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https://www.readbyqxmd.com/read/29681544/dissecting-the-contributions-of-cooperating-gene-mutations-to-cancer-phenotypes-and-drug-responses-with-patient-derived-ipscs
#1
Chan-Jung Chang, Andriana G Kotini, Malgorzata Olszewska, Maria Georgomanoli, Julie Teruya-Feldstein, Henrik Sperber, Roberto Sanchez, Robert DeVita, Timothy J Martins, Omar Abdel-Wahab, Robert K Bradley, Eirini P Papapetrou
Connecting specific cancer genotypes with phenotypes and drug responses constitutes the central premise of precision oncology but is hindered by the genetic complexity and heterogeneity of primary cancer cells. Here, we use patient-derived induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing to dissect the individual contributions of two recurrent genetic lesions, the splicing factor SRSF2 P95L mutation and the chromosome 7q deletion, to the development of myeloid malignancy. Using a comprehensive panel of isogenic iPSCs-with none, one, or both genetic lesions-we characterize their relative phenotypic contributions and identify drug sensitivities specific to each one through a candidate drug approach and an unbiased large-scale small-molecule screen...
April 17, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29681539/x-chromosome-dosage-influences-dna-methylation-dynamics-during-reprogramming-to-mouse-ipscs
#2
Vincent Pasque, Rahul Karnik, Constantinos Chronis, Paula Petrella, Justin Langerman, Giancarlo Bonora, Juan Song, Lotte Vanheer, Anupama Sadhu Dimashkie, Alexander Meissner, Kathrin Plath
A dramatic difference in global DNA methylation between male and female cells characterizes mouse embryonic stem cells (ESCs), unlike somatic cells. We analyzed DNA methylation changes during reprogramming of male and female somatic cells and in resulting induced pluripotent stem cells (iPSCs). At an intermediate reprogramming stage, somatic and pluripotency enhancers are targeted for partial methylation and demethylation. Demethylation within pluripotency enhancers often occurs at ESC binding sites of pluripotency transcription factors...
April 14, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29681516/super-obese-patient-derived-ipsc-hypothalamic-neurons-exhibit-obesogenic-signatures-and-hormone-responses
#3
Uthra Rajamani, Andrew R Gross, Brooke E Hjelm, Adolfo Sequeira, Marquis P Vawter, Jie Tang, Vineela Gangalapudi, Yizhou Wang, Allen M Andres, Roberta A Gottlieb, Dhruv Sareen
The hypothalamus contains neurons that integrate hunger and satiety endocrine signals from the periphery and are implicated in the pathophysiology of obesity. The limited availability of human hypothalamic neurons hampers our understanding of obesity disease mechanisms. To address this, we generated human induced pluripotent stem cells (hiPSCs) from multiple normal body mass index (BMI; BMI ≤ 25) subjects and super-obese (OBS) donors (BMI ≥ 50) with polygenic coding variants in obesity-associated genes...
April 6, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29681444/high-cell-density-suppresses-bmp4-induced-differentiation-of-human-pluripotent-stem-cells-to-produce-macroscopic-spatial-patterning-in-a-unidirectional-perfusion-culture-chamber
#4
Shota Tashiro, Minh Nguyen Tuyet Le, Yuta Kusama, Eri Nakatani, Mika Suga, Miho K Furue, Taku Satoh, Shinji Sugiura, Toshiyuki Kanamori, Kiyoshi Ohnuma
Spatial pattern formation is a critical step in embryogenesis. Bone morphogenetic protein 4 (BMP4) and its inhibitors are major factors for the formation of spatial patterns during embryogenesis. However, spatial patterning of the human embryo is unclear because of ethical issues and isotropic culture environments resulting from conventional culture dishes. Here, we utilized human pluripotent stem cells (hiPSCs) and a simple anisotropic (unidirectional perfusion) culture chamber, which creates unidirectional conditions, to measure the cell community effect...
April 19, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29679845/establishment-of-stub1-chip-mutant-induced-pluripotent-stem-cells-ipscs-from-a-patient-with-gordon-holmes-syndrome-scar16
#5
Stefanie Schuster, Yvonne Schelling, Matthis Synofzik, Philip Höflinger, Ludger Schöls, Stefan Hauser
STUB1/CHIP is a central component of cellular protein homeostasis and interacts with key proteins involved in the pathogenesis of many neurodegenerative diseases. Here, we reprogrammed human skin fibroblasts from a 12-year-old male patient with recessive spinocerebellar ataxia type 16 (OMIM #615768), carrying compound heterozygous mutations (c.355C>T, c.880A>T) in STUB1. Genomic integrity of the iPSC line HIHCNi001-A without transgene integration and genomic aberration but with maintained disease-relevant mutations was proven by SNP array analysis and Sanger sequencing while pluripotency was verified by the expression of important pluripotency markers and the capacity to differentiate into cells of all three germ layers...
