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neuron reprogramming

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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/28685029/does-gastric-bypass-surgery-change-body-weight-set-point
#4
REVIEW
Z Hao, M B Mumphrey, C D Morrison, H Münzberg, J Ye, H R Berthoud
The relatively stable body weight during adulthood is attributed to a homeostatic regulatory mechanism residing in the brain which uses feedback from the body to control energy intake and expenditure. This mechanism guarantees that if perturbed up or down by design, body weight will return to pre-perturbation levels, defined as the defended level or set point. The fact that weight re-gain is common after dieting suggests that obese subjects defend a higher level of body weight. Thus, the set point for body weight is flexible and likely determined by the complex interaction of genetic, epigenetic and environmental factors...
December 2016: International Journal of Obesity Supplements
https://www.readbyqxmd.com/read/28664454/microrna-directed-neuronal-reprogramming-as-a-therapeutic-strategy-for-neurological-diseases
#5
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/28654077/protocol-for-the-differentiation-of-human-induced-pluripotent-stem-cells-into-mixed-cultures-of-neurons-and-glia-for-neurotoxicity-testing
#6
Francesca Pistollato, David Canovas-Jorda, Dimitra Zagoura, Anna Price
Human pluripotent stem cells can differentiate into various cell types that can be applied to human-based in vitro toxicity assays. One major advantage is that the reprogramming of somatic cells to produce human induced pluripotent stem cells (hiPSCs) avoids the ethical and legislative issues related to the use of human embryonic stem cells (hESCs). HiPSCs can be expanded and efficiently differentiated into different types of neuronal and glial cells, serving as test systems for toxicity testing and, in particular, for the assessment of different pathways involved in neurotoxicity...
June 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28648365/direct-reprogramming-of-fibroblasts-via-a-chemically-induced-xen-like-state
#7
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
#8
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/28641110/sox11-expression-promotes-regeneration-of-some-retinal-ganglion-cell-types-but-kills-others
#9
Michael W Norsworthy, Fengfeng Bei, Riki Kawaguchi, Qing Wang, Nicholas M Tran, Yi Li, Benedikt Brommer, Yiming Zhang, Chen Wang, Joshua R Sanes, Giovanni Coppola, Zhigang He
At least 30 types of retinal ganglion cells (RGCs) send distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration of other types. From a screen of transcription factors, we identified Sox11 as one that could induce substantial axon regeneration...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28637872/hydrogen-sulfide-modulates-eukaryotic-translation-initiation-factor-2%C3%AE-eif2%C3%AE-phosphorylation-status-in-the-integrated-stress-response-pathway
#10
Vinita Yadav, Xing-Huang Gao, Belinda Willard, Maria Hatzoglou, Ruma Banerjee, Omer Kabil
Hydrogen sulfide (H2S) regulates various physiological processes including neuronal activity, vascular tone, inflammation, and energy metabolism. Moreover, H2S elicits cytoprotective effects against stressors in various cellular models of injury. However, the mechanism of the signaling pathways mediating the cytoprotective functions of H2S is not well understood. We previously uncovered a heme-dependent metabolic switch for transient induction of H2S production in the transsulfuration pathway. Here, we demonstrate that increased endogenous H2S production or its exogenous administration modulates major components of the integrated stress response (ISR) promoting a metabolic state primed for stress response...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28634230/similarity-in-gene-regulatory-networks-suggests-that-cancer-cells-share-characteristics-of-embryonic-neural-cells
#11
Zan Zhang, Anhua Lei, Liyang Xu, Lu Chen, Yonglong Chen, Xuena Zhang, Yan Gao, Xiaoli Yang, Min Zhang, Ying Cao
Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and re-differentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that, inhibition of the epigenetic modification enzymes enhancer of zeste homolog 2 (EZH2), histone deacetylases (HDACs) 1 and 3, lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28627365/mitochondria-metabolic-reprogramming-in-the-formation-of-neurons-from-peripheral-cells-cause-or-consequence-and-the-implications-to-their-utility
#12
REVIEW
Gary E Gibson, Ankita Thakkar
The induction of pluripotent stem cells (iPSC) from differentiated cells such as fibroblasts and their subsequent conversion to neural progenitor cells (NPC) and finally to neurons is intriguing scientifically, and its potential to medicine nearly infinite, but unrealized. A better understanding of the changes at each step of the transformation will enable investigators to use them better to model neurological disease. Each step of conversion from a differentiated cell to an iPSC to a NPC to neurons requires large changes in glycolysis including aerobic glycolysis, the pentose shunt, the tricarboxylic acid cycle, the electron transport chain and in the production of reactive oxygen species (ROS)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28614042/bnip3l-nix-dependent-mitophagy-regulates-cell-differentiation-via-metabolic-reprogramming
