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human Embryonic stem cell

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https://www.readbyqxmd.com/read/28938535/accurate-primary-germ-cell-cancer-diagnosis-using-serum-based-microrna-detection-amptsmir-test
#1
Ton van Agthoven, Leendert H J Looijenga
Multiple studies, including various methods and overall limited numbers of mostly heterogeneous cases, indicate that the level of embryonic stem cell microRNAs (miRs) (e.g. 371a-3p, 372-3p, 373-3p, and 367-3p) are increased in serum at primary diagnosis of almost all testicular germ cell cancer (TGCC). Here we determine the status of three of these miRs in serum samples of 250 TGCC patients, collected at time of primary diagnosis, compared with 60 non-TGCC patients and 104 male healthy donors. The levels of miRs were measured by the robust ampTSmiR test, including magnetic bead-based miR isolation and target specific pre-amplification followed by real-time quantitative PCR (RT-qPCR) detection...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938435/the-role-of-sequential-bmp-signaling-in-directing-human-embryonic-stem-cells-to-bipotential-gonadal-cells
#2
Kirsi Sepponen, Karolina Lundin, Katri Knuus, Pia Väyrynen, Taneli Raivio, Juha S Tapanainen, Timo Tuuri
Context: Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but due to a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed. Objective: Our objective was to establish an in vitro method for studying differentiation of bipotential gonadal progenitors using human embryonic stem cells (hESCs), and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation...
August 29, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28933914/comparison-of-cellular-transforming-activity-of-oct4-nanog-and-sox2-in-immortalized-astrocytes
#3
Sunyoung Seo, Hee-Young Jeon, Hyunggee Kim
Embryonic stem cell factors-OCT4, NANOG, and SOX2-contribute to the maintenance of stem cell properties and malignant progression in various cancers, including glioblastoma. Although functional roles of each of these genes are well documented in stem cell and cancer biology, no study has directly compared their cellular transforming activity under same experimental conditions. In this study, we compared the cellular transforming activity of OCT4, NANOG, and SOX2 using human immortalized astrocytes cultured under serum-free stem cell culture conditions...
September 21, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28933288/stem-cell-differentiation-stage-factors-and-their-role-in-triggering-symmetry-breaking-processes-during-cancer-development-a-quantum-field-theory-model-for-reprogramming-cancer-cells-to-healthy-phenotypes
#4
Pier Mario Biava, Fabio Burigana, Roberto Germano, Philip Kurian, Claudio Verzegnassi, Giuseppe Vitiello
A long history of research has pursued the use of embryonic factors isolated during cell differentiation processes for the express purpose of transforming cancer cells back to healthy phenotypes. Recent results have clarified that the substances present at different stages of cell differentiation-which we call stem cell differentiation stage factors (SCDSFs)-are proteins with low molecular weight and nucleic acids that regulate genomic expression. The present review summarizes how these substances, taken at different stages of cellular maturation, are able to retard proliferation of many human tumor cell lines and thereby reprogram cancer cells to healthy phenotypes...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28933218/effects-of-human-es-derived-neural-stem-cell-transplantation-and-kindling-in-a-rat-model-of-traumatic-brain-injury
#5
Stefania Beretta, Kelly M Cunningham, Daniel L Haus, Eric M Gold, Harvey Perez, Luci López-Velázquez, Brian J Cummings
Traumatic brain injury (TBI) is one of the leading causes of death and disability in the population worldwide, with a broad spectrum of symptoms and disabilities. Posttraumatic hyperexcitability is one of the most common neurological disorders that affect people after a head injury. A reliable animal model of posttraumatic hyperexcitability induced by TBI which allows one to test effective treatment strategies is yet to be developed. To address these issues, in the present study, we tested human embryonic stem cell-derived neural stem cell (NSC) transplantation in an animal model of posttraumatic hyperexcitability in which the brain injury was produced in one hemisphere of immunodeficient athymic nude rats by controlled cortical impact, and spontaneous seizures were produced by repeated electrical stimulation (kindling) in the contralateral hemisphere...
