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https://www.readbyqxmd.com/read/28346452/purine-synthesis-promotes-maintenance-of-brain-tumor-initiating-cells-in-glioma
#1
Xiuxing Wang, Kailin Yang, Qi Xie, Qiulian Wu, Stephen C Mack, Yu Shi, Leo J Y Kim, Briana C Prager, William A Flavahan, Xiaojing Liu, Meromit Singer, Christopher G Hubert, Tyler E Miller, Wenchao Zhou, Zhi Huang, Xiaoguang Fang, Aviv Regev, Mario L Suvà, Tae Hyun Hwang, Jason W Locasale, Shideng Bao, Jeremy N Rich
Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake active normally in neurons to maintain energy demands. Here we link metabolic dysregulation in human BTICs to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28345605/extracellular-matrix-protein-reelin-promotes-myeloma-progression-by-facilitating-tumor-cell-proliferation-and-glycolysis
#2
Xiaodan Qin, Liang Lin, Li Cao, Xinwei Zhang, Xiao Song, Jie Hao, Yan Zhang, Risheng Wei, Xiaojun Huang, Jin Lu, Qing Ge
Reelin is an extracellular matrix protein that is crucial for neuron migration, adhesion, and positioning. We examined the expression of Reelin in a large cohort of multiple myeloma patients recorded in Gene Expression Omnibus (GEO) database and used over-expression and siRNA knockdown of Reelin to investigate the role of Reelin in myeloma cell growth. We find that Reelin expression is negatively associated with myeloma prognosis. Reelin promotes myeloma cell proliferation in vitro as well as in vivo. The Warburg effect, evidenced by increased glucose uptake and lactate production, is also enhanced in Reelin-expressing cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344001/inducible-and-deterministic-forward-programming-of-human-pluripotent-stem-cells-into-neurons-skeletal-myocytes-and-oligodendrocytes
#3
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...
March 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28339833/vdac1-is-a-molecular-target-in-glioblastoma-with-its-depletion-leading-to-reprogrammed-metabolism-and-reversed-oncogenic-properties
#4
Tasleem Arif, Yakov Kerlin, Itay Nakdimon, Daniel Benharroch, Avijit Paul, Daniela Dadon-Klein, Varda Shoshan-Barmatz
Background.: Glioblastoma (GBM), an aggressive brain tumor with frequent relapses and a high mortality, still awaits an effective treatment. Like many cancers, GBM cells acquire oncogenic properties, including metabolic reprogramming, vital for growth. As such, tumor metabolism is an emerging avenue for cancer therapy. One relevant target is the voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein controlling cell energy and metabolic homeostasis. Methods...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28336360/gain-a-graph-based-method-to-automatically-analyze-neurite-outgrowth-in-cell-cultures
#5
B L Long, H Li, A Mahadevan, T Tang, K Balotin, N Grandel, J Soto, S Y Wong, A Abrego, S Li, A A Qutub
BACKGROUND: Neurite outgrowth is a metric widely used to assess the success of in vitro neural stem cell differentiation or neuron reprogramming protocols and of high-content screening assays for neural regenerative drug discovery. However, neurite measurements are tedious to perform manually, and there is a paucity of freely available, fully automated software to determine neurite measurements and neuron counting. To provide such a tool to the neurobiology, stem cell, cell engineering, and neuroregenerative communities, we developed an algorithm for performing high-throughput neurite analysis in immunofluorescence images...
March 20, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28333692/application-of-olfactory-tissue-and-its-neural-progenitors-to-schizophrenia-and-psychiatric-research
#6
Joëlle Lavoie, Akira Sawa, Koko Ishizuka
PURPOSE OF REVIEW: The goal of this review article is to introduce olfactory epithelium-derived cell/tissue models as a promising surrogate system to study the molecular mechanisms implicated in schizophrenia and other neuropsychiatric disorders. Here, we particularly focus on the utility of their neural progenitors. RECENT FINDINGS: Recent investigations of the pathophysiology of schizophrenia using olfactory epithelium-derived tissue/cell models have provided insights about schizophrenia-associated alterations in neurodevelopment, stress response, and gene/protein expression regulatory pathways...
March 22, 2017: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/28327614/partial-reprogramming-of-pluripotent-stem-cell-derived-cardiomyocytes-into-neurons
#7
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
#8
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/28302722/amyloid-%C3%AE-oligomers-transiently-inhibit-amp-activated-kinase-and-cause-metabolic-defects-in-hippocampal-neurons
#9
Gisele S Seixas da Silva, Helen M Melo, Mychael V Lourenco, Natalia de M Lyra E Silva, Marcelo B de Carvalho, Soniza Alves-Leon, Jorge M de Souza, William L Klein, Wagner S da-Silva, Sergio T Ferreira, Fernanda G De Felice
AMP-activated kinase (AMPK) is a key player in energy sensing and metabolic reprogramming under cellular energy restriction. Several studies have linked impaired AMPK function to peripheral metabolic diseases such as diabetes. However, the impact of neurological disorders, such as Alzheimer disease (AD), on AMPK function and downstream effects of altered AMPK activity on neuronal metabolism have been investigated only recently. Here, we report the impact of A β oligomers (AβOs), synaptotoxins that accumulate in AD brains, on neuronal AMPK activity...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28293168/modeling-human-neurological-and-neurodegenerative-diseases-from-induced-pluripotent-stem-cells-to-neuronal-differentiation-and-its-applications-in-neurotrauma
#10
REVIEW
Hisham Bahmad, Ola Hadadeh, Farah Chamaa, Katia Cheaito, Batoul Darwish, Ahmad-Kareem Makkawi, Wassim Abou-Kheir
With the help of several inducing factors, somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) lines. The success is in obtaining iPSCs almost identical to embryonic stem cells (ESCs), therefore various approaches have been tested and ultimately several ones have succeeded. The importance of these cells is in how they serve as models to unveil the molecular pathways and mechanisms underlying several human diseases, and also in its potential roles in the development of regenerative medicine...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28279785/epigenetic-interventions-for-epileptogenesis-a-new-frontier-for-curing-epilepsy
#11
REVIEW
Iyan Younus, Doodipala Samba Reddy
This article highlights the emerging therapeutic potential of specific epigenetic modulators as promising antiepileptogenic or disease-modifying agents for curing epilepsy. Currently, there is an unmet need for antiepileptogenic agents that truly prevent the development of epilepsy in people at risk. There is strong evidence that epigenetic signaling, which exerts high fidelity regulation of gene expression, plays a crucial role in the pathophysiology of epileptogenesis and chronic epilepsy. These modifications are not hard-wired into the genome and are constantly reprogrammed by environmental influences...
