keyword
MENU ▼
Read by QxMD icon Read
search

Fragile X and stem cell

keyword
https://www.readbyqxmd.com/read/27900874/human-pluripotent-stem-cells-in-modeling-human-disorders-the-case-of-fragile-x-syndrome
#1
Dan Vershkov, Nissim Benvenisty
Human pluripotent stem cells (PSCs) generated from affected blastocysts or from patient-derived somatic cells are an emerging platform for disease modeling and drug discovery. Fragile X syndrome (FXS), the leading cause of inherited intellectual disability, was one of the first disorders modeled in both embryonic stem cells and induced PCSs and can serve as an exemplary case for the utilization of human PSCs in the study of human diseases. Over the past decade, FXS-PSCs have been used to address the fundamental questions regarding the pathophysiology of FXS...
November 30, 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27730449/integrated-transcriptome-analysis-of-human-ips-cells-derived-from-a-fragile-x-syndrome-patient-during-neuronal-differentiation
#2
Ping Lu, Xiaolong Chen, Yun Feng, Qiao Zeng, Cizhong Jiang, Xianmin Zhu, Guoping Fan, Zhigang Xue
Fragile X syndrome (FXS) patients carry the expansion of over 200 CGG repeats at the promoter of fragile X mental retardation 1 (FMR1), leading to decreased or absent expression of its encoded fragile X mental retardation protein (FMRP). However, the global transcriptional alteration by FMRP deficiency has not been well characterized at single nucleotide resolution, i.e., RNA-seq. Here, we performed in-vitro neuronal differentiation of human induced pluripotent stem (iPS) cells that were derived from fibroblasts of a FXS patient (FXS-iPSC)...
October 11, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27713816/cgg-repeat-dynamics-and-fmr1-gene-silencing-in-fragile-x-syndrome-stem-cells-and-stem-cell-derived-neurons
#3
Yifan Zhou, Daman Kumari, Nicholas Sciascia, Karen Usdin
BACKGROUND: Fragile X syndrome (FXS), a common cause of intellectual disability and autism, results from the expansion of a CGG-repeat tract in the 5' untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles, known as full mutation (FM) alleles, are epigenetically silenced in differentiated cells thus resulting in the loss of FMRP, a protein important for learning and memory. The timing of repeat expansion and FMR1 gene silencing is controversial. METHODS: We monitored the repeat size and methylation status of FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended period of time either as stem cells or differentiated into neurons...
2016: Molecular Autism
https://www.readbyqxmd.com/read/27711053/modeling-and-correction-of-structural-variations-in-patient-derived-ipscs-using-crispr-cas9
#4
Chul-Yong Park, Jin Jea Sung, Sang-Hwi Choi, Dongjin R Lee, In-Hyun Park, Dong-Wook Kim
Genome engineering technology using engineered nucleases has been rapidly developing, enabling the efficient correction of simple mutations. However, the precise correction of structural variations (SVs) such as large inversions remains limited. Here we describe a detailed procedure for the modeling or correction of large chromosomal rearrangements and short nucleotide repeat expansions using engineered nucleases in human induced pluripotent stem cells (hiPSCs) from a healthy donor and patients with SVs. This protocol includes the delivery of engineered nucleases with no donor template to hiPSCs, and genotyping and derivation/characterization of gene-manipulated hiPSC clones...
November 2016: Nature Protocols
https://www.readbyqxmd.com/read/27690107/modeling-fragile-x-syndrome-using-human-pluripotent-stem-cells
#5
Hagar Mor-Shaked, Rachel Eiges
Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from a loss-of-function mutation by a CGG repeat expansion at the 5' untranslated region of the X-linked fragile X mental retardation 1 (FMR1) gene. Expansion of the CGG repeats beyond 200 copies results in protein deficiency by leading to aberrant methylation of the FMR1 promoter and the switch from active to repressive histone modifications. Additionally, the CGGs become increasingly unstable, resulting in high degree of variation in expansion size between and within tissues of affected individuals...
2016: Genes
https://www.readbyqxmd.com/read/27664080/depletion-of-the-fragile-x-mental-retardation-protein-in-embryonic-stem-cells-alters-the-kinetics-of-neurogenesis
#6
Olfa Khalfallah, Marielle Jarjat, Laetitia Davidovic, Nicolas Nottet, Sandrine Cestèle, Massimo Mantegazza, Barbara Bardoni
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a leading cause of autism. FXS is due to the silencing of the Fragile X Mental Retardation Protein (FMRP), an RNA binding protein mainly involved in translational control, dendritic spine morphology and synaptic plasticity. Despite extensive studies, there is currently no cure for FXS. With the purpose to decipher the initial molecular events leading to this pathology, we developed a stem-cell-based disease model by knocking-down the expression of Fmr1 in mouse embryonic stem cells (ESCs)...
