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https://www.readbyqxmd.com/read/27926491/early-pathogenic-event-of-alzheimer-s-disease-documented-in-ipscs-from-patients-with-psen1-mutations
#1
Juan Yang, Hanzhi Zhao, Yu Ma, Guilai Shi, Jian Song, Yu Tang, Song Li, Ting Li, Nan Liu, Fan Tang, Junjie Gu, Lingling Zhang, Zhuohua Zhang, Xiaohui Zhang, Ying Jin, Weidong Le
Alzheimer's disease (AD) is the most common age-related dementia characterized by progressive neuronal loss. However, the molecular mechanisms for the neuronal loss is still debated. Here, we used induced pluripotent stem cells (iPSCs) derived from somatic cells of familial AD patients carrying PSEN1 mutations to study the early pathogenic event of AD. We found that premature neuronal differentiation with decreased proliferation and increased apoptosis occured in AD-iPSC-derived neural progenitor cells (AD-NPCs) once neuronal differentiation was initiated, together with higher levels of Aβ42 and phosphorylated tau...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925861/modeling-heavy-ion-impairment-of-hippocampal-neurogenesis-after-acute-and-fractionated-irradiation
#2
Eliedonna Cacao, Francis A Cucinotta
Radiation-induced impairment of neurogenesis in the hippocampal dentate gyrus is a concern due to its reported association with cognitive detriments after radiotherapy for brain cancers and the possible risks to astronauts chronically exposed to space radiation. Here, we have extended our recent work in a mouse model of impaired neurogenesis after exposure to low-linear energy transfer (LET) heavy ion radiation. To our knowledge, this is the first report of a predictive mathematical model of radiation-induced changes to neurogenesis for a variety of radiation types after acute or fractionated irradiation...
December 7, 2016: Radiation Research
https://www.readbyqxmd.com/read/27925688/rare-deleterious-pard3-variants-in-the-apkc-binding-region-are-implicated-in-the-pathogenesis-of-human-cranial-neural-tube-defects-via-disrupting-apical-tight-junction-formation
#3
Xiaoli Chen, Yu An, Yonghui Gao, Liu Guo, Lei Rui, Hua Xie, Mei Sun, Siv Lam Hung, Xiaoming Sheng, Jizhen Zou, Yihua Bao, Hongyan Guan, Bo Niu, Zandong Li, Richard H Finnell, James F Gusella, Bai-Lin Wu, Ting Zhang
Increasing evidence that mutation of planar cell polarity (PCP) genes contributes to human cranial NTD susceptibility prompted us to hypothesize that rare variants of genes in the core apical-basal polarity (ABP) pathway are risk factors for cranial NTDs. In this study, we screened for rare genomic variation of PARD3 in 138 cranial NTD cases and 274 controls. Overall, the rare deleterious variants of PARD3 were significantly associated with increased risk for cranial NTDs (11/138 vs.7/274, p<0.05, OR = 3...
December 7, 2016: Human Mutation
https://www.readbyqxmd.com/read/27924849/transcriptional-regulation-of-notch1-expression-by-nkx6-1-in-neural-stem-progenitor-cells-during-ventral-spinal-cord-development
#4
Ying Li, Evangeline Tzatzalos, Kelvin Y Kwan, Martin Grumet, Li Cai
Notch1 signaling plays a critical role in maintaining and determining neural stem/progenitor cell (NSPC) fate, yet the transcriptional mechanism controlling Notch1 specific expression in NSPCs remains incomplete. Here, we show transcription factor Nkx6.1 interacts with a cis-element (CR2, an evolutionarily conserved non-coding fragment in the second intron of Notch1 locus) and regulates the expression of Notch1 in ventral NSPCs of the developing spinal cord. We show that the Notch1 expression is modulated by the interaction of Nkx6...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924017/a-genome-integrated-massively-parallel-reporter-assay-reveals-dna-sequence-determinants-of-cis-regulatory-activity-in-neural-cells
#5
Brett B Maricque, Joseph D Dougherty, Barak A Cohen
Recent large-scale genomics efforts to characterize the cis-regulatory sequences that orchestrate genome-wide expression patterns have produced impressive catalogues of putative regulatory elements. Most of these sequences have not been functionally tested, and our limited understanding of the non-coding genome prevents us from predicting which sequences are bona fide cis-regulatory elements. Recently, massively parallel reporter assays (MPRAs) have been deployed to measure the activity of putative cis-regulatory sequences in several biological contexts, each with specific advantages and distinct limitations...
