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https://www.readbyqxmd.com/read/28213969/highly-efficient-neural-conversion-of-human-pluripotent-stem-cells-in-adherent-and-animal-free-conditions
#1
Dunja Lukovic, Andrea Diez Lloret, Petra Stojkovic, Daniel Rodríguez-Martínez, Maria Amparo Perez Arago, Francisco Javier Rodriguez-Jimenez, Patricia González-Rodríguez, José López-Barneo, Eva Sykova, Pavla Jendelova, Jelena Kostic, Victoria Moreno-Manzano, Miodrag Stojkovic, Shomi S Bhattacharya, Slaven Erceg
Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, current hESCs and hiPSCs neural differentiation protocols require either animal factors or embryoid body formation, which decreases efficiency and yield, and strongly limits medical applications. Here we develop a simple, animal-free protocol for neural conversion of both hESCs and hiPSCs in adherent culture conditions...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28212312/genome-wide-prediction-of-dna-methylation-using-dna-composition-and-sequence-complexity-in-human
#2
Chengchao Wu, Shixin Yao, Xinghao Li, Chujia Chen, Xuehai Hu
DNA methylation plays a significant role in transcriptional regulation by repressing activity. Change of the DNA methylation level is an important factor affecting the expression of target genes and downstream phenotypes. Because current experimental technologies can only assay a small proportion of CpG sites in the human genome, it is urgent to develop reliable computational models for predicting genome-wide DNA methylation. Here, we proposed a novel algorithm that accurately extracted sequence complexity features (seven features) and developed a support-vector-machine-based prediction model with integration of the reported DNA composition features (trinucleotide frequency and GC content, 65 features) by utilizing the methylation profiles of embryonic stem cells in human...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28205557/experimental-study-of-the-biological-properties-of-human-embryonic-stem-cell-derived-retinal-progenitor-cells
#3
Jingzhi Shao, Peng-Yi Zhou, Guang-Hua Peng
Retinal degenerative diseases are among the leading causes of blindness worldwide, and cell replacement is considered as a promising therapeutic. However, the resources of seed cells are scarce. To further explore this type of therapy, we adopted a culture system that could harvest a substantial quantity of retinal progenitor cells (RPCs) from human embryonic stem cells (hESCs) within a relatively short period of time. Furthermore, we transplanted these RPCs into the subretinal spaces of Royal College of Surgeons (RCS) rats...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203608/modeling-fragile-x-syndrome-in-neurogenesis-an-unexpected-phenotype-and-a-novel-tool-for-future-therapies
#4
Barbara Bardoni, Maria Capovilla, Enzo Lalli
FMRP is an RNA-binding protein involved in synaptic translation. Its absence causes a form of intellectual disability, the Fragile X syndrome (FXS). Small neuroanatomical abnormalities, present both in human and mouse FMRP-deficient brains, suggest a subtle critical role of this protein in neurogenesis. Stable depletion of FMRP has been obtained in a mouse embryonic stem cell line Fmr1 (shFmr1 ES) that does not display morphological alterations, but an abnormal expression of a subset of genes mainly involved in neuronal differentiation and maturation...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28202491/organoid-technologies-meet-genome-engineering
#5
REVIEW
Jing Nie, Eri Hashino
Three-dimensional (3D) stem cell differentiation cultures recently emerged as a novel model system for investigating human embryonic development and disease progression in vitro, complementing existing animal and two-dimensional (2D) cell culture models. Organoids, the 3D self-organizing structures derived from pluripotent or somatic stem cells, can recapitulate many aspects of structural organization and functionality of their in vivo organ counterparts, thus holding great promise for biomedical research and translational applications...
