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https://www.readbyqxmd.com/read/28339300/genetic-manipulation-by-zinc-finger-nucleases-in-rat-induced-pluripotent-stem-cells
#1
Sheng Yang, Shufang Ding, Qianhua Xu, Xiong Li, Qiong Xiong
Induced pluripotent stem cells (iPSCs) have an extensive application in regenerative medicine, pharmaceutical discovery, and basic research. With the recent derivation of rat iPSCs, it is now feasible to apply genetic manipulation in this species. But such tools do not yet exist for many rat strains, especially for disease model rat. The Sprague Dawley (SD) rat is an inbred disease model for hypertension, nephropathy, pulmonary hypertension, depression, and alcohol consumption. In this study, the SD rat iPSCs were generated using lentiviral method...
March 24, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28336914/inhibition-of-serum-and-glucocorticoid-regulated-kinase-1-as-novel-therapy-for-cardiac-arrhythmia-disorders
#2
Vassilios J Bezzerides, Aifeng Zhang, Ling Xiao, Bridget Simonson, Santosh A Khedkar, Shiro Baba, Filomena Ottaviano, Stacey Lynch, Katherine Hessler, Alan C Rigby, David Milan, Saumya Das, Anthony Rosenzweig
Alterations in sodium flux (INa) play an important role in the pathogenesis of cardiac arrhythmias and may also contribute to the development of cardiomyopathies. We have recently demonstrated a critical role for the regulation of the voltage-gated sodium channel NaV1.5 in the heart by the serum and glucocorticoid regulated kinase-1 (SGK1). Activation of SGK1 in the heart causes a marked increase in both the peak and late sodium currents leading to prolongation of the action potential duration and an increased propensity to arrhythmia...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335666/control-of-dental-derived-induced-pluripotent-stem-cells-through-modified-surfaces-for-dental-application
#3
Hyunmin Choi, Kyu-Hyung Park, Ah-Reum Lee, Chin Hee Mun, Yong Dae Shin, Yong-Beom Park, Young-Bum Park
OBJECTIVE: The aim of this study is to investigate the behaviour of iPSc derived from dental stem cells in terms of initial adhesion, differentiation potential on differently surface-treated titanium disc. MATERIALS AND METHODS: iPSc derived from human gingival fibroblasts (hGFs) were established using 4-reprogramming factors transduction with Sendai virus. The hGF-iPSc established in this study exhibited the morphology and growth properties similar to human embryonic stem (ES) cells and expressed pluripotency makers...
March 23, 2017: Acta Odontologica Scandinavica
https://www.readbyqxmd.com/read/28335495/brain-derived-neurotrophic-factor-loaded-ps80-pbca-nanocarrier-for-in-vitro-neural-differentiation-of-mouse-induced-pluripotent-stem-cells
#4
Chiu-Yen Chung, Martin Hsiu-Chu Lin, I-Neng Lee, Tsong-Hai Lee, Ming-Hsueh Lee, Jen-Tsung Yang
Brain derived neurotrophic factor (BDNF) can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC) was constructed to deliver plasmid DNAs (pDNAs) containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF). The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs) to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting...
March 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334780/eif4a3-deficient-human-ipscs-and-mouse-models-demonstrate-neural-crest-defects-that-underlie-richieri-costa-pereira-syndrome
#5
Emily E Miller, Gerson S Kobayashi, Camila M Musso, Miranda Allen, Felipe A A Ishiy, Luiz C de Caires Junior, Ernesto S G Guimarães, Karina Griesi-Oliveira, Roseli M Zechi-Ceide, Antonio Richieri-Costa, Debora R Bertola, Maria Rita Passos-Bueno, Debra L Silver
Biallelic loss-of-function mutations in the RNA binding protein EIF4A3 cause Richieri-Costa-Pereira syndrome (RCPS), an autosomal recessive condition mainly characterized by craniofacial and limb malformations. However, the pathogenic cellular mechanisms responsible for this syndrome are entirely unknown. Here we used two complementary approaches, patient-derived induced pluripotent stem cells (iPSCs) and conditional Eif4a3 mouse models, to demonstrate that defective Neural Crest Cell (NCC) development explains RCPS craniofacial abnormalities...
