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https://www.readbyqxmd.com/read/28918520/derivation-of-human-induced-pluripotent-stem-cell-ipsc-lines-and-mechanism-of-pluripotency-historical-perspective-and-recent-advances
#1
REVIEW
Arvind Chhabra
Derivation of human embryonic stem cell (hES) lines in 1998 was not only a major technological breakthrough in the field of regenerative medicine; it also triggered a passionate debate about the ethical issues associated with the utilization of human embryos for derivation of hESC lines. Successful derivation of induced pluripotent stem cell (iPS) lines from human somatic cells with defined reprogramming factors by Shinya Yamanaka`s group in 2007 was another breakthrough that generated enormous excitement and hope for the development of donor-specific personalized cell replacement therapies (CRT) without the ethical dilemma associated with it...
September 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28918504/autism-spectrum-disorders-and-disease-modeling-using-stem-cells
#2
REVIEW
Anita Brito, Fabiele Baldino Russo, Alysson Renato Muotri, Patricia Cristina Baleeiro Beltrão-Braga
Autism spectrum disorders (ASD) represent a variety of disorders characterized as complex lifelong neurodevelopment disabilities, which may affect the ability of communication and socialization, including typical comportments like repetitive and stereotyped behavior. Other comorbidities are usually present, such as echolalia, hypotonia, intellectual disability and difficulties in processing figured speech. Furthermore, some ASD individuals may present certain abilities, such as eidetic memory, outstanding musical or painting talents and special mathematical skills, among others...
September 16, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28918057/one-step-piggybac-transposon-based-crispr-cas9-activation-of-multiple-genes
#3
Shenglan Li, Anqi Zhang, Haipeng Xue, Dali Li, Ying Liu
Neural cell fate is determined by a tightly controlled transcription regulatory network during development. The ability to manipulate the expression of multiple transcription factors simultaneously is required to delineate the complex picture of neural cell development. Because of the limited carrying capacity of the commonly used viral vectors, such as lentiviral or retroviral vectors, it is often challenging to perform perturbation experiments on multiple transcription factors. Here we have developed a piggyBac (PB) transposon-based CRISPR activation (CRISPRa) all-in-one system, which allows for simultaneous and stable endogenous transactivation of multiple transcription factors and long non-coding RNAs...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918022/antisense-oligonucleotides-reduce-rna-foci-in-spinocerebellar-ataxia-36-patient-ipscs
#4
Kosuke Matsuzono, Keiko Imamura, Nagahisa Murakami, Kayoko Tsukita, Takuya Yamamoto, Yuishin Izumi, Ryuji Kaji, Yasuyuki Ohta, Toru Yamashita, Koji Abe, Haruhisa Inoue
Spinocerebellar ataxia type 36 is a late-onset, slowly progressive cerebellar syndrome with motor neuron degeneration that is caused by expansions of a hexanucleotide repeat (GGCCTG) in the noncoding region of NOP56 gene, with a histopathological feature of RNA foci formation in postmortem tissues. Here, we report a cellular model using the spinocerebellar ataxia type 36 patient induced pluripotent stem cells (iPSCs). We generated iPSCs from spinocerebellar ataxia type 36 patients and differentiated them into neurons...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917552/crispr-correction-of-the-prkag2-gene-mutation-in-the-patient-s-ipsc-derived-cardiomyocytes-eliminates-the-electrophysiological-and-structural-abnormalities
#5
Ronen Ben Jehuda, Binyamin Eisen, Yuval Shemer, Lucy N Mekies, Agnes Szantai, Irina Reiter, Huanhuan Cui, Kaomei Guan, Shiraz Haron-Khun, Dov Freimark, Silke R Sperling, Mihaela Gherghiceanu, Michael Arad, Ofer Binah
BACKGROUND: Mutations in the PRKAG2 gene encoding the γ-subunit of adenosine monophosphate-kinase (AMPK) cause hypertrophic cardiomyopathy (HCM) and familial-Wolff-Parkinson-White syndrome (WPW). Patients carrying the R302Q mutation in PRKAG2 present sinus bradycardia, escape rhythms, ventricular pre-excitation, supraventricular tachycardia and atrioventricular block. This mutation affects AMPK activity and increases glycogen storage in cardiomyocytes. The link between glycogen storage, WPW, HCM and arrhythmias remains unknown...