April 9, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29677590/generation-of-a-human-induced-pluripotent-stem-cell-line-from-urinary-cells-of-a-patient-with-primary-congenital-glaucoma-using-integration-free-sendai-technology
#6
Jingxue Zhang, Shen Wu, Man Hu, Qian Liu
We have generated a human induced pluripotent stem cell (iPSC) line derived from urinary cells of a 10years old patient with primary congenital glaucoma (PCG). The cells were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system and shown to have full differentiation potential. The line is available and registered in the human pluripotent stem cell registry as BIOi001-A.
April 9, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29675560/patterns-of-differential-gene-expression-in-a-cellular-model-of-human-islet-development-and-relationship-to-type-2-diabetes-predisposition
#7
Marta Perez-Alcantara, Christian Honoré, Agata Wesolowska-Andersen, Anna L Gloyn, Mark I McCarthy, Mattias Hansson, Nicola L Beer, Martijn van de Bunt
AIMS/HYPOTHESIS: Most type 2 diabetes-associated genetic variants identified via genome-wide association studies (GWASs) appear to act via the pancreatic islet. Observed defects in insulin secretion could result from an impact of these variants on islet development and/or the function of mature islets. Most functional studies have focused on the latter, given limitations regarding access to human fetal islet tissue. Capitalising upon advances in in vitro differentiation, we characterised the transcriptomes of human induced pluripotent stem cell (iPSC) lines differentiated along the pancreatic endocrine lineage, and explored the contribution of altered islet development to the pathogenesis of type 2 diabetes...
April 19, 2018: Diabetologia
https://www.readbyqxmd.com/read/29675520/designing-well-defined-photopolymerized-synthetic-matrices-for-three-dimensional-culture-and-differentiation-of-induced-pluripotent-stem-cells
#8
Elisa M Ovadia, David W Colby, April M Kloxin
Induced pluripotent stem cells (iPSCs) are of interest for the study of disease, where these cells can be derived from patients and have the potential to be differentiated into any cell type; however, three-dimensional (3D) culture and differentiation of iPSCs within well-defined synthetic matrices for these applications remains limited. Here, we aimed to establish synthetic cell-degradable hydrogels that allow precise presentation of specific biochemical cues for 3D culture of iPSCs with relevance for hypothesis testing and lineage-specific differentiation...
April 20, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29674172/generation-of-induced-pluripotent-stem-cells-from-a-patient-with-x-linked-juvenile-retinoschisis
#9
Chi-Hsien Peng, Kang-Chieh Huang, Huai-En Lu, Shih-Han Syu, Aliaksandr A Yarmishyn, Jyh-Feng Lu, Waradee Buddhakosai, Tai-Chi Lin, Chih-Chien Hsu, De-Kuang Hwang, Chia-Ning Shen, Shih-Jen Chen, Shih-Hwa Chiou
X-linked juvenile retinoschisis (XLRS) is a hereditary retinal dystrophy manifested as splitting of anatomical layers of retina. In this report, we generated a patient-specific induced pluripotent stem cell (iPSC) line, TVGH-iPSC-013-05, from the peripheral blood mononuclear cells of a male patient with XLRS by using the Sendai-virus delivery system. We believe that XLRS patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.
April 11, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29673930/amelioration-of-neurosensory-structure-and-function-in-animal-and-cellular-models-of-a-congenital-blindness
#10
Ji Yun Song, Puya Aravand, Sergei Nikonov, Lanfranco Leo, Arkady Lyubarsky, Jeannette L Bennicelli, Jieyan Pan, Zhangyong Wei, Ivan Shpylchak, Pamela Herrera, Daniel J Bennett, Nicoletta Commins, Albert M Maguire, Jennifer Pham, Anneke I den Hollander, Frans P M Cremers, Robert K Koenekoop, Ronald Roepman, Patsy Nishina, Shangzhen Zhou, Wei Pan, Gui-Shuang Ying, Tomas S Aleman, Jimmy de Melo, Ilan McNamara, Junwei Sun, Jason Mills, Jean Bennett
Most genetically distinct inherited retinal degenerations are primary photoreceptor degenerations. We selected a severe early onset form of Leber congenital amaurosis (LCA), caused by mutations in the gene LCA5, in order to test the efficacy of gene augmentation therapy for a ciliopathy. The LCA5-encoded protein, Lebercilin, is essential for the trafficking of proteins and vesicles to the photoreceptor outer segment. Using the AAV serotype AAV7m8 to deliver a human LCA5 cDNA into an Lca5 null mouse model of LCA5, we show partial rescue of retinal structure and visual function...