March 2, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334554/rapid-establishment-of-the-european-bank-for-induced-pluripotent-stem-cells-ebisc-the-hot-start-experience
#6
Paul A De Sousa, Rachel Steeg, Elisabeth Wachter, Kevin Bruce, Jason King, Marieke Hoeve, Shalinee Khadun, George McConnachie, Julie Holder, Andreas Kurtz, Stefanie Seltmann, Johannes Dewender, Sascha Reimann, Glyn Stacey, Orla O'Shea, Charlotte Chapman, Lyn Healy, Heiko Zimmermann, Bryan Bolton, Trisha Rawat, Isobel Atkin, Anna Veiga, Bernd Kuebler, Blanca Miranda Serano, Tomo Saric, Jürgen Hescheler, Oliver Brüstle, Michael Peitz, Cornelia Thiele, Niels Geijsen, Bjørn Holst, Christian Clausen, Majlinda Lako, Lyle Armstrong, Shailesh K Gupta, Alexander J Kvist, Ryan Hicks, Anna Jonebring, Gabriella Brolén, Andreas Ebneth, Alfredo Cabrera-Socorro, Patrik Foerch, Martine Geraerts, Tina C Stummann, Shawn Harmon, Carol George, Ian Streeter, Laura Clarke, Helen Parkinson, Peter W Harrison, Adam Faulconbridge, Luca Cherubin, Tony Burdett, Cesar Trigueros, Minal J Patel, Christa Lucas, Barry Hardy, Rok Predan, Joh Dokler, Maja Brajnik, Oliver Keminer, Ole Pless, Philip Gribbon, Carsten Claussen, Annette Ringwald, Beate Kreisel, Aidan Courtney, Timothy E Allsopp
A fast track "Hot Start" process was implemented to launch the European Bank for Induced Pluripotent Stem Cells (EBiSC) to provide early release of a range of established control and disease linked human induced pluripotent stem cell (hiPSC) lines. Established practice amongst consortium members was surveyed to arrive at harmonised and publically accessible Standard Operations Procedures (SOPs) for tissue procurement, bio-sample tracking, iPSC expansion, cryopreservation, qualification and distribution to the research community...
March 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28333933/geometry-dependent-functional-changes-in-ipsc-derived-cardiomyocytes-probed-by-functional-imaging-and-rna-sequencing
#7
Christopher A Werley, Miao-Ping Chien, Jellert Gaublomme, Karthik Shekhar, Vincent Butty, B Alexander Yi, Joel M Kralj, William Bloxham, Laurie A Boyer, Aviv Regev, Adam E Cohen
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising platform for cardiac studies in vitro, and possibly for tissue repair in humans. However, hiPSC-CM cells tend to retain morphology, metabolism, patterns of gene expression, and electrophysiology similar to that of embryonic cardiomyocytes. We grew hiPSC-CM in patterned islands of different sizes and shapes, and measured the effect of island geometry on action potential waveform and calcium dynamics using optical recordings of voltage and calcium from 970 islands of different sizes...
