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neuron direct reprogramming

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https://www.readbyqxmd.com/read/28480968/the-influence-of-raav2-mediated-sox2-delivery-into-neonatal-and-adult-human-rpe-cells-a-comparative-study
#1
Razie Ezati, Azadeh Etemadzadeh, Zahra-Soheila Soheili, Shahram Samiei, Ehsan Ranaei Pirmardan, Malihe Davari, Hoda Shams Najafabadi
Cell replacement is a promising therapy for degenerative diseases like age-related macular degeneration (AMD). Since the human retina lacks regeneration capacity, much attention has been directed towards persuading for cells that can differentiate into retinal neurons. In this report we have investigated reprogramming of the human RPE cells and concerned the effect of donor age on the cellular fate as a critical determinant in reprograming competence. We evaluated the effect of SOX2 over-expression in human neonatal and adult RPE cells in cultures...
May 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28430167/induced-pluripotent-stem-cell-modeling-of-gaucher-s-disease-what-have-we-learned
#2
REVIEW
Dino Matias Santos, Gustavo Tiscornia
Gaucher's disease (GD) is the most frequently inherited lysosomal storage disease, presenting both visceral and neurologic symptoms. Mutations in acid β-glucocerebrosidase disrupt the sphingolipid catabolic pathway promoting glucosylceramide (GlcCer) accumulation in lysosomes. Current treatment options are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). However, neither of these approaches is effective in treating the neurological aspect of the disease. The use of small pharmacological compounds that act as molecular chaperones is a promising approach that is still experimental...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28398344/induction-of-functional-dopamine-neurons-from-human-astrocytes-in-vitro-and-mouse-astrocytes-in-a-parkinson-s-disease-model
#3
Pia Rivetti di Val Cervo, Roman A Romanov, Giada Spigolon, Débora Masini, Elisa Martín-Montañez, Enrique M Toledo, Gioele La Manno, Michael Feyder, Christian Pifl, Yi-Han Ng, Sara Padrell Sánchez, Sten Linnarsson, Marius Wernig, Tibor Harkany, Gilberto Fisone, Ernest Arenas
Cell replacement therapies for neurodegenerative disease have focused on transplantation of the cell types affected by the pathological process. Here we describe an alternative strategy for Parkinson's disease in which dopamine neurons are generated by direct conversion of astrocytes. Using three transcription factors, NEUROD1, ASCL1 and LMX1A, and the microRNA miR218, collectively designated NeAL218, we reprogram human astrocytes in vitro, and mouse astrocytes in vivo, into induced dopamine neurons (iDANs)...
May 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28379941/myt1l-safeguards-neuronal-identity-by-actively-repressing-many-non-neuronal-fates
#4
Moritz Mall, Michael S Kareta, Soham Chanda, Henrik Ahlenius, Nicholas Perotti, Bo Zhou, Sarah D Grieder, Xuecai Ge, Sienna Drake, Cheen Euong Ang, Brandon M Walker, Thomas Vierbuchen, Daniel R Fuentes, Philip Brennecke, Kazuhiro R Nitta, Arttu Jolma, Lars M Steinmetz, Jussi Taipale, Thomas C Südhof, Marius Wernig
Normal differentiation and induced reprogramming require the activation of target cell programs and silencing of donor cell programs. In reprogramming, the same factors are often used to reprogram many different donor cell types. As most developmental repressors, such as RE1-silencing transcription factor (REST) and Groucho (also known as TLE), are considered lineage-specific repressors, it remains unclear how identical combinations of transcription factors can silence so many different donor programs. Distinct lineage repressors would have to be induced in different donor cell types...
April 13, 2017: Nature
https://www.readbyqxmd.com/read/28344001/inducible-and-deterministic-forward-programming-of-human-pluripotent-stem-cells-into-neurons-skeletal-myocytes-and-oligodendrocytes
#5
Matthias Pawlowski, Daniel Ortmann, Alessandro Bertero, Joana M Tavares, Roger A Pedersen, Ludovic Vallier, Mark R N Kotter
The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs has compromised efficiencies of forward programming approaches. We have systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy. This approach provides a powerful platform for the generation of human cell types by forward programming...
