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https://www.readbyqxmd.com/read/29331684/reprogramming-neurodegeneration-in-the-big-data-era
#1
REVIEW
Lujia Zhou, Patrik Verstreken
Recent genome-wide association studies (GWAS) have identified numerous genetic risk variants for late-onset Alzheimer's disease (AD) and Parkinson's disease (PD). However, deciphering the functional consequences of GWAS data is challenging due to a lack of reliable model systems to study the genetic variants that are often of low penetrance and non-coding identities. Pluripotent stem cell (PSC) technologies offer unprecedented opportunities for molecular phenotyping of GWAS variants in human neurons and microglia...
January 10, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29328434/chemical-conversion-of-human-lung-fibroblasts-into-neuronal-cells
#2
Xiao-Yu Wan, Li-Yun Xu, Bing Li, Qiu-Hong Sun, Qiu-Liang Ji, Dong-Dong Huang, Lan Zhao, Yong-Tao Xiao
It has been previously reported that human embryonic fibroblasts and mouse embryonic fibroblasts can be converted into neuronal cells using chemical agents, along with forced expression specific transcriptional factors. However, the materials required for reprogramming in these approaches presents major technical difficulties and safety concerns. The current study investigated whether a cocktail of small molecules can convert human lung fibroblast cells into neurons. The small molecules valproic acid, CHIR99021, DMH1, Repsox, forskolin, Y‑27632 and SP600125 (VCHRFYS) were used to induce MRC‑5 cells into neuronal cells in vitro...
January 10, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29327201/allele-specific-biased-expression-of-the-cntn6-gene-in-ips-cell-derived-neurons-from-a-patient-with-intellectual-disability-and-3p26-3-microduplication-involving-the-cntn6-gene
#3
Maria M Gridina, Natalia M Matveeva, Veniamin S Fishman, Aleksei G Menzorov, Helen A Kizilova, Nikolay A Beregovoy, Igor I Kovrigin, Inna E Pristyazhnyuk, Igor P Oscorbin, Maxim L Filipenko, Anna A Kashevarova, Nikolay A Skryabin, Tatyana V Nikitina, Elena A Sazhenova, Ludmila P Nazarenko, Igor N Lebedev, Oleg L Serov
Copy number variations (CNVs) of the human CNTN6 gene caused by megabase-scale microdeletions or microduplications in the 3p26.3 region are often the cause of neurodevelopmental disorders, including intellectual disability and developmental delay. Surprisingly, patients with different copy numbers of this gene display notable overlapping of neuropsychiatric symptoms. The complexity of the study of human neuropathologies is associated with the inaccessibility of brain material. This problem can be overcome through the use of reprogramming technologies that permit the generation of induced pluripotent stem (iPS) cells from fibroblasts and their subsequent in vitro differentiation into neurons...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29311646/generation-of-functional-dopaminergic-neurons-from-reprogramming-fibroblasts-by-nonviral-based-mesoporous-silica-nanoparticles
#4
Jen-Hsuan Chang, Ping-Hsing Tsai, Kai-Yi Wang, Yu-Ting Wei, Shih-Hwa Chiou, Chung-Yuan Mou
Direct-lineage conversion of the somatic cell by reprogramming, in which mature cells were fully converted into a variety of other cell types bypassing an intermediate pluripotent state, is a promising regenerative medicine approach. Due to the risk of tumorigenesis by viral methods, a non-viral carrier for the delivery of reprogramming factors is very desirable. This study utilized the mesoporous silica nanoparticles (MSNs) as a non-viral delivery system for transduction of the three key factors to achieve conversion of mouse fibroblasts (MFs) into functional dopaminergic neuron-like cells (denoted as fDA-neurons)...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311261/towards-stem-cell-based-therapies-for-parkinson-s-disease
#5
Malin Parmar
Treating neurodegenerative diseases with cell transplantation has been within reach since the first pioneering clinical trials in which dopamine neuron progenitors from the fetal brain were transplanted to individuals with Parkinson's disease. However, the use of fetal tissue is problematic in terms of low availability and high variability, and it is also associated with ethical concerns that vary between countries. For decades, the field has therefore investigated new scalable source of therapeutic cells from stem cells or via reprogramming...