March 21, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29670862/organoid-and-enteroid-modeling-of-salmonella-infection
#11
REVIEW
Yuebang Yin, Daoguo Zhou
Salmonella are Gram-negative rod-shaped facultative anaerobic bacteria that are comprised of over 2,000 serovars. They cause gastroenteritis (salmonellosis) with headache, abdominal pain and diarrhea clinical symptoms. Salmonellosis brings a heavy burden for the public health in both developing and developed countries. Antibiotics are usually effective in treating the infected patients with severe gastroenteritis, although antibiotic resistance is on the rise. Understanding the molecular mechanisms of Salmonella infection is vital to combat the disease...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29669293/three-dimensional-human-ipsc-derived-artificial-skeletal-muscles-model-muscular-dystrophies-and-enable-multilineage-tissue-engineering
#12
Sara Martina Maffioletti, Shilpita Sarcar, Alexander B H Henderson, Ingra Mannhardt, Luca Pinton, Louise Anne Moyle, Heather Steele-Stallard, Ornella Cappellari, Kim E Wells, Giulia Ferrari, Jamie S Mitchell, Giulia E Tyzack, Vassilios N Kotiadis, Moustafa Khedr, Martina Ragazzi, Weixin Wang, Michael R Duchen, Rickie Patani, Peter S Zammit, Dominic J Wells, Thomas Eschenhagen, Francesco Saverio Tedesco
Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29666931/genome-editing-and-induced-pluripotent-stem-cell-technologies-for-personalized-study-of-cardiovascular-diseases
#13
REVIEW
Young Wook Chun, Matthew D Durbin, Charles C Hong
PURPOSE OF REVIEW: The goal of this review is to highlight the potential of induced pluripotent stem cell (iPSC)-based modeling as a tool for studying human cardiovascular diseases. We present some of the current cardiovascular disease models utilizing genome editing and patient-derived iPSCs. RECENT FINDINGS: The incorporation of genome-editing and iPSC technologies provides an innovative research platform, providing novel insight into human cardiovascular disease at molecular, cellular, and functional level...
April 17, 2018: Current Cardiology Reports
https://www.readbyqxmd.com/read/29666140/understanding-students-and-clinicians-experiences-of-informal-interprofessional-workplace-learning-an-australian-qualitative-study
#14
Charlotte E Rees, Paul Crampton, Fiona Kent, Ted Brown, Kerry Hood, Michelle Leech, Jennifer Newton, Michael Storr, Brett Williams
OBJECTIVES: While postgraduate studies have begun to shed light on informal interprofessional workplace learning, studies with preregistration learners have typically focused on formal and structured work-based learning. The current study investigated preregistration students' informal interprofessional workplace learning by exploring students' and clinicians' experiences of interprofessional student-clinician (IPSC) interactions. DESIGN: A qualitative interview study using narrative techniques was conducted...
April 17, 2018: BMJ Open
https://www.readbyqxmd.com/read/29665501/generation-of-an-integration-free-ipsc-line-cscri005-a-from-erythroid-progenitor-cells-of-a-healthy-indian-male-individual
#15
Kannan V Manian, Sumitha P Bharathan, Madhavi Maddali, Vivi M Srivastava, Alok Srivastava, Shaji Ramachandran Velayudhan
Reprogramming of somatic cells with higher genome integrity, and use of non-integrating gene delivery methods and xeno-free cell culture conditions aid in the generation of iPSCs which are more suitable for disease modelling and clinical applications. We describe here an iPSC line generated using such conditions, which expressed all the pluripotency markers, retained normal karyotype and exhibited the potential for tri-lineage differentiation, both in-vitro and in-vivo. This is the first iPSC line available from a healthy Indian individual for researchers...
