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https://www.readbyqxmd.com/read/29147115/effects-of-aminoglycoside-antibiotics-on-human-embryonic-stem-cell-viability-during-differentiation-in-vitro
#1
Divya S Varghese, Shama Parween, Mustafa T Ardah, Bright Starling Emerald, Suraiya A Ansari
Human embryonic stem cells (hESCs) are being used extensively in array of studies to understand different mechanisms such as early human embryogenesis, drug toxicity testing, disease modeling, and cell replacement therapy. The protocols for the directed differentiation of hESCs towards specific cell types often require long-term cell cultures. To avoid bacterial contamination, these protocols include addition of antibiotics such as pen-strep and gentamicin. Although aminoglycosides, streptomycin, and gentamicin have been shown to cause cytotoxicity in various animal models, the effect of these antibiotics on hESCs is not clear...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29056334/functional-antagonism-between-otx2-and-nanog-specifies-a-spectrum-of%C3%A2-heterogeneous-identities-in-embryonic-stem-cells
#2
Dario Acampora, Luca Giovanni Di Giovannantonio, Arcomaria Garofalo, Vincenzo Nigro, Daniela Omodei, Alessia Lombardi, Jingchao Zhang, Ian Chambers, Antonio Simeone
Embryonic stem cells (ESCs) cultured in leukemia inhibitory factor (LIF) plus fetal bovine serum (FBS) exhibit heterogeneity in the expression of naive and primed transcription factors. This heterogeneity reflects the dynamic condition of ESCs and their versatility to promptly respond to signaling effectors promoting naive or primed pluripotency. Here, we report that ESCs lacking Nanog or overexpressing Otx2 exhibit an early primed identity in LIF + FBS and fail to convert into 2i-induced naive state. Conversely, Otx2-null ESCs possess naive identity features in LIF + FBS similar to Nanog-overexpressing ESCs and convert poorly into FGF-induced early primed state...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29038581/transcriptional-repression-of-plxnc1-by-lmx1a-and-lmx1b-directs-topographic-dopaminergic-circuit-formation
#3
Audrey Chabrat, Guillaume Brisson, Hélène Doucet-Beaupré, Charleen Salesse, Marcos Schaan Profes, Axelle Dovonou, Cléophace Akitegetse, Julien Charest, Suzanne Lemstra, Daniel Côté, R Jeroen Pasterkamp, Monica I Abrudan, Emmanouil Metzakopian, Siew-Lan Ang, Martin Lévesque
Mesodiencephalic dopamine neurons play central roles in the regulation of a wide range of brain functions, including voluntary movement and behavioral processes. These functions are served by distinct subtypes of mesodiencephalic dopamine neurons located in the substantia nigra pars compacta and the ventral tegmental area, which form the nigrostriatal, mesolimbic, and mesocortical pathways. Until now, mechanisms involved in dopaminergic circuit formation remained largely unknown. Here, we show that Lmx1a, Lmx1b, and Otx2 transcription factors control subtype-specific mesodiencephalic dopamine neurons and their appropriate axon innervation...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29031852/inhibition-of-cdk5-rejuvenates-inhibitory-circuits-and-restores-experience-dependent-plasticity-in-adult-visual-cortex
#4
Yue Li, Laijian Wang, Xinxin Zhang, Mengyao Huang, Sitong Li, Xinxing Wang, Lin Chen, Bin Jiang, Yupeng Yang
Cyclin-dependent kinase 5 (Cdk5) acts as an essential modulator for neural development and neurological disorders. Here we show that Cdk5 plays a pivotal role in modulating GABAergic signaling and the maturation of visual system. In adult mouse primary visual cortex, Cdk5 formed complex with the GABA synthetic enzyme glutamate decarboxylase GAD67, but not with GAD65. In addition to enhancement in the surface level of NR2B-containing NMDA receptors, inhibition of Cdk5 reduced the protein levels of GADs and Otx2, while leaving intact the expression of vesicular GABA transporter and subunits of GABAA or AMPA receptors...