2017: PloS One
https://www.readbyqxmd.com/read/28333144/aberrant-ipsc-derived-human-astrocytes-in-alzheimer-s-disease
#8
V C Jones, R Atkinson-Dell, A Verkhratsky, L Mohamet
The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed in vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development of a human iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form of AD (SAD). Our chemically defined and highly efficient model provides >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells (NPCs)...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28331164/immortalized-prairie-vole-derived-fibroblasts-vmf-k4dts-can-be-transformed-into-pluripotent-stem-cells-and-provide-a-useful-tool-with-which-to-determine-optimal-reprogramming-conditions
#9
Masafumi Katayama, Takashi Hirayama, Tohru Kiyono, Manabu Onuma, Tetsuya Tani, Satoru Takeda, Katsuhiko Nishimori, Tomokazu Fukuda
The cellular conditions required to establish induced pluripotent stem cells (iPSCs), such as the number of reprogramming factors and/or promoter selection, differ among species. The establishment of iPSCs derived from cells of previously unstudied species therefore requires the extensive optimization of programming conditions, including promoter selection and the optimal number of reprogramming factors, through a trial-and-error approach. While the four Yamanaka factors Oct3/4, Sox2, Klf4, and c-Myc are sufficient for iPSC establishment in mice, we reported previously that six reprogramming factors were necessary for the creation of iPSCs from primary prairie vole-derived cells...
March 23, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28330813/atp-binding-cassette-transporter-a1-deficiency-in-human-induced-pluripotent-stem-cell-derived-hepatocytes-abrogates-hdl-biogenesis-and-enhances-triglyceride-secretion
#10
Xin Bi, Evanthia E Pashos, Marina Cuchel, Nicholas N Lyssenko, Mayda Hernandez, Antonino Picataggi, James McParland, Wenli Yang, Ying Liu, Ruilan Yan, Christopher Yu, Stephanie L DerOhannessian, Michael C Phillips, Edward E Morrisey, Stephen A Duncan, Daniel J Rader
Despite the recognized role of the ATP-binding Cassette Transporter A1 (ABCA1) in high-density lipoprotein (HDL) metabolism, our understanding of ABCA1 deficiency in human hepatocytes is limited. To define the functional effects of human hepatocyte ABCA1 deficiency, we generated induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) from Tangier disease (TD) and matched control subjects. Control HLCs exhibited robust cholesterol efflux to apolipoprotein A-I (apoA-I) and formed nascent HDL particles...
March 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28329681/sirt6-promotes-dna-end-joining-in-ipscs-derived-from-old-mice
#11
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/28326305/implications-for-a-stem-cell-regenerative-medicine-based-approach-to-human-intervertebral-disk-degeneration
#12
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/28325300/one-step-biallelic-and-scarless-correction-of-a-%C3%AE-thalassemia-mutation-in-patient-specific-ipscs-without-drug-selection
#13
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/28322279/pluripotent-stem-cells-in-neuropsychiatric-disorders
#14
REVIEW
M A Soliman, F Aboharb, N Zeltner, L Studer
Neuropsychiatric disorders place an enormous medical burden on patients across all social and economic ranks. The current understanding of the molecular and cellular causes of neuropsychiatric disease remains limited, which leads to a lack of targeted therapies. Human-induced pluripotent stem cell (iPSC) technology offers a novel platform for modeling the genetic contribution to mental disorders and yields access to patient-specific cells for drug discovery and personalized medicine. Here, we review recent progress in using iPSC technology to model and potentially treat neuropsychiatric disorders by focusing on the most prevalent conditions in psychiatry, including depression, anxiety disorders, bipolar disorder and schizophrenia...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28319892/mitochondrial-hyperpolarization-in-ipsc-derived-neurons-from-patients-of-ftdp-17-with-10-16-mapt-mutation-leads-to-oxidative-stress-and-neurodegeneration
#15
Noemí Esteras, Jonathan D Rohrer, John Hardy, Selina Wray, Andrey Y Abramov
Tau protein inclusions are a frequent hallmark of a variety of neurodegenerative disorders. The 10+16 intronic mutation in MAPT gene, encoding tau, causes frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), by altering the splicing of the gene and inducing an increase in the production of 4R tau isoforms, which are more prone to aggregation. However, the molecular mechanisms linking increased 4R tau to neurodegeneration are not well understood. Here, we have used iPSC-derived neurons from patients of FTDP-17 carrying the 10+16 mutation to study the molecular mechanisms underlying neurodegeneration...