October 23, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923664/arhgef1-is-expressed-in-cortical-neural-progenitor-cells-and-regulates-neurite-outgrowth-of-newly-differentiated-neurons
#6
Xiaoliang Xiang, Xiaoji Zhuang, Shengnan Li, Lei Shi
Neurite outgrowth is crucial for the maturation of neurons and the establishment of anatomical connections during development of the nervous system. We report here that Arhgef1, a RhoA guanine nucleotide exchange factor previously found expressed in the early stages of neuronal development to regulate neurite outgrowth, is also highly expressed in cortical neural progenitor cells (NPCs). To better dissect its role in NPCs, we knocked down Arhgef1 expression in these cells and induced differentiated of them into neurons...
December 3, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27923324/uncovering-the-in-vivo-source-of-adult-neural-crest-stem-cells
#7
Jorge B Aquino
Some late embryonic and adult postmigratory neural crest-derived cells (NCDCs) from diverse tissues were shown to grow as multipotent neurospheres. Neural crest stem cells (NCSCs) contained in these spheres, were found to give rise not only to neuroectodermal derivatives but also to some of the progeny of the other embryonic germ layers. In this review, evidences regarding the in vivo properties of NCDCs contributing to NCSCs are discussed. Even though in many cases the final prove for the phenotype identity of in vivo cells generating NCSCs is lacking, some evidences suggest that such postmigratory NCDCs would differ from neural crest cells (NCCs)...
December 6, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27920144/methyl-cpg-binding-protein-mbd1-regulates-neuronal-lineage-commitment-through-maintaining-adult-neural-stem-cell-identity
#8
Emily M Jobe, Yu Gao, Brian E Eisinger, Janessa K Mladucky, Charles C Giuliani, Laurel E Kelnhofer, Xinyu Zhao
: MBD1 belongs to a family of methyl-CpG binding proteins that are epigenetic "readers", linking DNA methylation to transcriptional regulation. MBD1 is expressed in neural stem cells residing in the dentate gyrus of the adult hippocampus (aNSCs), and MBD1 deficiency leads to reduced neuronal differentiation, impaired neurogenesis, learning deficits, and autism-like behaviors in mice; however the precise function of MBD1 in aNSCs remains unexplored. Here, we show that MBD1 is important for maintaining the integrity and stemness of NSCs, which is critical for their ability to generate neurons...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27918106/cannabidiol-activates-neuronal-precursor-genes-in-human-gingival-mesenchymal-stromal-cells
#9
Thangavelu Soundara Rajan, Sabrina Giacoppo, Domenico Scionti, Francesca Diomede, Gianpaolo Grassi, Federica Pollastro, Adriano Piattelli, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
In the last years, mesenchymal stromal cells (MSCs) from oral tissues have received considerable interest in regenerative medicine since they can be obtained with minimal invasive procedure and exhibit immunomodulatory properties. This study was aimed to investigate whether in vitro pre-treatment of MSCs obtained from human gingiva (hGMSCs) with Cannabidiol (CBD), a cannabinoid component produced by the plant Cannabis sativa, may promote human gingiva derived MSCs to differentiate towards neuronal precursor cells...
December 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27916527/dynamic-mrna-transport-and-local-translation-in-radial-glial-progenitors-of-the-developing-brain
#10
Louis-Jan Pilaz, Ashley L Lennox, Jeremy P Rouanet, Debra L Silver
In the developing brain, neurons are produced from neural stem cells termed radial glia [1, 2]. Radial glial progenitors span the neuroepithelium, extending long basal processes to form endfeet hundreds of micrometers away from the soma. Basal structures influence neuronal migration, tissue integrity, and proliferation [3-7]. Yet, despite the significance of these distal structures, their cell biology remains poorly characterized, impeding our understanding of how basal processes and endfeet influence neurogenesis...