September 24, 2016: Stem Cells
https://www.readbyqxmd.com/read/27484867/magnetic-nanoparticle-based-upregulation-of-b-cell-lymphoma-2-enhances-bone-regeneration
#7
Elizabeth Brett, Elizabeth R Zielins, Anna Luan, Chin Chun Ooi, Siny Shailendra, David Atashroo, Siddarth Menon, Charles Blackshear, John Flacco, Natalina Quarto, Shan X Wang, Michael T Longaker, Derrick C Wan
: : Clinical translation of cell-based strategies for tissue regeneration remains challenging because survival of implanted cells within hostile, hypoxic wound environments is uncertain. Overexpression of B-cell lymphoma 2 (Bcl-2) has been shown to inhibit apoptosis in implanted cells. The present study describes an "off the shelf" prefabricated scaffold integrated with magnetic nanoparticles (MNPs) used to upregulate Bcl-2 expression in implanted adipose-derived stromal cells for bone regeneration...
August 2, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27422057/establishment-of-reporter-lines-for-detecting-fragile-x-mental-retardation-fmr1-gene-reactivation-in-human-neural-cells
#8
Meng Li, Huashan Zhao, Gene E Ananiev, Michael Musser, Kathryn H Ness, Dianne L Maglaque, Krishanu Saha, Anita Bhattacharyya, Xinyu Zhao
Human patient-derived induced pluripotent stem cells (hiPSCs) provide unique opportunities for disease modeling and drug development. However, adapting hiPSCs or their differentiated progenies to high throughput assays for phenotyping or drug screening has been challenging. Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and a major genetic cause of autism. FXS is caused by mutational trinucleotide expansion in the FMR1 gene leading to hypermethylation and gene silencing...
July 16, 2016: Stem Cells
https://www.readbyqxmd.com/read/27411166/metabotropic-glutamate-receptor-5-responses-dictate-differentiation-of-neural-progenitors-to-nmda-responsive-cells-in-fragile-x-syndrome
#9
Venkat Swaroop Achuta, Heli Grym, Noora Putkonen, Verna Louhivuori, Virve Kärkkäinen, Jari Koistinaho, Laurent Roybon, Maija L Castrén
Disrupted metabotropic glutamate receptor 5 (mGluR5) signaling is implicated in many neuropsychiatric disorders, including autism spectrum disorder, found in fragile X syndrome (FXS). Here we report that intracellular calcium responses to the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) are augmented, and calcium-dependent mGluR5-mediated mechanisms alter the differentiation of neural progenitors in neurospheres derived from human induced pluripotent FXS stem cells and the brains of mouse model of FXS...
July 13, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/27338628/the-long-non-coding-rnas-in-neurodegenerative-diseases-novel-mechanisms-of-pathogenesis
#10
Paola Riva, Antonia Ratti, Marco Venturin
BACKGROUND: Long-non-coding RNAs (lncRNAs), RNA molecules longer than 200 nucleotides, have been involved in several biological processes and in a growing number of diseases, controlling gene transcription, pre-mRNA processing, the transport of mature mRNAs to specific cellular compartments, the regulation of mRNA stability, protein translation and turnover. The fundamental role of lncRNAs in central nervous system (CNS) is becoming increasingly evident. LncRNAs are abundantly expressed in mammalian CNS in a specific spatio-temporal manner allowing a quick response to environmental/molecular changes...
June 22, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27242437/astrocyte-secreted-factors-selectively-alter-neural-stem-and-progenitor-cell-proliferation-in-the-fragile-x-mouse
#11
Mary Sourial, Laurie C Doering
UNLABELLED: An increasing body of evidence indicates that astrocytes contribute to the governance and fine tuning of stem and progenitor cell production during brain development. The effect of astrocyte function in cell production in neurodevelopmental disorders is unknown. We used the Neural Colony Forming Cell assay to determine the effect of astrocyte conditioned media (ACM) on the generation of neurospheres originating from either progenitor cells or functional stem cells in the knock out (KO) Fragile X mouse model...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27242433/immature-responses-to-gaba-in-fragile-x-neurons-derived-from-human-embryonic-stem-cells
#12
Michael Telias, Menahem Segal, Dalit Ben-Yosef
Fragile X Syndrome (FXS) is the most common form of inherited cognitive disability. However, functional deficiencies in FX neurons have been described so far almost exclusively in animal models. In a recent study we found several functional deficits in FX neurons differentiated in-vitro from human embryonic stem cells (hESCs), including their inability to fire repetitive action potentials, and their lack of synaptic activity. Here, we investigated the responses of such neurons to pulse application of the neurotransmitter GABA...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27122614/mdm2-inhibition-rescues-neurogenic-and-cognitive-deficits-in-a-mouse-model-of-fragile-x-syndrome
#13
Yue Li, Michael E Stockton, Ismat Bhuiyan, Brian E Eisinger, Yu Gao, Jessica L Miller, Anita Bhattacharyya, Xinyu Zhao
Fragile X syndrome, the most common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein (FMRP). However, the mechanism remains unclear, and effective treatment is lacking. We show that loss of FMRP leads to activation of adult mouse neural stem cells (NSCs) and a subsequent reduction in the production of neurons. We identified the ubiquitin ligase mouse double minute 2 homolog (MDM2) as a target of FMRP. FMRP regulates Mdm2 mRNA stability, and loss of FMRP resulted in elevated MDM2 mRNA and protein...