September 13, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28917518/genome-stability-of-programmed-stem-cell-products
#6
REVIEW
Ulrich Martin
Inherited and acquired genomic abnormalities are known to cause genetic diseases and contribute to cancer formation. Recent studies demonstrated a substantial mutational load in mouse and human embryonic and induced pluripotent stem cells (ESCs and iPSCs). Single nucleotide variants, copy number variations, and larger chromosomal abnormalities may influence the differentiation capacity of pluripotent stem cells and the functionality of their derivatives in disease modelling and drug screening, and are considered a serious risk for cellular therapies based on ESC or iPSC derivatives...
September 13, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28917260/roles-of-sigma-1-receptors-on-mitochondrial-functions-relevant-to-neurodegenerative-diseases
#7
REVIEW
Tzu-Yu Weng, Shang-Yi Anne Tsai, Tsung-Ping Su
The sigma-1 receptor (Sig-1R) is a chaperone that resides mainly at the mitochondrion-associated endoplasmic reticulum (ER) membrane (called the MAMs) and acts as a dynamic pluripotent modulator in living systems. At the MAM, the Sig-1R is known to play a role in regulating the Ca(2+) signaling between ER and mitochondria and in maintaining the structural integrity of the MAM. The MAM serves as bridges between ER and mitochondria regulating multiple functions such as Ca(2+) transfer, energy exchange, lipid synthesis and transports, and protein folding that are pivotal to cell survival and defense...
September 16, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28916735/functional-screening-in-human-cardiac-organoids-reveals-a-metabolic-mechanism-for-cardiomyocyte-cell-cycle-arrest
#8
Richard J Mills, Drew M Titmarsh, Xaver Koenig, Benjamin L Parker, James G Ryall, Gregory A Quaife-Ryan, Holly K Voges, Mark P Hodson, Charles Ferguson, Lauren Drowley, Alleyn T Plowright, Elise J Needham, Qing-Dong Wang, Paul Gregorevic, Mei Xin, Walter G Thomas, Robert G Parton, Lars K Nielsen, Bradley S Launikonis, David E James, David A Elliott, Enzo R Porrello, James E Hudson
The mammalian heart undergoes maturation during postnatal life to meet the increased functional requirements of an adult. However, the key drivers of this process remain poorly defined. We are currently unable to recapitulate postnatal maturation in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), limiting their potential as a model system to discover regenerative therapeutics. Here, we provide a summary of our studies, where we developed a 96-well device for functional screening in human pluripotent stem cell-derived cardiac organoids (hCOs)...
September 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28916499/-re-programming-of-subtype-specific-cardiomyocytes
#9
Frauke Hausburg, Julia Jeannine Jung, Matti Hoch, Markus Wolfien, Arash Yavari, Christian Rimmbach, Robert David
Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential -a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterised by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production...
September 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28916494/transflammation-innate-immune-signaling-in-nuclear-reprogramming
#10
Shu Meng, Palas Chanda, Rajarajan A Thandavarayan, John P Cooke
Induction of pluripotency in somatic cells by retroviral overexpression of four transcription factors has revolutionized the field of stem cell biology and regenerative medicine. The efficient induction of pluripotency requires the activation of innate immune signaling in a process termed "transflammation" [1]. Specifically, the stimulation of pattern recognition receptors (PRRs) causes global alterations in the expression and activity of epigenetic modifiers to favor an open chromatin configuration. Activation of toll-like receptors (TLR) or RIG-1-like receptors (RLR) [2] trigger signaling cascades that result in NFκB or IRF-3 mediated changes in epigenetic plasticity that facilitate reprogramming...