April 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28327614/partial-reprogramming-of-pluripotent-stem-cell-derived-cardiomyocytes-into-neurons
#6
Wenpo Chuang, Arun Sharma, Praveen Shukla, Guang Li, Moritz Mall, Kuppusamy Rajarajan, Oscar J Abilez, Ryoko Hamaguchi, Joseph C Wu, Marius Wernig, Sean M Wu
Direct reprogramming of somatic cells has been demonstrated, however, it is unknown whether electrophysiologically-active somatic cells derived from separate germ layers can be interconverted. We demonstrate that partial direct reprogramming of mesoderm-derived cardiomyocytes into neurons is feasible, generating cells exhibiting structural and electrophysiological properties of both cardiomyocytes and neurons. Human and mouse pluripotent stem cell-derived CMs (PSC-CMs) were transduced with the neurogenic transcription factors Brn2, Ascl1, Myt1l and NeuroD...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321434/transient-creb-mediated-transcription-is-key-in-direct-neuronal-reprogramming
#7
Sergio Gascón, Felipe Ortega, Magdalena Götz
Combinations of neuronal determinants and/or small-molecules such as Forskolin (Fk) can be used to convert different cell types into neurons. As Fk is known to activate cAMP-dependent pathways including CREB-activity, we aimed here to determine the role of CREB in reprogramming - including its temporal profile. We show that transient expression of the dominant-positive CREB-VP16 followed by its inactivation mediated by the dominant-negative ICER improves neuronal conversion of astrocytes mediated by the neurogenic determinant Ascl1...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28262173/cellular-models-to-study-schizophrenia-a-systematic-review
#8
REVIEW
Manasa Seshadri, Debanjan Banerjee, Biju Viswanath, K Ramakrishnan, Meera Purushottam, Ganesan Venkatasubramanian, Sanjeev Jain
BACKGROUND: Advancements in cellular reprogramming techniques have made it possible to directly study brain cells from patients with neuropsychiatric disorders. We have systematically reviewed the applications of induced pluripotent stem cells (IPSCs) and their neural derivatives in understanding the biological basis of schizophrenia. METHOD: We searched the scientific literature published in MEDLINE with the following search strategy: (Pluripotent) AND (Schizophrenia OR Antipsychotic OR Psychosis)...
February 2017: Asian Journal of Psychiatry
https://www.readbyqxmd.com/read/28230276/dissection-of-regulatory-elements-during-direct-conversion-of-somatic-cells-into-neurons
#9
Tahereh Soleimani, Nafiseh Falsafi, Hossein Fallahi
A revolutionary approach that involves direct conversion of somatic cells into almost any other types of cells showed promising results for regenerative medicine. Currently, producing valuable cell types including neurons, cardiomyocytes and hepatocytes through direct conversion of somatic cells appear to be a feasible option for regenerative medicine. The process involves inducing the cells by chemical cocktails or by expression of different types of transcription factors. In this concept, in vitro neurogenesis considered to be able to produce neuron cells to replace damaged neurons especially in Alzheimer and Parkinson disease...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28216149/direct-generation-of-human-neuronal-cells-from-adult-astrocytes-by-small-molecules
#10
Longfei Gao, Wuqiang Guan, Min Wang, Huihan Wang, Jiali Yu, Qing Liu, Binlong Qiu, Yongchun Yu, Yifang Ping, Xiuwu Bian, Li Shen, Gang Pei
Astrocytes, due to the proximity to neuronal lineage and capability to proliferate, are ideal starting cells to regenerate neurons. Human fetal astrocytes have been successfully converted into neuronal cells by small molecules, which offered a broader range of further applications than transcription factor-mediated neuronal reprogramming. Here we report that human adult astrocytes could also be converted into neuronal cells by a different set of small molecules. These induced cells exhibited typical neuronal morphologies, expressed neuronal markers, and displayed neuronal electrophysiological properties...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28191764/neural-progenitor-like-cells-induced-from-human-gingiva-derived-mesenchymal-stem-cells-regulate-myelination-of-schwann-cells-in-rat-sciatic-nerve-regeneration