November 30, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27915086/metabolism-and-neurogenesis
#11
REVIEW
Marlen Knobloch, Sebastian Jessberger
The generation of neurons in the developing and adult mammalian brain by neural stem/progenitor cells (NSPCs) depends on a tight control of NSPC activity and neuronal differentiation that is regulated by a plethora of intrinsic and extrinsic molecular cues. Besides well-studied morphogenic signaling pathways and transcriptional codes that govern the distinct developmental steps from the dividing NSPC to a functional neuron, a critical role of cellular metabolism to determine the functional properties of NSPCs and newborn neurons has been recently identified...
December 1, 2016: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/27912755/establishment-of-high-reciprocal-connectivity-between-clonal-cortical-neurons-is-regulated-by-the-dnmt3b-dna-methyltransferase-and-clustered-protocadherins
#12
Etsuko Tarusawa, Makoto Sanbo, Atsushi Okayama, Toshio Miyashita, Takashi Kitsukawa, Teruyoshi Hirayama, Takahiro Hirabayashi, Sonoko Hasegawa, Ryosuke Kaneko, Shunsuke Toyoda, Toshihiro Kobayashi, Megumi Kato-Itoh, Hiromitsu Nakauchi, Masumi Hirabayashi, Takeshi Yagi, Yumiko Yoshimura
BACKGROUND: The specificity of synaptic connections is fundamental for proper neural circuit function. Specific neuronal connections that underlie information processing in the sensory cortex are initially established without sensory experiences to a considerable extent, and then the connections are individually refined through sensory experiences. Excitatory neurons arising from the same single progenitor cell are preferentially connected in the postnatal cortex, suggesting that cell lineage contributes to the initial wiring of neurons...
December 2, 2016: BMC Biology
https://www.readbyqxmd.com/read/27912138/human-specific-genomic-signatures-of-neocortical-expansion
#13
REVIEW
Marta Florio, Víctor Borrell, Wieland B Huttner
Neocortex evolutionary expansion is primarily due to increased proliferative capacity of neural progenitor cells during cortical development. Exploiting insights into the cell biology of cortical progenitors gained during the past two decades, recent studies uncovered a variety of gene expression differences that underlie differential cortical progenitor behavior. These comprise both, differences between cortical areas that likely provide a molecular basis for cortical folding, and differences across species thought to be responsible for increases in neocortex size...
November 29, 2016: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/27912091/genetic-ablation-of-axl-does-not-protect-human-neural-progenitor-cells-and-cerebral-organoids-from-zika-virus-infection
#14
Michael F Wells, Max R Salick, Ole Wiskow, Daniel J Ho, Kathleen A Worringer, Robert J Ihry, Sravya Kommineni, Bilada Bilican, Joseph R Klim, Ellen J Hill, Liam T Kane, Chaoyang Ye, Ajamete Kaykas, Kevin Eggan
Zika virus (ZIKV) can cross the placental barrier, resulting in infection of the fetal brain and neurological defects including microcephaly. The cellular tropism of ZIKV and the identity of attachment factors used by the virus to gain access to key cell types involved in pathogenesis are under intense investigation. Initial studies suggested that ZIKV preferentially targets neural progenitor cells (NPCs), providing an explanation for the developmental phenotypes observed in some pregnancies. The AXL protein has been nominated as a key attachment factor for ZIKV in several cell types including NPCs...
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27912090/advances-in-zika-virus-research-stem-cell-models-challenges-and-opportunities
#15
REVIEW
Guo-Li Ming, Hengli Tang, Hongjun Song
The re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborns and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural progenitors and brain organoids, fetal tissues, and animal models. These efforts provided significant insight into cellular targets, pathogenesis, and underlying biological mechanisms of ZIKV infection as well as platforms for drug testing...