October 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29028809/nasal-dna-methylation-differentiates-corticosteroid-treatment-response-in-pediatric-asthma-a-pilot-study
#5
Xue Zhang, Jocelyn M Biagini Myers, Veda K Yadagiri, Ashley Ulm, Xiaoting Chen, Matthew T Weirauch, Gurjit K Khurana Hershey, Hong Ji
BACKGROUND: Treatment response to systemic corticosteroid in asthmatic children is heterogeneous and may be mediated by epigenetic mechanism(s). We aim to identify DNA methylation (DNAm) changes responsive to steroid, and DNAm biomarkers that distinguish treatment response. MATERIALS AND METHODS: We followed 33 children (ages 5-18) presenting to the Emergency Department (ED) for asthma exacerbation. Based on whether they met discharge criteria in ≤24 hours, participants were grouped into good and poor responders to steroid treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28988713/otx2-genetically-modified-retinal-pigment-epithelial-cells-rescue-photoreceptors-after-transplantation
#6
Christo Kole, Laurence Klipfel, Ying Yang, Vanessa Ferracane, Frederic Blond, Sacha Reichman, Géraldine Millet-Puel, Emmanuelle Clérin, Najate Aït-Ali, Delphine Pagan, Hawa Camara, Marie-Noëlle Delyfer, Emeline F Nandrot, Jose-Alain Sahel, Olivier Goureau, Thierry Léveillard
Inherited retinal degenerations are blinding diseases characterized by the loss of photoreceptors. Their extreme genetic heterogeneity complicates treatment by gene therapy. This has motivated broader strategies for transplantation of healthy retinal pigmented epithelium to protect photoreceptors independently of the gene causing the disease. The limited clinical benefit for visual function reported up to now is mainly due to dedifferentiation of the transplanted cells that undergo an epithelial-mesenchymal transition...
September 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28974755/chondroitin-sulfate-is-required-for-onset-and-offset-of-critical-period-plasticity-in-visual-cortex
#7
Xubin Hou, Nozomu Yoshioka, Hiroaki Tsukano, Akiko Sakai, Shinji Miyata, Yumi Watanabe, Yuchio Yanagawa, Kenji Sakimura, Kosei Takeuchi, Hiroshi Kitagawa, Takao K Hensch, Katsuei Shibuki, Michihiro Igarashi, Sayaka Sugiyama
Ocular dominance plasticity is easily observed during the critical period in early postnatal life. Chondroitin sulfate (CS) is the most abundant component in extracellular structures called perineuronal nets (PNNs), which surround parvalbumin-expressing interneurons (PV-cells). CS accumulates in PNNs at the critical period, but its function in earlier life is unclear. Here, we show that initiation of ocular dominance plasticity was impaired with reduced CS, using mice lacking a key CS-synthesizing enzyme, CSGalNAcT1...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28861107/piwi-like-protein-hiwi2-is-aberrantly-expressed-in-retinoblastoma-cells-and-affects-cell-cycle-potentially-through-otx2
#8
Suganya Sivagurunathan, Jayamuruga Pandian Arunachalam, Subbulakshmi Chidambaram
Retinoblastoma (RB), a childhood cancer, is caused by biallelic mutation of the RB1 gene, but its development is not clearly understood. Furthermore, the presence of a cancer stem cell subpopulation in RB might impact its treatment. PIWI protein, known for its role in stem cell self-renewal, is aberrantly expressed in cancers. We examined the role of the PIWI-like protein HIWI2 in RB and its effect on the stem cell markers in cells of the RB line, Y79. The expression of HIWI2 is significantly increased in Y79 compared with its level in HeLa and ARPE19 cells...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28853082/reprogramming-of-human-retinal-pigment-epithelial-cells-under-the-effect-of-bfgf-in-vitro
#9
E V Shafei, A M Kurinov, A V Kuznetsova, M A Aleksandrova
We studied the effect of bFGF on human retinal pigment epithelial cells in vitro In ARPE-19 cells, enhanced expression of KLF4 mRNA and reduced expression of PAX6, MITF, and OTX2 mRNA specific for retinal pigment epithelium were observed after bFGF application. The expression of KLF4 mRNA peaked in 72 h after bFGF application and then sharply decreased, which was accompanied by a 3-fold increase in TUBB3 mRNA expression (neuronal marker). Immunocytochemical analysis showed that in the presence of bFGF, some cells retained epithelial properties and showed positive staining for connexin-43, while others had long axon-like processes and demonstrated positive staining for βIII-tubulin, which attests to their neuronal transdifferentiation...