September 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28916449/bio-scaffolds-in-organ-regeneration-clinical-potential-and-current-challenges
#11
REVIEW
S Yesmin, M B Paget, H E Murray, R Downing
Cadaveric organ transplantation represents the definitive treatment option for end-stage disease but is restricted by the shortage of clinically-viable donor organs. This limitation has, in part, driven current research efforts for in vitro generation of transplantable tissue surrogates. Recent advances in organ reconstruction have been facilitated by the re-purposing of decellularized whole organs to serve as three-dimensional bio-scaffolds. Notably, studies in rodents indicate that such scaffolds retain native extracellular matrix components that provide appropriate biochemical, mechanical and physical stimuli for successful tissue/organ reconstruction...
September 12, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28915407/differentiation-and-sarcomere-formation-in-skeletal-myocytes-directly-prepared-from-human-induced-pluripotent-stem-cells-using-a-sphere-based-culture
#12
Saowanee Jiwlawat, Eileen Lynch, Jennifer Glaser, Ivy Smit-Oistad, Jeremy Jeffrey, Jonathan M Van Dyke, Masatoshi Suzuki
Human induced-pluripotent stem cells (iPSCs) are a promising resource for propagation of myogenic progenitors. Our group recently reported a unique protocol for the derivation of myogenic progenitors directly (without genetic modification) from human pluripotent cells using free-floating spherical culture. Here we expand our previous efforts and attempt to determine how differentiation duration, culture surface coatings, and nutrient supplements in the medium influence progenitor differentiation and formation of skeletal myotubes containing sarcomeric structures...
August 1, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28915233/the-utility-of-stem-cells-in-pediatric-urinary-bladder-regeneration
#13
REVIEW
Philip M Iannaccone, Vasil Galat, Matthew I Bury, Yongchao C Ma, Arun K Sharma
Pediatric patients with a neurogenic urinary bladder caused by developmental abnormalities including spina bifida exhibit chronic urological problems. Surgical management in the form of enterocystoplasty is used to enlarge the bladder but is associated with significant clinical complications. Thus, alternative methods to enterocystoplasty have been explored through the incorporation of stem cells with tissue engineering strategies. Within the context of this review, we will examine the use of bone marrow stem cells and induced pluripotent stem cells (iPSCs) as they relate to bladder regeneration at the anatomic and molecular levels...
September 15, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28914051/chromosome-centric-human-proteome-project-allies-with-developmental-biology-a-case-study-of-the-role-of-y-chromosome-genes-in-organ-development
#14
Anna Meyfour, Paria Pooyan, Sara Pahlavan, Mostafa Rezaei-Tavirani, Hamid Gourabi, Hossein Baharvand, Ghasem Hosseini Salekdeh
One of the main goals of Chromosome-Centric Human Proteome Project is to identify protein evidence for missing proteins (MPs). Here, we present a case study of the role of Y chromosome genes in organ development and how to overcome the challenges facing MPs identification by employing human pluripotent stem cell differentiation into cells of different organs yielding unprecedented biological insight into adult silenced proteins. Y chromosome is a male-specific sex chromosome which escapes meiotic recombination...
September 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28913923/an-ipsc-patient-specific-model-of-cfh-y402h-polymorphism-displays-characteristic-features-of-amd-and-indicates-a-beneficial-role-for-uv-light-exposure
#15
Dean Hallam, Joseph Collin, Sanja Bojic, Valeria Chichagova, Adriana Buskin, Yaobo Xu, Lucia Lafage, Elsje G Otten, George Anyfantis, Carla Mellough, Stefan Przyborski, Sameer Alharthi, Viktor Korolchuk, Andrew Lotery, Gabriele Saretzki, Martin McKibbin, Lyle Armstrong, David Steel, David Kavanagh, Majlinda Lako
Age related macular degeneration (AMD) is the most common cause of blindness, accounting for 8.7% of all blindness globally. Vision loss is caused ultimately by apoptosis of the retinal pigment epithelium (RPE) and overlying photoreceptors. Treatments are evolving for the wet form of the disease, however these do not exist for the dry form. Complement factor H (CFH) polymorphism in exon 9 (Y402H) has shown a strong association with susceptibility to AMD resulting in complement activation, recruitment of phagocytes, retinal pigment epithelium (RPE) damage and visual decline...