July 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28931519/beta-cell-replacement-in-mice-using-human-type-1-diabetes-nuclear-transfer-embryonic-stem-cells
#6
Lina Sui, Nichole Danzl, Sean R Campbell, Ryan Viola, Damian Williams, Yuan Xing, Yong Wang, Neil Phillips, Greg Poffenberger, Bjarki Johannesson, Jose Oberholzer, Alvin C Powers, Rudolph L Leibel, Xiaojuan Chen, Megan Sykes, Dieter Egli
Beta cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ES) derived from a type 1 diabetes patient to differentiate into beta cells, and provide a source of autologous islets for cell replacement. NT-ES cells differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature beta cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells...
September 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28928909/transplanting-embryonic-stem-cells-onto-damaged-human-corneal-endothelium
#7
Charles Hanson, Arsaell Arnarsson, Thorir Hardarson, Ann Lindgård, Mandana Daneshvarnaeini, Catarina Ellerström, Anita Bruun, Ulf Stenevi
AIM: To investigate whether human embryonic stem cells (hESCs) could be made to attach, grow and differentiate on a human Descemet's membrane (DM). METHODS: Spontaneously differentiated hESCs were transferred onto a human corneal button with the endothelial layer removed using ocular sticks. The cells were cultured on a DM for up to 15 d. The genetically engineered hESC line expressed green fluorescent protein, which facilitated identification during the culture experiments, tissue preparation, and analysis...
August 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28928383/human-stem-cells-alter-the-invasive-properties-of-somatic-cells-via-paracrine-activation-of-mtorc1
#8
Margit Rosner, Ha Thi Thanh Pham, Richard Moriggl, Markus Hengstschläger
Controlled invasion is essential during many physiological processes, whereas its deregulation is a hallmark of cancer. Here we demonstrate that embryonic, induced pluripotent and amniotic fluid stem cells share the property to induce the invasion of primary somatic cells of various origins through insulin-like growth factor I (IGF-I)- or II (IGF-II)-mediated paracrine activation of mechanistic target of rapamycin complex 1 (mTORC1). We propose a model in which downstream of mTORC1 this stem cell-induced invasion is mediated by hypoxia-inducible factor 1-alpha (HIF-1α)-regulated matrix metalloproteinases...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928204/bone-morphogenetic-protein-and-retinoic-acid-synergistically-specify-female-germ-cell-fate-in-mice
#9
Hidetaka Miyauchi, Hiroshi Ohta, So Nagaoka, Fumio Nakaki, Kotaro Sasaki, Katsuhiko Hayashi, Yukihiro Yabuta, Tomonori Nakamura, Takuya Yamamoto, Mitinori Saitou
The mechanism for sex determination in mammalian germ cells remains unclear. Here, we reconstitute the female sex determination in mouse germ cells in vitro under a defined condition without the use of gonadal somatic cells. We show that retinoic acid (RA) and its key effector, STRA8, are not sufficient to induce the female germ-cell fate. In contrast, bone morphogenetic protein (BMP) and RA synergistically induce primordial germ cells (PGCs)/PGC-like cells (PGCLCs) derived from embryonic stem cells (ESCs) into fetal primary oocytes...
September 19, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28927307/biological-therapy-for-non-obstructive-azoospermia
#10
Sarah C Vij, Edmund Sabanegh, Ashok Agarwal
Most male patients with non-obstructive azoospermia (NOA) have no therapeutic options outside of assisted reproductive techniques to conceive a biological child. If mature sperm cannot be obtained from the testes, these patients must rely on options of donor sperm or adoption. Several techniques are in the experimental stage to provide this patient population alternatives for conceiving. Areas covered: This review discusses three of the experimental techniques for restoring fertility in men with NOA: spermatogonial stem cell transplantation, the use of adult and embryonic stem cells to develop mature gametes and gene therapy...