#13
Lorena Esteban-Martínez, Patricia Boya
Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiological retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming towards glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28602612/lineage-reprogramming-of-astroglial-cells-from-different-origins-into-distinct-neuronal-subtypes
#14
Malek Chouchane, Ana Raquel Melo de Farias, Daniela Maria de Sousa Moura, Markus Michael Hilscher, Timm Schroeder, Richardson Naves Leão, Marcos Romualdo Costa
Astroglial cells isolated from the rodent postnatal cerebral cortex are particularly susceptible to lineage reprogramming into neurons. However, it remains unknown whether other astroglial populations retain the same potential. Likewise, little is known about the fate of induced neurons (iNs) in vivo. In this study we addressed these questions using two different astroglial populations isolated from the postnatal brain reprogrammed either with Neurogenin-2 (Neurog2) or Achaete scute homolog-1 (Ascl1). We show that cerebellum (CerebAstro) and cerebral cortex astroglia (CtxAstro) generates iNs with distinctive neurochemical and morphological properties...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28597071/the-novel-tool-of-cell-reprogramming-for-applications-in-molecular-medicine
#15
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/28593578/induced-pluripotent-stem-cell-based-modeling-of-neurodegenerative-diseases-a-focus-on-autophagy
#16
REVIEW
Johannes Jungverdorben, Andreas Till, Oliver Brüstle
The advent of cell reprogramming has enabled the generation of induced pluripotent stem cells (iPSCs) from patient skin fibroblasts or blood cells and their subsequent differentiation into tissue-specific cells, including neurons and glia. This approach can be used to recapitulate disease-specific phenotypes in classical cell culture paradigms and thus represents an invaluable asset for disease modeling and drug validation in the framework of personalized medicine. The autophagy pathway is a ubiquitous eukaryotic degradation and recycling system, which relies on lysosomal degradation of unwanted and potentially cytotoxic components...
July 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28592657/induced-pluripotent-stem-cell-models-of-lysosomal-storage-disorders
#17
REVIEW
Daniel K Borger, Benjamin McMahon, Tamanna Roshan Lal, Jenny Serra-Vinardell, Elma Aflaki, Ellen Sidransky
Induced pluripotent stem cells (iPSCs) have provided new opportunities to explore the cell biology and pathophysiology of human diseases, and the lysosomal storage disorder research community has been quick to adopt this technology. Patient-derived iPSC models have been generated for a number of lysosomal storage disorders, including Gaucher disease, Pompe disease, Fabry disease, metachromatic leukodystrophy, the neuronal ceroid lipofuscinoses, Niemann-Pick types A and C1, and several of the mucopolysaccharidoses...
June 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28585386/understanding-neurodevelopmental-disorders-using-human-pluripotent-stem-cell-derived-neurons
#18
Claudia Tamburini, Meng Li
Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of patient-specific cells, which in principle can be differentiated into all disease-relevant somatic cell types to create in vitro models of the disorder of interest. Here, neuronal differentiation protocols available for this purpose and the current progress on iPSCs-based models of schizophrenia, autism spectrum disorders and bipolar disorder were reviewed...
July 2017: Brain Pathology
https://www.readbyqxmd.com/read/28585381/modeling-parkinson-s-disease-with-induced-pluripotent-stem-cells-harboring-%C3%AE-synuclein-mutations
#19
Karamjit Singh Dolt, Fella Hammachi, Tilo Kunath
Parkinson's disease (PD) is a common neurodegenerative condition affecting more than 8 million people worldwide. Although, the majority of PD cases are sporadic in nature, there are a growing number of monogenic mutations identified to cause PD in a highly penetrant manner. Many of these familial mutations give rise to a condition that is clinically and neuropathologically similar, if not identical, to sporadic PD. Mutations in genes such as SNCA cause PD in an autosomal dominant manner and patients have motor and non-motor symptoms that are typical for sporadic PD...
July 2017: Brain Pathology
https://www.readbyqxmd.com/read/28580186/mash1-dependent-notch-signaling-pathway-regulates-gabaergic-neuron-like-differentiation-from-bone-marrow-derived-mesenchymal-stem-cells
#20
Qianfa Long, Qiang Luo, Kai Wang, Adrian Bates, Ashok K Shetty
GABAergic neuronal cell grafting has promise for treating a multitude of neurological disorders including epilepsy, age-related memory dysfunction, Alzheimer's disease and schizophrenia. However, identification of an unlimited source of GABAergic cells is critical for advancing such therapies. Our previous study implied that reprogramming of bone marrow-derived mesenchymal stem cells (BMSCs) through overexpression of the Achaete-scute homolog 1 (Ascl1, also called Mash1) could generate GABAergic neuron-like cells...
May 2017: Aging and Disease
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