#11
Qunzhou Zhang, Phuong Nguyen, Qilin Xu, Wonse Park, Sumin Lee, Akihiro Furuhashi, Anh D Le
Regeneration of peripheral nerve injury remains a major clinical challenge. Recently, mesenchymal stem cells (MSCs) have been considered as potential candidates for peripheral nerve regeneration; however, the underlying mechanisms remain elusive. Here, we show that human gingiva-derived MSCs (GMSCs) could be directly induced into multipotent NPCs (iNPCs) under minimally manipulated conditions without the introduction of exogenous genes. Using a crush-injury model of rat sciatic nerve, we demonstrate that GMSCs transplanted to the injury site could differentiate into neuronal cells, whereas iNPCs could differentiate into both neuronal and Schwann cells...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28186702/direct-conversion-of-human-fibroblasts-into-schwann-cells-that-facilitate-regeneration-of-injured-peripheral-nerve-in-vivo
#12
Yoshihiro Sowa, Tsunao Kishida, Koichi Tomita, Kenta Yamamoto, Toshiaki Numajiri, Osam Mazda
Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs)...
April 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28145631/generation-of-integration-free-induced-neurons-using-graphene-oxide-polyethylenimine
#13
Soonbong Baek, Jaesur Oh, Juhyun Song, Hwan Choi, Junsang Yoo, Gui-Yeon Park, Jin Han, Yujung Chang, Hanseul Park, Hongwon Kim, Ssang-Goo Cho, Byung-Soo Kim, Jongpil Kim
Direct conversion of somatic cells into induced neurons (iNs) without inducing pluripotency has great therapeutic potential for treating central nervous system diseases. Reprogramming of somatic cells to iNs requires the introduction of several factors that drive cell-fate conversion, and viruses are commonly used to deliver these factors into somatic cells. However, novel gene-delivery systems that do not integrate transgenes into the genome are required to generate iNs for safe human clinical applications...
February 2017: Small
https://www.readbyqxmd.com/read/28099929/modeling-the-phenotype-of-spinal-muscular-atrophy-by-the-direct-conversion-of-human-fibroblasts-to-motor-neurons
#14
Qi-Jie Zhang, Jin-Jing Li, Xiang Lin, Ying-Qian Lu, Xin-Xin Guo, En-Lin Dong, Miao Zhao, Jin He, Ning Wang, Wan-Jin Chen
Spinal muscular atrophy (SMA) is a lethal autosomal recessive neurological disease characterized by selective degeneration of motor neurons in the spinal cord. In recent years, the development of cellular reprogramming technology has provided an alternative and effective method for obtaining patient-specific neurons in vitro. In the present study, we applied this technology to the field of SMA to acquire patient-specific induced motor neurons that were directly converted from fibroblasts via the forced expression of 8 defined transcription factors...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/27981499/direct-conversion-of-somatic-cells-into-induced-neurons
#15
REVIEW
Na An, Huiming Xu, Wei-Qiang Gao, Hao Yang
The progressive loss and degeneration of neurons in the central nervous system (CNS), as a result of traumas or diseases including Alzheimer's, Parkinson's, Huntington's disease, stroke, and traumatic injury to the brain and spinal cord, can usually have devastating effects on quality of life. The current strategies available for treatments are described including drug delivery, surgery, electrical stimulation, and cell-based tissue engineering approaches. However, apart from cell-based therapy, other attempts are limited in improving clinical outcomes...