April 27, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27111774/modeling-the-autistic-cell-ipscs-recapitulate-developmental-principles-of-syndromic-and-nonsyndromic-asd
#14
REVIEW
Lihi Ben-Reuven, Orly Reiner
The opportunity to model autism spectrum disorders (ASD) through generation of patient-derived induced pluripotent stem cells (iPSCs) is currently an emerging topic. Wide-scale research of altered brain circuits in syndromic ASD, including Rett Syndrome, Fragile X Syndrome, Angelman's Syndrome and sporadic Schizophrenia, was made possible through animal models. However, possibly due to species differences, and to the possible contribution of epigenetics in the pathophysiology of these diseases, animal models fail to recapitulate many aspects of ASD...
June 2016: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/27047540/mouse-genetic-models-of-human-brain-disorders
#15
REVIEW
Celeste Leung, Zhengping Jia
Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/26772998/zfrp8-forms-a-complex-with-fragile-x-mental-retardation-protein-and-regulates-its-localization-and-function
#16
William Tan, Curtis Schauder, Tatyana Naryshkina, Svetlana Minakhina, Ruth Steward
Fragile-X syndrome is the most commonly inherited cause of autism and mental disabilities. The Fmr1 (Fragile-X Mental Retardation 1) gene is essential in humans and Drosophila for the maintenance of neural stem cells, and Fmr1 loss results in neurological and reproductive developmental defects in humans and flies. FMRP (Fragile-X Mental Retardation Protein) is a nucleo-cytoplasmic shuttling protein, involved in mRNA silencing and translational repression. Both Zfrp8 and Fmr1 have essential functions in the Drosophila ovary...
February 15, 2016: Developmental Biology
https://www.readbyqxmd.com/read/26722648/induced-pluripotent-stem-cells-for-modeling-neurological-disorders
#17
REVIEW
Fabiele B Russo, Fernanda R Cugola, Isabella R Fernandes, Graciela C Pignatari, Patricia C B Beltrão-Braga
Several diseases have been successfully modeled since the development of induced pluripotent stem cell (iPSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines...
December 24, 2015: World Journal of Transplantation
https://www.readbyqxmd.com/read/26663181/micrornas-and-fragile-x-syndrome
#18
Shi-Lung Lin
Fragile X syndrome (FXS) is one of the major causes for autism and mental retardation in humans. The etiology of FXS is linked to the expansion of the CGG trinucleotide repeats, r(CGG), suppressing the fragile X mental retardation 1 (FMR1) gene on the X chromosome, resulting in a loss of fragile X mental retardation protein (FMRP) expression, which is required for regulating normal neuronal connectivity and plasticity. Recent studies have further identified that microRNAs are involved in the mechanisms underlying FXS pathogenesis at three different developmental stages...
2015: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/26640241/human-pluripotent-stem-cell-models-of-fragile-x-syndrome
#19
REVIEW
Anita Bhattacharyya, Xinyu Zhao
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism. The causal mutation in FXS is a trinucleotide CGG repeat expansion in the FMR1 gene that leads to human specific epigenetic silencing and loss of Fragile X Mental Retardation Protein (FMRP) expression. Human pluripotent stem cells (PSCs), including human embryonic stem cells (ESCs) and particularly induced PSCs (iPSCs), offer a model system to reveal cellular and molecular events underlying human neuronal development and function in FXS...
June 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/26615955/rna-fish-for-detecting-expanded-repeats-in-human-diseases
#20
Martyna O Urbanek, Wlodzimierz J Krzyzosiak
RNA fluorescence in situ hybridization (FISH) is a widely used technique for detecting transcripts in fixed cells and tissues. Many variants of RNA FISH have been proposed to increase signal strength, resolution and target specificity. The current variants of this technique facilitate the detection of the subcellular localization of transcripts at a single molecule level. Among the applications of RNA FISH are studies on nuclear RNA foci in diseases resulting from the expansion of tri-, tetra-, penta- and hexanucleotide repeats present in different single genes...
April 1, 2016: Methods: a Companion to Methods in Enzymology
keyword
keyword
24797
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"