March 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28262173/cellular-models-to-study-schizophrenia-a-systematic-review
#12
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/28259862/-modeling-neurological-and-psychiatric-disorders-in-vitro-using-induced-pluripotent-stem-cells-highlighting-findings-in-alzheimer-s-disease-and-schizophrenia
#13
Edit Hathy, Sara Kalman, Agota Apati, Zsofia Nemoda, Janos M Rethelyi
Over the past decade we witnessed the birth of a new scientific area that lies at the borders of developmental biology, stem cell biology, basic and clinical neuroscience. In vitro disease modeling refers to the approach that exploits the capacity of stem cells for self-renewal and pluripotency by generating specific cell types that are relevant for a given disorder. Based on this method, neurological and psychiatric disorders can be investigated by differentiating stem cells into neurons in a dish, and studying the relevant neuronal populations affected in the pathophysiology of the disorder in terms of specific cellular phenotypes...
December 2016: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/28238659/the-cdk8-complex-and-proneural-proteins-together-drive-neurogenesis-from-a-mesodermal-lineage
#14
Shuo Luo, H Robert Horvitz
At least some animal species can generate neurons from mesoderm or endoderm, but the underlying mechanisms remain unknown. We screened for C. elegans mutants in which the presumptive mesoderm-derived I4 neuron adopts a muscle-like cell fate. From this screen, we identified HLH-3, the C. elegans homolog of a mammalian proneural protein (Ascl1) used for in vitro neuronal reprogramming, as required for efficient I4 neurogenesis. We discovered that the CDK-8 Mediator kinase module acts together with a second proneural protein, HLH-2, and in parallel to HLH-3 to promote I4 neurogenesis...
March 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28230276/dissection-of-regulatory-elements-during-direct-conversion-of-somatic-cells-into-neurons
#15
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/28229087/modeling-williams-syndrome-with-induced-pluripotent-stem-cells
#16
Thanathom Chailangkarn, Alysson R Muotri
The development of induced pluripotent stem cells (iPSCs) like never before has opened novel opportunity to study diseases in relevant cell types. In our recent study, Williams syndrome (WS), a rare genetic neurodevelopmental disorder, that is caused by hemizygous deletion of 25-28 genes on chromosome 7, is of interest because of its unique cognitive and social profiles. Little is known about haploinsufficiency effect of those deleted genes on molecular and cellular phenotypes at the neural level due to the lack of relevant human cellular model...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28216149/direct-generation-of-human-neuronal-cells-from-adult-astrocytes-by-small-molecules
#17
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/28216148/epigenetic-modification-of-the-ccl5-ccr1-erk-axis-enhances-glioma-targeting-in-dedifferentiation-reprogrammed-bmscs
#18
Rui Chen, Wayne Yuk-Wai Lee, Xiao Hu Zhang, Jie Ting Zhang, Sien Lin, Liang Liang Xu, Biao Huang, Fu Yuan Yang, Hai Long Liu, Bin Wang, Lai Ling Tsang, Sandrine Willaime-Morawek, Gang Li, Hsiao Chang Chan, Xiaohua Jiang
The success of stem cell-mediated gene therapy in cancer treatment largely depends on the specific homing ability of stem cells. We have previously demonstrated that after in vitro induction of neuronal differentiation and dedifferentiation, bone marrow stromal cells (BMSCs) revert to a primitive stem cell population (De-neu-BMSCs) distinct from naive BMSCs. We report here that De-neu-BMSCs express significantly higher levels of chemokines, and display enhanced homing abilities to glioma, the effect of which is mediated by the activated CCL5/CCR1/ERK axis...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28216145/a-human-neural-crest-stem-cell-derived-dopaminergic-neuronal-model-recapitulates-biochemical-abnormalities-in-gba1-mutation-carriers
#19
Shi-Yu Yang, Michelle Beavan, Kai-Yin Chau, Jan-Willem Taanman, Anthony H V Schapira
Numerically the most important risk factor for the development of Parkinson's disease (PD) is the presence of mutations in the glucocerebrosidase GBA1 gene. In vitro and in vivo studies show that GBA1 mutations reduce glucocerebrosidase (GCase) activity and are associated with increased α-synuclein levels, reflecting similar changes seen in idiopathic PD brain. We have developed a neural crest stem cell-derived dopaminergic neuronal model that recapitulates biochemical abnormalities in GBA1 mutation-associated PD...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28213718/reprogramming-cell-fates-by-small-molecules
#20
REVIEW
Xiaojie Ma, Linghao Kong, Saiyong Zhu
Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our understanding of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on reprogramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for various applications, such as disease modeling and cell-based transplantation, but also hold great promise to be further developed as drugs to stimulate patients' endogenous cells to repair and regenerate in vivo...
February 17, 2017: Protein & Cell
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