi Fujiwara, Tomoko Suzuki
Transplantation of stem cells that differentiate into more mature neural cells brings about functional improvement in preclinical studies of stroke. Previous transplant approaches in the diseased brain utilized injection of the cells in a cell suspension. In addition, neural stem cells were preferentially used for grafting. However, these cells had no specific relationship to the damaged tissue of stroke and brain injury patients. The injection of cells in a suspension destroyed the cell-cell interactions that are suggested to be important for promoting functional integrity of cortical motor neurons...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28895148/critical-roles-of-hmagea2-in-induced-pluripotent-stem-cell-pluripotency-proliferation-and-differentiation
#17
Song Park, Yonghun Sung, Jain Jeong, Minjee Choi, Jinhee Lee, Wookbong Kwon, Soyoung Jang, Si Jun Park, Jae Young Kim, Sung Hyun Kim, Duhak Yoon, Zae Young Ryoo, Myoung Ok Kim
Induced pluripotent stem (iPS) cells are important for clinical application and stem cell research. Although human melanoma-associated antigen A2 (hMAGEA2) expression is known to affect differentiation in embryonic stem cells, its specific role in iPS cells remains unclear. To evaluate the function of hMAGEA2 and its characteristics in iPS cells, we produced hMAGEA2-overexpressing iPS cells from hMAGEA2-overexpressing transgenic mice. Although the iPS cells with overexpressed hMAGEA2 did not differ in morphology, their pluripotency, and self-renewal related genes (Nanog, Oct3/4, Sox2, and Stat3), expression level was significantly upregulated...
September 11, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28889951/pancreatic-%C3%AE-cell-regeneration-as-a-possible-therapy-for-diabetes
#18
REVIEW
Cristina Aguayo-Mazzucato, Susan Bonner-Weir
Diabetes is the result of having inadequate supply of functional insulin-producing β cells. Two possible approaches for replenishing the β cells are: (1) replacement by transplanting cadaveric islets or β cells derived from human embryonic stem cells/induced pluripotent stem cells and (2) induction of endogenous regeneration. This review focuses on endogenous regeneration, which can follow two pathways: enhanced replication of existing β cells and formation of new β cells from cells not expressing insulin, either by conversion from a differentiated cell type (transdifferentiation) or differentiation from progenitors (neogenesis)...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28889383/in-vitro-differentiation-and-propagation-of-urothelium-from-pluripotent-stem-cell-lines
#19
Stephanie L Osborn, Eric A Kurzrock
Bioengineering of bladder tissue, particularly for those patients who have advanced bladder disease, requires a source of urothelium that is healthy, capable of significant proliferation in vitro and immunologically tolerated upon transplant. As pluripotent stem cells have the potential to fulfill such criteria, they provide a critical cell source from which urothelium might be derived in vitro and used clinically. Herein, we describe the in vitro differentiation of urothelium from the H9 human embryonic stem cell (hESC) line through the definitive endoderm (DE) phase via selective culture techniques...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28889080/reprogramming-of-rabbit-induced-pluripotent-stem-cells-toward-epiblast-and-chimeric-competency-using-kr%C3%A3-ppel-like-factors
#20
Yann Tapponnier, Marielle Afanassieff, Irène Aksoy, Maxime Aubry, Anaïs Moulin, Lucas Medjani, Wilhelm Bouchereau, Chloé Mayère, Pierre Osteil, Jazmine Nurse-Francis, Ioannis Oikonomakos, Thierry Joly, Luc Jouneau, Catherine Archilla, Barbara Schmaltz-Panneau, Nathalie Peynot, Harmonie Barasc, Alain Pinton, Jérome Lecardonnel, Elen Gocza, Nathalie Beaujean, Véronique Duranthon, Pierre Savatier
Rabbit induced pluripotent stem cells (rbiPSCs) possess the characteristic features of primed pluripotency as defined in rodents and primates. In the present study, we reprogrammed rbiPSCs using human Krüppel-like factors (KLFs) 2 and 4 and cultured them in a medium supplemented with fetal calf serum and leukemia inhibitory factor. These cells (designated rbEKA) were propagated by enzymatic dissociation for at least 30 passages, during which they maintained a normal karyotype. This new culturing protocol resulted in transcriptional and epigenetic reconfiguration, as substantiated by the expression of transcription factors and the presence of histone modifications associated with naïve pluripotency...
September 5, 2017: Stem Cell Research
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