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27911758/multimodal-imaging-for-dreadd-expressing-neurons-in-living-brain-and-their-application-to-implantation-of-ipsc-derived-neural-progenitors
#16
Bin Ji, Hiroyuki Kaneko, Takafumi Minamimoto, Haruhisa Inoue, Hiroki Takeuchi, Katsushi Kumata, Ming-Rong Zhang, Ichio Aoki, Chie Seki, Maiko Ono, Masaki Tokunaga, Satoshi Tsukamoto, Koji Tanabe, Ryong-Moon Shin, Takeharu Minamihisamatsu, Seiji Kito, Barry J Richmond, Tetsuya Suhara, Makoto Higuchi
: Chemogenetic manipulation of neuronal activities has been enabled by a designer receptor (designer receptor exclusively activated by designer drugs, DREADD) that is activated exclusively by clozapine-N-oxide (CNO). Here, we applied CNO as a functional reporter probe to positron emission tomography (PET) of DREADD in living brains. Mutant human M4 DREADD (hM4Di) expressed in transgenic (Tg) mouse neurons was visualized by PET with microdose [(11)C]CNO. Deactivation of DREADD-expressing neurons in these mice by nonradioactive CNO at a pharmacological dose could also be captured by arterial spin labeling MRI (ASL-MRI)...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911741/neural-stem-cells-to-cerebral-cortex-emerging-mechanisms-regulating-progenitor-behavior-and-productivity
#17
Noelle D Dwyer, Bin Chen, Shen-Ju Chou, Simon Hippenmeyer, Laurent Nguyen, H Troy Ghashghaei
This review accompanies a 2016 SFN mini-symposium presenting examples of current studies that address a central question: How do neural stem cells (NSCs) divide in different ways to produce heterogeneous daughter types at the right time and in proper numbers to build a cerebral cortex with the appropriate size and structure? We will focus on four aspects of corticogenesis: cytokinesis events that follow apical mitoses of NSCs; coordinating abscission with delamination from the apical membrane; timing of neurogenesis and its indirect regulation through emergence of intermediate progenitors; and capacity of single NSCs to generate the correct number and laminar fate of cortical neurons...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27909687/morphogenesis-of-human-embryonic-stem-cells-into-mature-neurons-under-in-vitro-culture-conditions
#18
Geeta Shroff
AIM: To describe the morphogenesis of different neuronal cells from the human embryonic stem cell (hESC) line, SCT-N, under in vitro culture conditions. METHODS: The directed neuronal cell line was produced from a single, spare, pre-implantation stage fertilized ovum that was obtained during a natural in vitro fertilization process. The hESCs were cultured and maintained as per our proprietary in-house technology in a Good Manufacturing Practice, Good Laboratory Practice and Good Tissue Practice compliant laboratory...
November 20, 2016: World Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27908934/gata6-promotes-hair-follicle-progenitor-cell-renewal-by-genome-maintenance-during-proliferation
#19
Alex B Wang, Ying V Zhang, Tudorita Tumbar
Cell proliferation is essential to rapid tissue growth and repair, but can result in replication-associated genome damage. Here, we implicate the transcription factor Gata6 in adult mouse hair follicle regeneration where it controls the renewal of rapidly proliferating epithelial (matrix) progenitors and hence the extent of production of terminally differentiated lineages. We find that Gata6 protects against DNA damage associated with proliferation, thus preventing cell cycle arrest and apoptosis. Furthermore, we show that in vivo Gata6 stimulates EDA-receptor signaling adaptor Edaradd level and NF-κB pathway activation, known to be important for DNA damage repair and stress response in general and for hair follicle growth in particular...
December 1, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27908784/cisplatin-induced-mitochondrial-dysfunction-is-associated-with-impaired-cognitive-function-in-rats
#20
Naomi Lomeli, Kaijun Di, Jennifer Czerniawski, John F Guzowski, Daniela A Bota
PURPOSE: Chemotherapy-related cognitive impairment (CRCI) is commonly reported following the administration of chemotherapeutic agents and comprises a wide variety of neurological problems. No effective treatments for CRCI are currently available. Here we examined the mechanisms involving cisplatin-induced hippocampal damage following cisplatin administration in a rat model and in cultured rat hippocampal neurons and neural stem/progenitor cells (NSC). We also assessed the protective effects of the antioxidant, N-acetylcysteine in mitigating these damages...
November 28, 2016: Free Radical Biology & Medicine
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