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https://www.readbyqxmd.com/read/28697461/direct-induction-of-functional-neuronal-cells-from-fibroblast-like-cells-derived-from-adult-human-retina
#1
Lili Hao, Zhen Xu, Hui Sun, Wu Luo, Youchen Yan, Jing Wang, Jingyi Guo, Yizhi Liu, Shuyi Chen
Obtaining and manipulating neuronal cells are critical for neural biology basic mechanism studies and translational applications. Recent advances in protocol development and mechanism dissections have made direct induction of neuronal cells from other somatic cells (iN) a promising strategy for such purposes. In this study, we established a protocol to expand a population of fibroblast-like cells from adult human retinal tissues, which can be reprogrammed into iNs by forced expression of neurogenic transcription factors...
June 29, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28690140/new-neurons-in-adult-brain-distribution-molecular-mechanisms-and-therapies
#2
REVIEW
Annachiara Pino, Guido Fumagalli, Francesco Bifari, Ilaria Decimo
"Are new neurons added in the adult mammalian brain?" "Do neural stem cells activate following CNS diseases?" "How can we modulate their activation to promote recovery?" Recent findings in the field provide novel insights for addressing these questions from a new perspective. In this review, we will summarize the current knowledge about adult neurogenesis and neural stem cell niches in healthy and pathological conditions. We will first overview the milestones that have led to the discovery of the classical ventricular and hippocampal neural stem cell niches...
July 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28686866/direct-neuronal-reprogramming-achievements-hurdles-and-new-roads-to-success
#3
REVIEW
Sergio Gascón, Giacomo Masserdotti, Gianluca Luigi Russo, Magdalena Götz
The ability to directly reprogram mature cells to alternative fates challenges concepts of how cell identities are maintained, erased, and acquired. Recent advances in understanding and overcoming hurdles to direct neuronal conversion have provided new insights into mechanisms that maintain cell identity programs and have enabled high efficiency reprogramming in vivo. We discuss key cell-intrinsic molecular and metabolic constraints that influence the establishment of a new identity as well as environmental inputs from injured brains that favor or harm the conversion process...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28664454/microrna-directed-neuronal-reprogramming-as-a-therapeutic-strategy-for-neurological-diseases
#4
REVIEW
Irene Faravelli, Stefania Corti
The loss of neurons due to injury and disease results in a wide spectrum of highly disabling neurological and neurodegenerative conditions, given the apparent limited capacity of endogenous repair of the adult central nervous system (CNS). Therefore, it is important to develop technologies that can promote de novo neural stem cell and neuron generation. Current insights in CNS development and cellular reprogramming have provided the knowledge to finely modulate lineage-restricted transcription factors and microRNAs (miRNA) to elicit correct neurogenesis...
June 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28648365/direct-reprogramming-of-fibroblasts-via-a-chemically-induced-xen-like-state
#5
Xiang Li, Defang Liu, Yantao Ma, Xiaomin Du, Junzhan Jing, Lipeng Wang, Bingqing Xie, Da Sun, Shaoqiang Sun, Xueqin Jin, Xu Zhang, Ting Zhao, Jingyang Guan, Zexuan Yi, Weifeng Lai, Ping Zheng, Zhuo Huang, Yanzhong Chang, Zhen Chai, Jun Xu, Hongkui Deng
Direct lineage reprogramming, including with small molecules, has emerged as a promising approach for generating desired cell types. We recently found that during chemical induction of induced pluripotent stem cells (iPSCs) from mouse fibroblasts, cells pass through an extra-embryonic endoderm (XEN)-like state. Here, we show that these chemically induced XEN-like cells can also be induced to directly reprogram into functional neurons, bypassing the pluripotent state. The induced neurons possess neuron-specific expression profiles, form functional synapses in culture, and further mature after transplantation into the adult mouse brain...
June 20, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28646119/rest-suppression-mediates-neural-conversion-of-adult-human-fibroblasts-via-microrna-dependent-and-independent-pathways
#6
Janelle Drouin-Ouellet, Shong Lau, Per Ludvik Brattås, Daniella Rylander Ottosson, Karolina Pircs, Daniela A Grassi, Lucy M Collins, Romina Vuono, Annika Andersson Sjöland, Gunilla Westergren-Thorsson, Caroline Graff, Lennart Minthon, Håkan Toresson, Roger A Barker, Johan Jakobsson, Malin Parmar
Direct conversion of human fibroblasts into mature and functional neurons, termed induced neurons (iNs), was achieved for the first time 6 years ago. This technology offers a promising shortcut for obtaining patient- and disease-specific neurons for disease modeling, drug screening, and other biomedical applications. However, fibroblasts from adult donors do not reprogram as easily as fetal donors, and no current reprogramming approach is sufficiently efficient to allow the use of this technology using patient-derived material for large-scale applications...