January 8, 2018: Development
https://www.readbyqxmd.com/read/29291346/analysis-of-transcriptional-activity-by-the-myt1-and-myt1l-transcription-factors
#6
Arkadi Manukyan, Izabela Kowalczyk, Tiffany A Melhuish, Agata Lemiesz, David Wotton
Myt1 and Myt1l (Myelin transcription factor 1, and Myt1-like) are members of a small family of closely related zinc finger transcription factors, characterized by two clusters of C2HC zinc fingers. Both are widely expressed during early embryogenesis, but are largely restricted to expression within the brain in the adult. Myt1l, as part of a three transcription factor mix, can reprogram fibroblasts to neurons and plays a role in maintaining neuronal identity. Previous analyses have indicated roles in both transcriptional activation and repression and suggested that Myt1 and Myt1l may have opposing functions in gene expression...
January 1, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29287743/a-novel-ex-vivo-method-for-measuring-whole-brain-metabolism-in-model-systems
#7
Kathryn E Neville, Timothy L Bosse, Mia Klekos, John F Mills, Steven E Weicksel, James S Waters, Marla Tipping
BACKGROUND: Many neuronal and glial diseases have been associated with changes in metabolism. Therefore, metabolic reprogramming has become an important area of research to better understand disease at the cellular level, as well as to identify targets for treatment. Model systems are ideal for interrogating metabolic questions in a tissue dependent context. However, while new tools have been developed to study metabolism in cultured cells there has been less progress towards studies in vivo and ex vivo...
December 26, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29287724/paris-reprograms-glucose-metabolism-by-hif-1%C3%AE-induction-in-dopaminergic-neurodegeneration
#8
Hojin Kang, Areum Jo, Hyein Kim, Rin Khang, Ji-Yeong Lee, Hanna Kim, Chi-Hu Park, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Our previous study found that PARIS (ZNF746) transcriptionally suppressed transketolase (TKT), a key enzyme in pentose phosphate pathway (PPP) in the substantia nigra (SN) of AAV-PARIS injected mice. In this study, we revealed that PARIS overexpression reprogrammed glucose metabolic pathway, leading to the increment of glycolytic proteins along with TKT reduction in the SN of AAV-PARIS injected mice. Knock-down of TKT in differentiated SH-SY5Y cells led to an increase of glycolytic enzymes and decrease of PPP-related enzymes whereas overexpression of TKT restored PARIS-mediated glucose metabolic shift, suggesting that glucose metabolic alteration by PARIS is TKT-dependent...
December 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29282205/glycosphingolipid-metabolic-reprogramming-drives-neural-differentiation
#9
Domenico Russo, Floriana Della Ragione, Riccardo Rizzo, Eiji Sugiyama, Francesco Scalabrì, Kei Hori, Serena Capasso, Lucia Sticco, Salvatore Fioriniello, Roberto De Gregorio, Ilaria Granata, Mario R Guarracino, Vittorio Maglione, Ludger Johannes, Gian Carlo Bellenchi, Mikio Hoshino, Mitsutoshi Setou, Maurizio D'Esposito, Alberto Luini, Giovanni D'Angelo
Neural development is accomplished by differentiation events leading to metabolic reprogramming. Glycosphingolipid metabolism is reprogrammed during neural development with a switch from globo- to ganglio-series glycosphingolipid production. Failure to execute this glycosphingolipid switch leads to neurodevelopmental disorders in humans, indicating that glycosphingolipids are key players in this process. Nevertheless, both the molecular mechanisms that control the glycosphingolipid switch and its function in neurodevelopment are poorly understood...