February 15, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28199941/effect-directed-analysis-reveals-inhibition-of-zebrafish-uptake-transporter-oatp1d1-by-caulerpenyne-a-major-secondary-metabolite-from-the-invasive-marine-alga-caulerpa-taxifolia
#6
P Marić, M Ahel, I Senta, S Terzić, I Mikac, A Žuljević, T Smital
Caulerpa taxifolia is a marine alga of tropical and subtropical distribution and a well-known invasive species in several temperate regions. Its invasiveness mainly stems from the production of secondary metabolites, some of which are toxic or repellent substances. In this study we investigated the possible inhibitory effects of C. taxifolia secondary metabolites on the activity of two zebrafish (Danio rerio) uptake transporters that transport organic anions (Oatp1d1) and cations (Oct1). Both transporters were transiently transfected and overexpressed in human embryonic kidney HEK293T cells...
February 2, 2017: Chemosphere
https://www.readbyqxmd.com/read/28199886/construction-of-tissue-engineered-full-thickness-cornea-substitute-using-limbal-epithelial-cell-like-and-corneal-endothelial-cell-like-cells-derived-from-human-embryonic-stem-cells
#7
Canwei Zhang, Liqun Du, Peng Sun, Lin Shen, Jing Zhu, Kunpeng Pang, Xinyi Wu
The aim of this study was to construct a full-thickness artificial cornea substitute in vitro by coculturing limbal epithelial cell-like (LEC-like) cells and corneal endothelial cell-like (CEC-like) cells derived from human embryonic stem cells (hESCs) on APCM scaffold. A 400 μm thickness, 11 mm diameter APCM lamella containing Bowman's membrane was prepared as the scaffold using trephine and a special apparatus made by ourselves. LEC-like cells and CEC-like cells, derived from hESCs as our previously described, were cocultured on the scaffold using a special insert of 24-well plates that enabled seeding both sides of the scaffold...
February 6, 2017: Biomaterials
https://www.readbyqxmd.com/read/28199003/applications-of-induced-pluripotent-stem-cell-technologies-in-spinal-cord-injury
#8
REVIEW
Narihito Nagoshi, Hideyuki Okano
Numerous basic research studies have suggested the potential efficacy of neural precursor cell (NPC) transplantation in spinal cord injury (SCI). However, in most such studies the origin of the cells used was mainly fetal tissue or embryonic stem cells, both of which carry potential ethical concerns with respect to clinical use. The development of induced pluripotent stem cells (iPSCs) opened a new path toward regenerative medicine for SCI. iPSCs can be generated from somatic cells by induction of transcription factors, and induced to differentiate into NPCs with characteristics of cells of the central nervous system...
February 15, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28196199/survival-of-transplanted-human-embryonic-stem-cell-derived-retinal-pigment-epithelial-cells-in-a-human-recipient-for-22-months
#9
Sung Han Shim, Gwangil Kim, Dong Ryul Lee, Jeoung Eun Lee, Hee Jung Kwon, Won Kyung Song
No abstract text is available yet for this article.
February 9, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28195201/crispr-cas9-mediated-genome-editing-in-wild-derived-mice-generation-of-tamed-wild-derived-strains-by-mutation-of-the-a-nonagouti-gene
#10
Michiko Hirose, Ayumi Hasegawa, Keiji Mochida, Shogo Matoba, Yuki Hatanaka, Kimiko Inoue, Tatsuhiko Goto, Hideki Kaneda, Ikuko Yamada, Tamio Furuse, Kuniya Abe, Yoshihisa Uenoyama, Hiroko Tsukamura, Shigeharu Wakana, Arata Honda, Atsuo Ogura
Wild-derived mice have contributed to experimental mouse genetics by virtue of their genetic diversity, which may help increase the chance of identifying novel modifier genes responsible for specific phenotypes and diseases. However, gene targeting using wild-derived mice has been unsuccessful because of the unavailability of stable embryonic stem cells. Here, we report that CRISPR/Cas9-mediated gene targeting can be applied to the Japanese wild-derived MSM/Ms strain (Mus musculus molossinus). We targeted the nonagouti (a) gene encoding the agouti protein that is localized in hair and the brain...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195122/integrated-genomic-analyses-of-de-novo-pathways-underlying-atypical-meningiomas
#11
Akdes Serin Harmancı, Mark W Youngblood, Victoria E Clark, Süleyman Coşkun, Octavian Henegariu, Daniel Duran, E Zeynep Erson-Omay, Leon D Kaulen, Tong Ihn Lee, Brian J Abraham, Matthias Simon, Boris Krischek, Marco Timmer, Roland Goldbrunner, S Bülent Omay, Jacob Baranoski, Burçin Baran, Geneive Carrión-Grant, Hanwen Bai, Ketu Mishra-Gorur, Johannes Schramm, Jennifer Moliterno, Alexander O Vortmeyer, Kaya Bilgüvar, Katsuhito Yasuno, Richard A Young, Murat Günel
Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28194397/a-novel-human-tissue-engineered-3-d-functional-vascularized-cardiac-muscle-construct
#12
Mani T Valarmathi, John W Fuseler, Jeffrey M Davis, Robert L Price
Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28194183/regulation-of-stem-cell-properties-of-m%C3%A3-ller-glia-by-jak-stat-and-mapk-signaling-in-the-mammalian-retina
#13
REVIEW
Krista M Beach, Jianbo Wang, Deborah C Otteson
In humans and other mammals, the neural retina does not spontaneously regenerate, and damage to the retina that kills retinal neurons results in permanent blindness. In contrast to embryonic stem cells, induced pluripotent stem cells, and embryonic/fetal retinal stem cells, Müller glia offer an intrinsic cellular source for regenerative strategies in the retina. Müller glia are radial glial cells within the retina that maintain retinal homeostasis, buffer ion flux associated with phototransduction, and form the blood/retinal barrier within the retina proper...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28193876/vulnerability-of-primitive-human-placental-trophoblast-to-zika-virus
#14
Megan A Sheridan, Dinar Yunusov, Velmurugan Balaraman, Andrei P Alexenko, Shinichiro Yabe, Sergio Verjovski-Almeida, Danny J Schust, Alexander W Franz, Yoel Sadovsky, Toshihiko Ezashi, R Michael Roberts
Infection of pregnant women by Asian lineage strains of Zika virus (ZIKV) has been linked to brain abnormalities in their infants, yet it is uncertain when during pregnancy the human conceptus is most vulnerable to the virus. We have examined two models to study susceptibility of human placental trophoblast to ZIKV: cytotrophoblast and syncytiotrophoblast derived from placental villi at term and colonies of trophoblast differentiated from embryonic stem cells (ESC). The latter appear to be analogous to the primitive placenta formed during implantation...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193725/the-tgf-%C3%AE-family-in-the-reproductive-tract
#15
Diana Monsivais, Martin M Matzuk, Stephanie A Pangas
The transforming growth factor β (TGF-β) family has a profound impact on the reproductive function of various organisms. In this review, we discuss how highly conserved members of the TGF-β family influence the reproductive function across several species. We briefly discuss how TGF-β-related proteins balance germ-cell proliferation and differentiation as well as dauer entry and exit in Caenorhabditis elegans. In Drosophila melanogaster, TGF-β-related proteins maintain germ stem-cell identity and eggshell patterning...
February 13, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28192800/molecular-profiling-of-the-developing-lacrimal-gland-reveals-putative-role-of-notch-signaling-in-branching-morphogenesis
#16
Galina Dvoriantchikova, Wensi Tao, Steve Pappas, Gabriel Gaidosh, David T Tse, Dmitry Ivanov, Daniel Pelaez
Purpose: Although normal function of the lacrimal gland is essential for vision (and thus for human well-being), the lacrimal gland remains rather poorly understood at a molecular level. The purpose of this study was to identify new genes and signaling cascades involved in lacrimal gland development. Methods: To identify these genes, we used microarray analysis to compare the gene expression profiles of developing (embryonic) and adult lacrimal glands. Differential data were validated by quantitative RT-PCR, and several corresponding proteins were confirmed by immunohistochemistry and Western blot analysis...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28192743/behavior-of-leucine-rich-repeat-containing-g-protein-coupled-receptor-5-expressing-cells-in-the-reprogramming-process
#17
Yuko Arioka, Hiroyasu Ito, Akihiro Hirata, Katsunori Semi, Yasuhiro Yamada, Mitsuru Seishima
It remains unclear what cells are proper for the generation of induced pluripotent stem cells (iPSCs). Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is well known as a tissue stem cell and progenitor marker, both of which are reported to be sensitive to reprogramming. In the present study, we examined the reprogramming behavior of Lgr5-expressing cells (Lgr5+ cells). First, we compared reprogramming behavior using mouse Lgr5+ and Lgr5 negative (Lgr5-) hair follicles (HFs). The number of alkaline phosphatase staining-positive cells was lesser in a well of Lgr5+ HFs than in Lgr5- HFs; however, the ratio of Nanog+ SSEA1+ cells in the cell mixture derived from Lgr5+ HFs was much higher than that from Lgr5- HFs...