March 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28319609/developmental-alterations-in-huntington-s-disease-neural-cells-and-pharmacological-rescue-in-cells-and-mice
#16
(no author information available yet)
Neural cultures derived from Huntington's disease (HD) patient-derived induced pluripotent stem cells were used for 'omics' analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation...
March 20, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28318499/loss-of-function-mutations-in-lgi4-a-secreted-ligand-involved-in-schwann-cell-myelination-are-responsible-for-arthrogryposis-multiplex-congenita
#17
Shifeng Xue, Jérôme Maluenda, Florent Marguet, Mohammad Shboul, Loïc Quevarec, Carine Bonnard, Alvin Yu Jin Ng, Sumanty Tohari, Thong Teck Tan, Mung Kei Kong, Kristin G Monaghan, Megan T Cho, Carly E Siskind, Jacinda B Sampson, Carolina Tesi Rocha, Fawaz Alkazaleh, Marie Gonzales, Luc Rigonnot, Sandra Whalen, Marta Gut, Ivo Gut, Martine Bucourt, Byrappa Venkatesh, Annie Laquerrière, Bruno Reversade, Judith Melki
Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through genetic mapping of disease loci and whole-exome sequencing in four unrelated multiplex families presenting with severe AMC, we identified biallelic loss-of-function mutations in LGI4 (leucine-rich glioma-inactivated 4). LGI4 is a ligand secreted by Schwann cells that regulates peripheral nerve myelination via its cognate receptor ADAM22 expressed by neurons...
March 8, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28317340/production-of-pancreatic-progenitor-cells-from-human-induced-pluripotent-stem-cells-using-a-three-dimensional-suspension-bioreactor-system
#18
Yuichiro Mihara, Katsuhisa Matsuura, Yoshihiro Sakamoto, Teruo Okano, Norihiro Kokudo, Tatsuya Shimizu
Islet replacement is a promising strategy for the treatment of patients with type 1 diabetes and patients who have undergone total pancreatectomy. Recent progress in cellular reprogramming technology may allow the transplantation of a patient's own pancreatic cells. Although many studies have reported the differentiation of pancreatic progenitor cells from mouse and human pluripotent stem cells (PSCs), obtaining sufficient cell numbers for clinical applications remains problematic. Here, we describe the mass production of human pancreatic progenitor cells from human induced (i)PSCs using a three-dimensional suspension bioreactor system...
March 20, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28316107/applied-induced-pluripotent-stem-cells-in-combination-with-biomaterials-in-bone-tissue-engineering
#19
Abdolreza Ardeshirylajimi
Due to increasing of the orthopedic lesions and fractures in the world and limitation of current treatment methods, researchers and surgeons paid attention to the new treatment ways especially to tissue engineering and regenerative medicine. Innovation in stem cells and biomaterials accelerate during the last decade as two main important parts of the tissue engineering. Recently, induced pluripotent stem cells (iPSCs) introduced as cells with highly proliferation and differentiation potentials that hold great promising features for used in tissue engineering and regenerative medicine...
March 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28315308/target-specific-alterations-in-the-vip-inhibitory-drive-to-hippocampal-gabaergic-cells-after-status-epilepticus
#20
Linda Suzanne David, Lisa Topolnik
Status epilepticus (SE) is associated with complex reorganization of hippocampal circuits involving a significant loss of specific subtypes of GABAergic interneurons. While adaptive circuit plasticity may increase the chances for recruitment of surviving interneurons, the underlying mechanisms remain largely unknown. We studied the alterations in the inhibitory tone received by the hippocampal CA1 oriens/alveus (O/A) interneurons from the vasoactive intestinal peptide (VIP)- and calretinin (CR)-expressing interneurons using the pilocarpine-induced status epilepticus (SE) model of epilepsy...
March 15, 2017: Experimental Neurology
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