December 27, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29239312/endogenous-retinal-neural-stem-cell-reprogramming-for-neuronal-regeneration
#10
REVIEW
Romain Madelaine, Philippe Mourrain
In humans, optic nerve injuries and associated neurodegenerative diseases are often followed by permanent vision loss. Consequently, an important challenge is to develop safe and effective methods to replace retinal neurons and thereby restore neuronal functions and vision. Identifying cellular and molecular mechanisms allowing to replace damaged neurons is a major goal for basic and translational research in regenerative medicine. Contrary to mammals, the zebrafish has the capacity to fully regenerate entire parts of the nervous system, including retina...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29236331/reduction-of-two-histone-marks-h3k9me3-and-h3k27me3-by-epidrug-induces-neuroendocrine-differentiation-in-prostate-cancer
#11
Eunsohl Lee, Jingcheng Wang, Younghun Jung, Frank C Cackowski, Russell S Taichman
Neuroendocrine prostate cancer (NE PCa) is an aggressive malignancy, often presenting with advanced metastasis. We previously reported that reduction of histone marks regulated by DNMT1 following epidrug (5-Azacitidine, 5-Aza) treatment controls induction of epithelial to mesenchymal (EMT) and a cancer stem cell (CSC) phenotype, which facilitates tumorigenesis in PCa cells. Here, we use the epidrug 5-Aza as a model for how histone marks may regulate the reprogramming of prostate adenocarcinoma into NE phenotypic cells...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29228630/transplantation-of-ips-cell-derived-neural-progenitors-overexpressing-sdf-1%C3%AE-increases-regeneration-and-functional-recovery-after-ischemic-stroke
#12
Monica Chau, Todd C Deveau, Mingke Song, Zheng Z Wei, Xiaohuan Gu, Shan Ping Yu, Ling Wei
Ischemic stroke is a leading cause of human death and disability while clinical treatments are limited. The adult brain possesses endogenous regenerative activities that may benefit tissue repair after stroke. Trophic factors such as stromal cell-derived factor 1 alpha (SDF-1α) are upregulated in the ischemic brain, which promote endogenous regeneration. The regenerative response, however, is normally insufficient. Transplantation of exogenous cells has been explored as regenerative therapies. One promising cell type for transplantation is induced pluripotent stem (iPS) cells which are cells genetically reprogrammed from adult somatic cells...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29174617/mir-302-367-induced-neurons-reduce-behavioral-impairment-in-an-experimental-model-of-alzheimer-s-disease
#13
Maryam Ghasemi-Kasman, Amir Shojaei, Mohammad Gol, Ali Akbar Moghadamnia, Hossein Baharvand, Mohammad Javan
In vivo reprogramming of reactive glial cells to neurons has opened a new horizon in regenerative medicine. Our previous study showed that astrocytes could be converted to neurons by the microRNA-302/367 (miR-302/367) cluster in adult brains. In this study, we investigated the possible contribution of miR-302/367-induced neurons in behavioral improvement and neural repair in an Alzheimer's disease (AD) animal model. The AD model was induced by an intracerebroventricular (i.c.v) injection of streptozotocin (STZ)...
November 24, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29174574/enhanced-neurogenesis-in-degenerated-hippocampi-following-pretreatment-with-mir-302-367-expressing-lentiviral-vector-in-mice
#14
Maryam Ghasemi-Kasman, Hossein Baharvand, Mohammad Javan
Astrogliosis is the main landmark of neurodegenerative diseases. In vivo reprogramming of reactive astrocytes to functional neurons opened a new horizon in regenerative medicine. However there is little evidence that show possible application of in vivo reprogramming approaches for enhancement of neurogenesis. Cluster miR-302/367 showed high capability in cell reprogramming. Here we show that application of lentiviral particles expressing cluster miR-302/367 along with systemic valproate (VPA) enhanced the capability of mice brains for neurogenesis in CA3 area following kainic acid (KA) induced hippocampal neurodegeneration...
