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https://www.readbyqxmd.com/read/29458125/pluripotent-stem-cells-for-uncovering-the-role-of-mitochondria-in-human-brain-function-and-dysfunction
#1
REVIEW
Annika Zink, Josef Priller, Alessandro Prigione
Mitochondrial dysfunctions are a known pathogenetic mechanism of a number of neurological and psychiatric disorders. At the same time, mutations in genes encoding for components of the mitochondrial respiratory chain cause mitochondrial diseases, which commonly exhibit neurological symptoms. Mitochondria are therefore critical for the functionality of the human nervous system. The importance of mitochondria stems from their key roles in cellular metabolism, calcium handling, redox and protein homeostasis, and overall cellular homeostasis through their dynamic network...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29456185/human-ips-derived-astroglia-from-a-stable-neural-precursor-state-show-improved-functionality-compared-with-conventional-astrocytic-models
#2
Anders Lundin, Louise Delsing, Maryam Clausen, Piero Ricchiuto, José Sanchez, Alan Sabirsh, Mei Ding, Jane Synnergren, Henrik Zetterberg, Gabriella Brolén, Ryan Hicks, Anna Herland, Anna Falk
In vivo studies of human brain cellular function face challenging ethical and practical difficulties. Animal models are typically used but display distinct cellular differences. One specific example is astrocytes, recently recognized for contribution to neurological diseases and a link to the genetic risk factor apolipoprotein E (APOE). Current astrocytic in vitro models are questioned for lack of biological characterization. Here, we report human induced pluripotent stem cell (hiPSC)-derived astroglia (NES-Astro) developed under defined conditions through long-term neuroepithelial-like stem (ltNES) cells...
February 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29456182/mitochondrial-dysfunctions-contribute-to-hypertrophic-cardiomyopathy-in-patient-ipsc-derived-cardiomyocytes-with-mt-rnr2-mutation
#3
Shishi Li, Huaye Pan, Chao Tan, Yaping Sun, Yanrui Song, Xuan Zhang, Wei Yang, Xuexiang Wang, Dan Li, Yu Dai, Qiang Ma, Chenming Xu, Xufen Zhu, Lijun Kang, Yong Fu, Xuejun Xu, Jing Shu, Naiming Zhou, Feng Han, Dajiang Qin, Wendong Huang, Zhong Liu, Qingfeng Yan
Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young individuals. A potential role of mtDNA mutations in HCM is known. However, the underlying molecular mechanisms linking mtDNA mutations to HCM remain poorly understood due to lack of cell and animal models. Here, we generated induced pluripotent stem cell-derived cardiomyocytes (HCM-iPSC-CMs) from human patients in a maternally inherited HCM family who carry the m.2336T>C mutation in the mitochondrial 16S rRNA gene (MT-RNR2)...
February 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29456180/ras-regulates-the-transition-from-naive-to-primed-pluripotent-stem-cells
#4
Anna Altshuler, Mila Verbuk, Swarnabh Bhattacharya, Ifat Abramovich, Roni Haklai, Jacob H Hanna, Yoel Kloog, Eyal Gottlieb, Ruby Shalom-Feuerstein
The transition from naive to primed state of pluripotent stem cells is hallmarked by epithelial-mesenchymal transition, metabolic switch from oxidative phosphorylation to aerobic glycolysis, and changes in the epigenetic landscape. Since these changes are also seen as putative hallmarks of neoplastic cell transformation, we hypothesized that oncogenic pathways may be involved in this process. We report that the activity of RAS is repressed in the naive state of mouse embryonic stem cells (ESCs) and that all three RAS isoforms are significantly activated upon early differentiation induced by LIF withdrawal, embryoid body formation, or transition to the primed state...
February 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29456178/hoxb4-promotes-hemogenic-endothelium-formation-without-perturbing-endothelial-cell-development
#5
Nadine Teichweyde, Lara Kasperidus, Sebastian Carotta, Valerie Kouskoff, Georges Lacaud, Peter A Horn, Stefan Heinrichs, Hannes Klump
Generation of hematopoietic stem cells (HSCs) from pluripotent stem cells, in vitro, holds great promise for regenerative therapies. Primarily, this has been achieved in mouse cells by overexpression of the homeotic selector protein HOXB4. The exact cellular stage at which HOXB4 promotes hematopoietic development, in vitro, is not yet known. However, its identification is a prerequisite to unambiguously identify the molecular circuits controlling hematopoiesis, since the activity of HOX proteins is highly cell and context dependent...