September 19, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28925362/generation-of-a-klf15-homozygous-knockout-human-embryonic-stem-cell-line-using-paired-crispr-cas9n-and-human-cardiomyocytes-derivation
#11
Claudia Noack, Luis Peter Haupt, Wolfram-Hubertus Zimmermann, Katrin Streckfuss-Bömeke, Laura Cecilia Zelarayán
Krueppel-like factor 15 (KLF15) is abundantly expressed in liver, kidney, and muscle, including myocardium. In the adult heart KLF15 is important to maintain homeostasis and to repress hypertrophic remodeling. We generated a homozygous hESC KLF15 knockout (KO) line using paired CRISPR/Cas9n. KLF15-KO cells maintained full pluripotency and differentiation potential as well as genomic integrity. We demonstrated that KLF15-KO cells can be differentiated into morphologically normal cardiomyocytes turning them into a valuable tool for studying human KLF15-mediated mechanisms resulting in human cardiac dysfunction...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925361/generation-of-a-homozygous-gba-deletion-human-embryonic-stem-cell-line
#12
Anna Lisa Gündner, Claas Aiko Meyer, Stefan Aigner, Klaus Christensen, Christoph Patsch, Ravi Jagasia, Karlheinz Baumann, Mark Burcin
We describe the generation of a biallelic GBA deletion human embryonic stem cell line using zinc finger nuclease-mediated gene targeting. The homozygous targeting of exon 4 of the GBA locus leads to a complete loss of glucocerebrosidase (GCase) protein expression.
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28924044/nuclear-insulin-like-growth-factor-1-receptor-phosphorylates-proliferating-cell-nuclear-antigen-and-rescues-stalled-replication-forks-after-dna-damage
#13
Ahmed Waraky, Yingbo Lin, Dudi Warsito, Felix Haglund, Eiman Aleem, Olle Larsson
We have previously shown that the insulin like growth factor 1 receptor (IGF1R) translocates to the cell nucleus, where it binds to enhancer like regions and increases gene transcription. Further studies have demonstrated that nuclear IGF1R (nIGF1R) physically and functionally interacts with some nuclear proteins, i.e. the lymphoid enhancer binding factor 1 (Lef1), histone H3, and Brahma related gene 1 proteins. In the present study, we identified the proliferating cell nuclear antigen (PCNA) as a nIGF1R binding partner...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28923841/a-novel-notch-yap-circuit-drives-stemness-and-tumorigenesis-in-embryonal-rhabdomyosarcoma
#14
Katherine K Slemmons, Lisa E S Crose, Stefan Riedel, Manuela Sushnitha, Brian C Belyea, Corinne M Linardic
Rhabdomyosarcoma (RMS), a cancer characterized by skeletal muscle features, is the most common soft tissue sarcoma of childhood. While low and intermediate-risk groups have seen improved outcomes, high-risk patients still face a 5-year survival of <30%, a statistic that has not changed in over 40 years. Understanding the biologic underpinnings of RMS is critical. The developmental pathways of Notch and YAP have been identified as potent but independent oncogenic signals that support the embryonal variant of RMS (eRMS)...
September 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28923074/expression-of-concern-to-therapeutic-potential-of-human-embryonic-stem-cell-transplantation-in-patients-with-cerebral-palsy
#15
Geeta Shroff, Anupama Gupta, Jitender Kumar Barthakur
The Editor-in-Chief of the Journal of Translational Medicine is issuing an editorial expression of concern to alert readers that concerns have been raised regarding the ethics of this study [1] and the potential association of the risk of teratoma formation with the transplantation of embryonic stem cells. Appropriate editorial action will be taken once this has been fully investigated. The authors disagree with this notice.
September 18, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28922739/o-glcnac-transferase-regulates-transcriptional-activity-of-human-oct4
#16
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
#17
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
#18
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
#19
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
#20
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
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