February 4, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28192470/differentiation-of-oligodendrocyte-progenitor-cells-from-dissociated-monolayer-and-feeder-free-cultured-pluripotent-stem-cells
#18
Tomoko Yamashita, Yuki Miyamoto, Yoshio Bando, Takashi Ono, Sakurako Kobayashi, Ayano Doi, Toshihiro Araki, Yosuke Kato, Takayuki Shirakawa, Yutaka Suzuki, Junji Yamauchi, Shigetaka Yoshida, Naoya Sato
Oligodendrocytes myelinate axons and form myelin sheaths in the central nervous system. The development of therapies for demyelinating diseases, including multiple sclerosis and leukodystrophies, is a challenge because the pathogenic mechanisms of disease remain poorly understood. Primate pluripotent stem cell-derived oligodendrocytes are expected to help elucidate the molecular pathogenesis of these diseases. Oligodendrocytes have been successfully differentiated from human pluripotent stem cells. However, it is challenging to prepare large amounts of oligodendrocytes over a short amount of time because of manipulation difficulties under conventional primate pluripotent stem cell culture methods...
2017: PloS One
https://www.readbyqxmd.com/read/28191782/preventing-pluripotent-cell-teratoma-in-regenerative-medicine-applied-to-hematology-disorders
#19
Aurelie Bedel, François Beliveau, Isabelle Lamrissi-Garcia, Benoit Rousseau, Isabelle Moranvillier, Benoit Rucheton, Veronique Guyonnet-Dupérat, Bruno Cardinaud, Hubert de Verneuil, François Moreau-Gaudry, Sandrine Dabernat
Iatrogenic tumorigenesis is a major limitation for the use of human induced pluripotent stem cells (hiPSCs) in hematology. The teratoma risk comes from the persistence of hiPSCs in differentiated cell populations. Our goal was to evaluate the best system to purge residual hiPSCs before graft without compromising hematopoietic repopulation capability. Teratoma risk after systemic injection of hiPSCs expressing the reporter gene luciferase was assessed for the first time. Teratoma formation in immune-deficient mice was tracked by in vivo bioimaging...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28191772/human-induced-pluripotent-cell-derived-sensory-neurons-for-fate-commitment-of-bone-marrow-derived-schwann-cells-implications-for-remyelination-therapy
#20
Sa Cai, Lei Han, Qiang Ao, Ying-Shing Chan, Daisy Kwok-Yan Shum
Strategies that exploit induced pluripotent stem cells (iPSCs) to derive neurons have relied on cocktails of cytokines and growth factors to bias cell-signaling events in the course of fate choice. These are often costly and inefficient, involving multiple steps. In this study, we took an alternative approach and selected 5 small-molecule inhibitors of key signaling pathways in an 8-day program to induce differentiation of human iPSCs into sensory neurons, reaching ≥80% yield in terms of marker proteins. Continuing culture in maintenance medium resulted in neuronal networks immunopositive for synaptic vesicle markers and vesicular glutamate transporters suggestive of excitatory neurotransmission...
February 2017: Stem Cells Translational Medicine
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