December 16, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27979736/the-expanding-horizon-of-micrornas-in-cellular-reprogramming
#16
REVIEW
Yogita K Adlakha, Pankaj Seth
Research over the last few years in cellular reprogramming has enlightened the magical potential of microRNAs (miRNAs) in changing the cell fate from somatic to pluripotent. Recent investigations on exploring the role(s) of miRNAs in somatic cell reprogramming revealed that they target a wide range of molecules and refine their protein output. This leads to fine tuning of distinct cellular processes including cell cycle, signalling pathways, transcriptional activation/silencing and epigenetic modelling. The concerted actions of miRNA on different pathways simultaneously strengthen the transition from a differentiated to de-differentiated state...
December 12, 2016: Progress in Neurobiology
https://www.readbyqxmd.com/read/27943183/generation-of-spinal-motor-neurons-from-human-pluripotent-stem-cells
#17
David P Santos, Evangelos Kiskinis
Human embryonic stem cells (ESCs) are characterized by their unique ability to self-renew indefinitely, as well as to differentiate into any cell type of the human body. Induced pluripotent stem cells (iPSCs) share these salient characteristics with ESCs and can easily be generated from any given individual by reprogramming somatic cell types such as fibroblasts or blood cells. The spinal motor neuron (MN) is a specialized neuronal subtype that synapses with muscle to control movement. Here, we present a method to generate functional, postmitotic, spinal motor neurons through the directed differentiation of ESCs and iPSCs by the use of small molecules...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27917895/small-molecules-increase-direct-neural-conversion-of-human-fibroblasts
#18
Ulrich Pfisterer, Fredrik Ek, Stefan Lang, Shamit Soneji, Roger Olsson, Malin Parmar
The generation of human induced neurons (hiNs) via exogenous delivery of neural transcription factors represents a novel technique to obtain disease and patient specific neurons. These cells have the potential to be used for disease modeling, diagnostics and drug screening, and also to be further developed for brain repair. In the present study, we utilized hiNs to develop an unbiased screening assay for small molecules that increase the conversion efficiency. Using this assay, we screened 307 compounds from five annotated libraries and identified six compounds that were very potent in potentiating the reprogramming process...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27857203/rapid-and-efficient-crispr-cas9-gene-inactivation-in-human-neurons-during-human-pluripotent-stem-cell-differentiation-and-direct-reprogramming
#19
Alicia Rubio, Mirko Luoni, Serena G Giannelli, Isabella Radice, Angelo Iannielli, Cinzia Cancellieri, Claudia Di Berardino, Giulia Regalia, Giovanna Lazzari, Andrea Menegon, Stefano Taverna, Vania Broccoli
The CRISPR/Cas9 system is a rapid and customizable tool for gene editing in mammalian cells. In particular, this approach has widely opened new opportunities for genetic studies in neurological disease. Human neurons can be differentiated in vitro from hPSC (human Pluripotent Stem Cells), hNPCs (human Neural Precursor Cells) or even directly reprogrammed from fibroblasts. Here, we described a new platform which enables, rapid and efficient CRISPR/Cas9-mediated genome targeting simultaneously with three different paradigms for in vitro generation of neurons...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27822179/plasmid-based-generation-of-induced-neural-stem-cells-from-adult-human-fibroblasts
#20
Philipp Capetian, Luis Azmitia, Martje G Pauly, Victor Krajka, Felix Stengel, Eva-Maria Bernhardi, Mariana Klett, Britta Meier, Philip Seibler, Nancy Stanslowsky, Andreas Moser, Andreas Knopp, Gabriele Gillessen-Kaesbach, Guido Nikkhah, Florian Wegner, Máté Döbrössy, Christine Klein
Direct reprogramming from somatic to neural cell types has become an alternative to induced pluripotent stem cells. Most protocols employ viral expression systems, posing the risk of random genomic integration. Recent developments led to plasmid-based protocols, lowering this risk. However, these protocols either relied on continuous presence of a variety of small molecules or were only able to reprogram murine cells. We therefore established a reprogramming protocol based on vectors containing the Epstein-Barr virus (EBV)-derived oriP/EBNA1 as well as the defined expression factors Oct3/4, Sox2, Klf4, L-myc, Lin28, and a small hairpin directed against p53...
2016: Frontiers in Cellular Neuroscience
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