April 3, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29663886/microrna-regulation-along-the-course-of-cellular-reprogramming-to-pluripotency
#16
M Ishtiaq, M Waseem, R Mehmood
Generation of patient-specific stem cells has been a long-held aim of many developmental biologists. Apart from providing a source for stem cell therapies, these cells have the potential to be utilized in a number of scenarios like disease modeling, drug screening and studying normal development. Various approaches have been used to reprogram terminally differentiated cells to a pluripotent state with varying efficiencies and limitations. The nuclear transfer had been the most successful method for reprogramming until recently...
April 15, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/29661116/crispr-cas9-targeted-deletion-of-polyglutamine-in-spinocerebellar-ataxia-type-3-derived-induced-pluripotent-stem-cells
#17
Shuming Ouyang, Yingjun Xie, Zeyu Xiong, Yi Yang, Yexing Xian, Zhanhui Ou, Bing Song, Yuchang Chen, Yuhuan Xie, Haoxian Li, Xiaofang Sun
Spinocerebellar ataxia type 3 (SCA3) is caused by an abnormal expansion of the CAG triplet in ATXN3, which translates into a polyglutamine (polyQ) tract within ataxin-3 (ATXN3) protein. Although the pathogenic mechanisms remain unclear, it is well established that expression of mutant forms of ATXN3 carrying an expanded polyQ domain are involved in SCA3 pathogenesis, and several strategies to suppress mutant ATXN3 have showed promising potential for SCA3 treatment. In this study, we described successful CRISPR/Cas9-mediated deletion of the expanded polyQ-encoding region of ATXN3 in induced pluripotent stem cells (iPSCs) derived from a SCA3 patient, and these patient-specific iPSCs retained pluripotency and neural differentiation following expanded polyQ deletion...
April 17, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29660608/generation-and-characterization-of-two-human-ipsc-lines-from-patients-with-methylmalonic-acidemia-cblb-type
#18
E Richard, S Brasil, A Briso-Montiano, E Alonso-Barroso, M E Gallardo, B Merinero, M Ugarte, L R Desviat, B Pérez
Two human induced pluripotent stem cell (iPSC) lines were generated from fibroblasts of two siblings with methylmalonic acidemia cblB type carrying mutations in the MMAB gene: c.287T➔C (p.Ile96Thr) and a splicing loss-of-function variant c.584G➔A affecting the last nucleotide of exon 7 in MMAB (p.Ser174Cysfs*23). Reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC were delivered using a non-integrative method based on the Sendai virus. Once established, iPSCs have shown full pluripotency, differentiation capacity and genetic stability...
April 5, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29660606/generation-of-induced-pluripotent-stem-cells-from-a-patient-with-best-dystrophy-carrying-11q12-3-best1-vmd2-mutation
#19
Chih-Chien Hsu, Huai-En Lu, Jen-Hua Chuang, Yu-Ling Ko, Yi-Ching Tsai, Hsiao-Yun Tai, Aliaksandr A Yarmishyn, De-Kuang Hwang, Mong-Lien Wang, Yi-Ping Yang, Shih-Jen Chen, Chi-Hsien Peng, Shih-Hwa Chiou, Tai-Chi Lin
Best disease (BD), also termed Best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and central visual loss. In this report, we generated an induced pluripotent stem cell (iPSC) line, TVGH-iPSC-012-04, from the peripheral blood mononuclear cells of a female patient with BD by using the Sendai virus delivery system. The resulting iPSCs retained the disease-causing DNA mutation, expressed pluripotent markers and could differentiate into three germ layers. We believe that BD patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease...
April 3, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29658608/ipsc%C3%A2-msc-inhibition-assessment-in-raw-264-7-cells-following-oxygen-and-glucose-deprivation-reveals-a-distinct-function-for-cardiopulmonary-resuscitation
#20
Yi Yu, Dongping Wang, Hui Li, Yujie Liu, Zhao Xiang, Junlin Wu, Xiaoli Jing
Hypoxia is a serious stress state. The nervous system is less tolerant to hypoxia, and cell death due to hypoxia is irreversible. With the incidence of cardiovascular disease gradually increasing, the sudden cardiac death rate is additionally increasing. Although cardiopulmonary resuscitation (CPR) is an important development, recovery is frequently poor. In a successful recovery population, ~40% of the population was in a vegetative state or subsequently succumbed to their condition, and ~20% had brain damage...
April 11, 2018: Molecular Medicine Reports
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