November 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29174332/injury-induces-endogenous-reprogramming-and-dedifferentiation-of-neuronal-progenitors-to-multipotency
#15
Brian Lin, Julie H Coleman, Jesse N Peterson, Matthew J Zunitch, Woochan Jang, Daniel B Herrick, James E Schwob
Adult neurogenesis in the olfactory epithelium is often depicted as a unidirectional pathway during homeostasis and repair. We challenge the unidirectionality of this model by showing that epithelial injury unlocks the potential for Ascl1+ progenitors and Neurog1+ specified neuronal precursors to dedifferentiate into multipotent stem/progenitor cells that contribute significantly to tissue regeneration in the murine olfactory epithelium (OE). We characterize these dedifferentiating cells using several lineage-tracing strains and single-cell mRNA-seq, and we show that Sox2 is required for initiating dedifferentiation and that inhibition of Ezh2 promotes multipotent progenitor expansion...
November 20, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29174331/constitutively-active-smad2-3-are-broad-scope-potentiators-of-transcription-factor-mediated-cellular-reprogramming
#16
Tyson Ruetz, Ulrich Pfisterer, Bruno Di Stefano, James Ashmore, Meryam Beniazza, Tian V Tian, Daniel F Kaemena, Luca Tosti, Wenfang Tan, Jonathan R Manning, Eleni Chantzoura, Daniella Rylander Ottosson, Samuel Collombet, Anna Johnsson, Erez Cohen, Kosuke Yusa, Sten Linnarsson, Thomas Graf, Malin Parmar, Keisuke Kaji
Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constitutively active SMAD2/3 significantly improves the efficiency of induced pluripotent stem cell (iPSC) generation by the Yamanaka factors...
November 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29170823/engineering-new-neurons-in-vivo-reprogramming-in-mammalian-brain-and-spinal-cord
#17
REVIEW
Lei-Lei Wang, Chun-Li Zhang
Neurons are postmitotic. Once lost because of injury or degeneration, they do not regenerate in most regions of the mammalian central nervous system. Recent advancements nevertheless clearly reveal that new neurons can be reprogrammed from non-neuronal cells, especially glial cells, in the adult mammalian brain and spinal cord. Here, we give a brief overview concerning cell fate reprogramming in vivo and then focus on the underlying molecular and cellular mechanisms. Specifically, we critically review the cellular sources and the reprogramming factors for in vivo neuronal conversion...
November 23, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29168031/neural-cells-generated-from-human-induced-pluripotent-stem-cells-as-a-model-of-cns-involvement-in-mucopolysaccharidosis-type-ii
#18
Jitka Rybová, Jana Ledvinová, Jakub Sikora, Ladislav Kuchař, Robert Dobrovolný
Mucopolysaccharidosis type II (MPSII) is a rare X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene (IDS, Xq28). MPSII is characterized by skeletal deformities, hearing loss, airway obstruction, hepatosplenomegaly, cardiac valvular disease, and progressive neurological impairment. At the cellular level, IDS deficiency leads to lysosomal storage of glycosaminoglycans (GAGs), dominated by accumulation of dermatan and heparan sulfates. Human induced pluripotent stem cells (iPSC) represent an alternative system that complements the available MPSII murine model...
November 22, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29163034/direct-reprogramming-rather-than-ipsc-based-reprogramming-maintains-aging-hallmarks-in-human-motor-neurons
#19
Yu Tang, Meng-Lu Liu, Tong Zang, Chun-Li Zhang
In vitro generation of motor neurons (MNs) is a promising approach for modeling motor neuron diseases (MNDs) such as amyotrophic lateral sclerosis (ALS). As aging is a leading risk factor for the development of neurodegeneration, it is important to recapitulate age-related characteristics by using MNs at pathogenic ages. So far, cell reprogramming through induced pluripotent stem cells (iPSCs) and direct reprogramming from primary fibroblasts are two major strategies to obtain populations of MNs. While iPSC generation must go across the epigenetic landscape toward the pluripotent state, directly converted MNs might have the advantage of preserving aging-associated features from fibroblast donors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29161257/regulation-of-camp-and-gsk3-signaling-pathways-contributes-to-the-neuronal-conversion-of-glioma
#20
Jinsoo Oh, Yongbo Kim, Lihua Che, Jeong Beom Kim, Gyeong Eon Chang, Eunji Cheong, Seok-Gu Kang, Yoon Ha
Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator)...
2017: PloS One
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