February 15, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29456164/pluripotent-stem-cells-as-a-source-of-osteoblasts-for-bone-tissue-regeneration
#6
Hui Zhu, Takaharu Kimura, Srilatha Swami, Joy Y Wu
Appropriate and abundant sources of bone-forming osteoblasts are essential for bone tissue engineering. Pluripotent stem cells can self-renew and thereby offer a potentially unlimited supply of osteoblasts, a significant advantage over other cell sources. We generated mouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) from transgenic mice expressing rat 2.3 kb type I collagen promoter-driven green fluorescent protein (Col2.3GFP), a reporter of the osteoblast lineage. We demonstrated that Col2...
February 5, 2018: Biomaterials
https://www.readbyqxmd.com/read/29456158/autologous-ipsc-based-vaccines-elicit-anti-tumor-responses-in-vivo
#7
Nigel G Kooreman, Youngkyun Kim, Patricia E de Almeida, Vittavat Termglinchan, Sebastian Diecke, Ning-Yi Shao, Tzu-Tang Wei, Hyoju Yi, Devaveena Dey, Raman Nelakanti, Thomas P Brouwer, David T Paik, Idit Sagiv-Barfi, Arnold Han, Paul H A Quax, Jaap F Hamming, Ronald Levy, Mark M Davis, Joseph C Wu
Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models...
February 8, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29456027/enhanced-chondrogenesis-differentiation-of-human-induced-pluripotent-stem-cells-by-microrna-140-and-transforming-growth-factor-beta-3-tgf%C3%AE-3
#8
Hossein Mahboudi, Masoud Soleimani, Seyed Ehsan Enderami, Mousa Kehtari, Abdolreza Ardeshirylajimi, Mohamad Eftekhary, Bahram Kazemi
Induced pluripotent stem cells (iPSCs) make an attractive source for regenerative medicine. The objective of our study was to establish a new method for differentiation of human iPSCs toward chondrocyte by overexpression of MicroRNA-140 (miR-140) and use of transforming growth factor beta 3 (TGFβ3) in high-cell density culture systems. We prepared vectors and then was used for recombinant Lenti virus production in HEK-293 cell. Transducted cells were selected and cultured in pellet culture system and were harvested after days 7, 14 and 21...
February 15, 2018: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/29455619/shaping-cell-fate-influence-of-topographical-substratum-properties-on-embryonic-stem-cells
#9
Sarita Kumari, Steven Vermeulen, Ben van der Veer, Aurélie Carlier, Jan de Boer, Deepa Subramanyam
Development of multicellular organisms is a highly orchestrated process, with cells responding to factors and features present in the extracellular milieu. Changes in the surrounding environment help decide the fate of cells at various stages of development. This review highlights recent research that details the effects of mechanical properties of the surrounding environment and extracellular matrix and the underlying molecular mechanisms that regulate the behaviour of embryonic stem cells. Here, we review the role of mechanical properties during embryogenesis and discuss the effect of engineered micro-topographies on embryonic stem cell pluripotency...
February 17, 2018: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29454965/detection-of-synchronized-burst-firing-in-cultured-human-induced-pluripotent-stem-cell-derived-neurons-using-a-4-step-method
#10
N Matsuda, A Odawara, H Kato, N Okuyama, R Yokoi, I Suzuki
Human induced pluripotent stem cell-derived neurons are promising for use in toxicity evaluations in nonclinical studies. The multi-electrode array (MEA) assay is used in such evaluation systems because it can measure the electrophysiological function of a neural network noninvasively and with high throughput. Synchronized burst firing (SBF) is the main analytic parameter of pharmacological effects in MEA data, but an accurate method for detecting SBFs has not been established. In this study, we present a 4-step method that accurately detects a target SBF confirmed by the researcher's interpretation of a raster plot...