June 23, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28597071/the-novel-tool-of-cell-reprogramming-for-applications-in-molecular-medicine
#7
REVIEW
Moritz Mall, Marius Wernig
Recent discoveries in the field of stem cell biology have enabled scientists to "reprogram" cells from one type to another. For example, it is now possible to place adult skin or blood cells in a dish and convert them into neurons, liver, or heart cells. It is also possible to literally "rejuvenate" adult cells by reprogramming them into embryonic-like stem cells, which in turn can be differentiated into every tissue and cell type of the human body. Our ability to reprogram cell types has four main implications for medicine: (1) scientists can now take skin or blood cells from patients and convert them to other cells to study disease processes...
July 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28580167/sequential-emt-met-induces-neuronal-conversion-through-sox2
#8
Songwei He, Jinlong Chen, Yixin Zhang, Mengdan Zhang, Xiao Yang, Yuan Li, Hao Sun, Lilong Lin, Ke Fan, Lining Liang, Chengqian Feng, Fuhui Wang, Xiao Zhang, Yiping Guo, Duanqing Pei, Hui Zheng
Direct neuronal conversion can be achieved with combinations of small-molecule compounds and growth factors. Here, by studying the first or induction phase of the neuronal conversion induced by defined 5C medium, we show that the Sox2-mediated switch from early epithelial-mesenchymal transition (EMT) to late mesenchymal-epithelial transition (MET) within a high proliferation context is essential and sufficient for the conversion from mouse embryonic fibroblasts (MEFs) to TuJ(+) cells. At the early stage, insulin and basic fibroblast growth factor (bFGF)-induced cell proliferation, early EMT, the up-regulation of Stat3 and Sox2, and the subsequent activation of neuron projection...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28552236/brain-repair-from-intrinsic-cell-sources-turning-reactive-glia-into-neurons
#9
Olof Torper, Magdalena Götz
The replacement of lost neurons in the brain due to injury or disease holds great promise for the treatment of neurological disorders. However, logistical and ethical hurdles in obtaining and maintaining viable cells for transplantation have proven difficult to overcome. In vivo reprogramming offers an alternative, to bypass many of the restrictions associated with an exogenous cell source as it relies on a source of cells already present in the brain. Recent studies have demonstrated the possibility to target and reprogram glial cells into functional neurons with high efficiency in the murine brain, using virally delivered transcription factors...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552235/reprogramming-of-somatic-cells-ips-and-in-cells
#10
Vania Broccoli
Limited access to human neurons has posed a significant barrier to progress in biological and preclinical studies of the human nervous system. The advent of cell reprogramming technologies has widely disclosed unprecedented opportunities to generate renewable sources of human neural cells for disease modeling, drug discovery, and cell therapeutics. Both somatic reprogramming into induced pluripotent stem cells (iPSCs) and directly induced Neurons (iNeurons) rely on transcription factor-based cellular conversion processes...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28536395/cellular-and-molecular-preconditions-for-retinal-pigment-epithelium-rpe-natural-reprogramming-during-retinal-regeneration-in-urodela
#11
REVIEW
Eleonora N Grigoryan, Yuliya V Markitantova
Many regeneration processes in animals are based on the phenomenon of cell reprogramming followed by proliferation and differentiation in a different specialization direction. An insight into what makes natural (in vivo) cell reprogramming possible can help to solve a number of biomedical problems. In particular, the first problem is to reveal the intrinsic properties of the cells that are necessary and sufficient for reprogramming; the second, to evaluate these properties and, on this basis, to reveal potential endogenous sources for cell substitution in damaged tissues; and the third, to use the acquired data for developing approaches to in vitro cell reprogramming in order to obtain a cell reserve for damaged tissue repair...
December 1, 2016: Biomedicines
https://www.readbyqxmd.com/read/28480968/the-influence-of-raav2-mediated-sox2-delivery-into-neonatal-and-adult-human-rpe-cells-a-comparative-study
#12
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 toward 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 reprogramming 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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