September 15, 2017: Stem Cells
https://www.readbyqxmd.com/read/28912894/genetically-encoded-photoactuators-and-photosensors-for-characterization-and-manipulation-of-pluripotent-stem-cells
#16
REVIEW
Jordan E Pomeroy, Hung X Nguyen, Brenton D Hoffman, Nenad Bursac
Our knowledge of pluripotent stem cell biology has advanced considerably in the past four decades, but it has yet to deliver on the great promise of regenerative medicine. The slow progress can be mainly attributed to our incomplete understanding of the complex biologic processes regulating the dynamic developmental pathways from pluripotency to fully-differentiated states of functional somatic cells. Much of the difficulty arises from our lack of specific tools to query, or manipulate, the molecular scale circuitry on both single-cell and organismal levels...
2017: Theranostics
https://www.readbyqxmd.com/read/28912841/bioinformatics-method-identifies-potential-biomarkers-of-dilated-cardiomyopathy-in-a-human-induced-pluripotent-stem-cell-derived-cardiomyocyte-model
#17
Yu Zhuang, Yu-Jia Gong, Bei-Fen Zhong, Yi Zhou, Li Gong
Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy that account for the majority of heart failure cases. The present study aimed to reveal the underlying molecular mechanisms of DCM and provide potential biomarkers for detection of this condition. The public dataset of GSE35108 was downloaded, and 4 normal induced pluripotent stem cell (iPSC)-derived cardiomyocytes (N samples) and 4 DCM iPSC-derived cardiomyocytes (DCM samples) were utilized. Raw data were preprocessed, followed by identification of differentially expressed genes (DEGs) between N and DCM samples...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28912571/comparative-global-immune-related-gene-profiling-of-somatic-cells-human-pluripotent-stem-cells-and-their-derivatives-implication-for-human-lymphocyte-proliferation
#18
Chia-Eng Wu, Chen-Wei Yu, Kai-Wei Chang, Wen-Hsi Chou, Chen-Yu Lu, Elisa Ghelfi, Fang-Chun Wu, Pey-Shynan Jan, Mei-Chi Huang, Patrick Allard, Shau-Ping Lin, Hong-Nerng Ho, Hsin-Fu Chen
Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28912154/inhibition-of-p25-cdk5-attenuates-tauopathy-in-mouse-and-ipsc-models-of-frontotemporal-dementia
#19
Jinsoo Seo, Oleg Kritskiy, L Ashley Watson, Scarlett J Barker, Dilip Dey, Waseem K Raja, Yuan-Ta Lin, Tak Ko, Sukhee Cho, Jay Penney, M Catarina Silva, Steven D Sheridan, Diane Lucente, James F Gusella, Bradford C Dickerson, Stephen J Haggarty, Li-Huei Tsai
Increased p25, a proteolytic fragment of the regulatory subunit p35, is known to induce aberrant activity of cyclin-dependent kinase 5 (Cdk5), which is associated with neurodegenerative disorders including Alzheimer's disease (AD). Previously, we showed that replacing endogenous p35 with the non-cleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial AD mouse model. Here, to address the role of p25/Cdk5 in tauopathy, we generated double transgenic mice by crossing mice overexpressing mutant human tau (P301S) with Δp35KI mice...
September 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28911970/mesenchymal-stem-cells-alleviate-oxidative-stress-induced-mitochondrial-dysfunction-in-the-airways
#20
Xiang Li, Charalambos Michaeloudes, Yuelin Zhang, Coen H Wiegman, Ian M Adcock, Qizhou Lian, Judith C W Mak, Pankaj K Bhavsar, Kian Fan Chung
BACKGROUND: Oxidative stress-induced mitochondrial dysfunction may contribute to inflammation and remodeling in chronic obstructive pulmonary disease (COPD). Mesenchymal stem cells (MSCs) protect against lung damage in animal models of COPD. It is unknown whether these effects occur through attenuating mitochondrial dysfunction in airway cells. OBJECTIVE: To examine the effect of induced-pluripotent stem cell-derived MSCs (iPSC-MSCs) on oxidative stress-induce mitochondrial dysfunction in human airway smooth muscle cells (ASMCs) in vitro and in mouse lungs in vivo...
September 11, 2017: Journal of Allergy and Clinical Immunology
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