February 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29454706/gata6-phosphorylation-by-erk1-2-propels-exit-from-pluripotency-and-commitment-to-primitive-endoderm
#11
Yue Meng, Robert Moore, Wensi Tao, Elizabeth R Smith, Jeffrey D Tse, Corrado Caslini, Xiang-Xi Xu
The transcription factor GATA6 and the Fgf/Ras/MAPK signaling pathway are essential for the development of the primitive endoderm (PrE), one of the two lineages derived from the pluripotent inner cell mass (ICM) of mammalian blastocysts. A mutant mouse line in which Gata6-coding exons are replaced with H2BGFP (histone H2B Green Fluorescence Protein fusion protein) was developed to monitor Gata6 promoter activity. In the Gata6-H2BGFP heterozygous blastocysts, the ICM cells that initially had uniform GFP fluorescence signal at E3...
February 15, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29454156/the-glun2b-subunit-represents-a-major-functional-determinant-of-nmda-receptors-in-human-induced-pluripotent-stem-cell-derived-cortical-neurons
#12
Ioana Neagoe, Chang Liu, Alexander Stumpf, Yanmei Lu, Dongping He, Ross Francis, Jun Chen, Paul Reynen, Moulay Hicham Alaoui-Ismaili, Hirokazu Fukui
Abnormal signaling pathways mediated by N-methyl-d-aspartate receptors (NMDARs) have been implicated in the pathogenesis of various CNS disorders and have been long considered as promising points of therapeutic intervention. However, few efforts have been previously described concerning evaluation of therapeutic modulators of NMDARs and their downstream pathways in human neurons with endogenous expression of NMDARs. In the present study, we assessed expression, functionality, and subunit composition of endogenous NMDARs in human induced pluripotent stem cell (hiPSC)-derived cortical neurons (iCell Neurons and iCell GlutaNeurons)...
February 8, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29453127/generation-of-d1-1-talen-isogenic-control-cell-line-from-dravet-syndrome-patient-ipscs-using-talen-mediated-editing-of-the-scn1a-gene
#13
Yasuyoshi Tanaka, Takefumi Sone, Norimichi Higurashi, Tetsushi Sakuma, Sadafumi Suzuki, Mitsuru Ishikawa, Takashi Yamamoto, Jun Mitsui, Hitomi Tsuji, Hideyuki Okano, Shinichi Hirose
Dravet syndrome (DS) is an infantile epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene encoding the α1 subunit of the voltage-gated sodium channel Nav 1.1. As an in vitro model of this disease, we previously generated an induced pluripotent stem cell (iPSC) line from a patient with DS carrying a c.4933C>T (p.R1645*) substitution in SCN1A. Here, we describe developing a genome-edited control cell line from this DS iPSC line by substituting the point mutation with the wild-type residue...
February 2, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29452453/-personalized-ophthalmology-induced-pluripotent-stem-cells-for-in-vitro-modelling-of-retinal-degenerative-diseases
#14
Caroline Brandl, Bernhard H F Weber
Today, the search for therapeutic options to treat retinal degeneration often relies on an in-depth understanding of the underlying pathological events. Alternatively, it is conceivable to search, in an undirected screening approach, for chemical compounds affecting disease outcome. For both approaches, there is an urgent need for in vitro and, ideally, in vivo disease models that adequately reflect the site of pathology. Currently available animal models possess limitations as they often develop only defined aspects of disease...
February 16, 2018: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/29452156/establishment-of-a-prkag2-cardiac-syndrome-disease-model-and-mechanism-study-using-human-induced-pluripotent-stem-cells
#15
Yongkun Zhan, Xiaolei Sun, Bin Li, Huanhuan Cai, Chen Xu, Qianqian Liang, Chao Lu, Ruizhe Qian, Sifeng Chen, Lianhua Yin, Wei Sheng, Guoying Huang, Aijun Sun, Junbo Ge, Ning Sun
PRKAG2 cardiac syndrome is a distinct form of human cardiomyopathy characterized by cardiac hypertrophy, ventricular pre-excitation and progressive cardiac conduction disorder. However, it remains unclear how mutations in the PRKAG2 gene give rise to such a complicated disease. To investigate the underlying molecular mechanisms, we generated disease-specific hiPSC-derived cardiomyocytes from two brothers both carrying a heterozygous missense mutation c.905G>A (R302Q) in the PRKAG2 gene and further corrected the R302Q mutation with CRISPR-Cas9 mediated genome editing...
February 13, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29451874/a-stochastic-and-dynamical-view-of-pluripotency-in-mouse-embryonic-stem-cells
#16
Yen Ting Lin, Peter G Hufton, Esther J Lee, Davit A Potoyan
Pluripotent embryonic stem cells are of paramount importance for biomedical sciences because of their innate ability for self-renewal and differentiation into all major cell lines. The fateful decision to exit or remain in the pluripotent state is regulated by complex genetic regulatory networks. The rapid growth of single-cell sequencing data has greatly stimulated applications of statistical and machine learning methods for inferring topologies of pluripotency regulating genetic networks. The inferred network topologies, however, often only encode Boolean information while remaining silent about the roles of dynamics and molecular stochasticity inherent in gene expression...
February 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29451340/therapeutic-neural-stem-cells-engineered-during-different-stages-of-reprogramming-reveal-varying-therapeutic-efficacies
#17
Deepak Bhere, Rajiv Kumar Khajuria, William T Hendriks, Antara Bandyopadhyay, Tugba Bagci-Onder, Khalid Shah
Stem cells are emerging as promising treatment strategies for several brain disorders and pathologies including brain tumors. In this study, we explored the potential of creating induced pluripotent stem cell (iPSC) derived therapeutic NSCs (ipNSC) by using either unmodified or gene-modified somatic cells and tested their fate and therapeutic efficacies in vitro and in vivo. We show that cells engineered in somatic state lose transgene-expression during the neural induction process, which is partially restored by HDAC inhibitor (i) treatment whereas cells engineered at the ipNSC state have sustained expression of transgenes...
February 16, 2018: Stem Cells
https://www.readbyqxmd.com/read/29451202/stem-cells-for-spinal-cord-injuries-bearing-translational-potential
#18
REVIEW
Kyriakos Dalamagkas, Magdalini Tsintou, Alexander M Seifalian
Spinal cord injury (SCI) is a highly debilitating neurological disease, which still lacks effective treatment strategies, causing significant financial burden and distress to the affected families. Nevertheless, nanotechnology and regenerative medicine strategies holding promise for the development of novel therapies that would reach from bench to bedside to serve the SCI patients. There has already been significant progress in the field of cell-based therapies, with the clinical application for SCI, currently in phase II of the clinical trial...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29449635/purkinje-cells-derived-from-tsc-patients-display-hypoexcitability-and-synaptic-deficits-associated-with-reduced-fmrp-levels-and-reversed-by-rapamycin
#19
Maria Sundberg, Ivan Tochitsky, David E Buchholz, Kellen Winden, Ville Kujala, Kush Kapur, Deniz Cataltepe, Daria Turner, Min-Joon Han, Clifford J Woolf, Mary E Hatten, Mustafa Sahin
Accumulating evidence suggests that cerebellar dysfunction early in life is associated with autism spectrum disorder (ASD), but the molecular mechanisms underlying the cerebellar deficits at the cellular level are unclear. Tuberous sclerosis complex (TSC) is a neurocutaneous disorder that often presents with ASD. Here, we developed a cerebellar Purkinje cell (PC) model of TSC with patient-derived human induced pluripotent stem cells (hiPSCs) to characterize the molecular mechanisms underlying cerebellar abnormalities in ASD and TSC...
February 15, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29449460/pfn2-and-gamt-as-common-molecular-determinants-of-axonal-charcot-marie-tooth-disease
#20
Manisha Juneja, Abdelkrim Azmi, Jonathan Baets, Andreas Roos, Matthew J Jennings, Paola Saveri, Chiara Pisciotta, Nathalie Bernard-Marissal, Bernard L Schneider, Catherine Verfaillie, Roman Chrast, Pavel Seeman, Angelika F Hahn, Peter de Jonghe, Stuart Maudsley, Rita Horvath, Davide Pareyson, Vincent Timmerman
BACKGROUND: Charcot-Marie-Tooth type 2 (CMT2) neuropathy is characterised by a vast clinical and genetic heterogeneity complicating its diagnosis and therapeutic intervention. Identification of molecular signatures that are common to multiple CMT2 subtypes can aid in developing therapeutic strategies and measuring disease outcomes. METHODS: A proteomics-based approach was performed on lymphoblasts from CMT2 patients genetically diagnosed with different gene mutations to identify differentially regulated proteins...
February 15, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
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