August 29, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28829770/combinatorial-regulation-of-a-blimp1-prdm1-enhancer-in-the-mouse-retina
#10
Taylor S Mills, Tatiana Eliseeva, Stephanie M Bersie, Grace Randazzo, Jhenya Nahreini, Ko Uoon Park, Joseph A Brzezinski
The mouse retina comprises seven major cell types that exist in differing proportions. They are generated from multipotent progenitors in a stochastic manner, such that the relative frequency of any given type generated changes over time. The mechanisms determining the proportions of each cell type are only partially understood. Photoreceptors and bipolar interneurons are derived from cells that express Otx2. Within this population, Blimp1 (Prdm1) helps set the balance between photoreceptors and bipolar cells by suppressing bipolar identity in most of the cells...
2017: PloS One
https://www.readbyqxmd.com/read/28814475/developmental-pathway-genes-and-neural-plasticity-underlying-emotional-learning-and-stress-related-disorders
#11
Marissa E Maheu, Kerry J Ressler
The manipulation of neural plasticity as a means of intervening in the onset and progression of stress-related disorders retains its appeal for many researchers, despite our limited success in translating such interventions from the laboratory to the clinic. Given the challenges of identifying individual genetic variants that confer increased risk for illnesses like depression and post-traumatic stress disorder, some have turned their attention instead to focusing on so-called "master regulators" of plasticity that may provide a means of controlling these potentially impaired processes in psychiatric illnesses...
September 2017: Learning & Memory
https://www.readbyqxmd.com/read/28807725/the-rnf146-e3-ubiquitin-ligase-is-required-for-the-control-of-wnt-signaling-and-body-pattern-formation-in-xenopus
#12
Xuechen Zhu, Rui Xing, Renbo Tan, Rongyang Dai, Qinghua Tao
The RING finger protein Rnf146 encodes an E3 ubiquitin ligase capable of targeting poly-ADP-ribosylated substrates for proteasomal degradation. Rnf146 has been identified as a critical regulator of Axin1 and thus of Wnt/β-catenin signaling. However its physiological significance in vertebrate embryonic development remains to be demonstrated. In this study, we take advantages of early Xenopus embryos to demonstrate that Rnf146 is essential for embryonic pattern formation. Depletion of zygotic Rnf146 using a translation blocking morpholino oligo (MO) results in anteriorized development and increased expression the anterior marker gene Otx2, consistent the notion that Rnf146 is a positive regulator of Wnt/β-catenin signaling through negatively regulating Axin1 expression...
October 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28800615/pitx3-and-en1-determine-the-size-and-molecular-programming-of-the-dopaminergic-neuronal-pool
#13
Willemieke M Kouwenhoven, Lars von Oerthel, Marten P Smidt
Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28779972/critical-role-of-trpc1-in-thyroid-hormone-dependent-dopaminergic-neuron-development
#14
Chunhai Chen, Qinglong Ma, Ping Deng, Jianjing Yang, Lingling Yang, Min Lin, Zhengping Yu, Zhou Zhou
Thyroid hormones play a crucial role in midbrain dopaminergic (DA) neuron development. However, the underlying molecular mechanisms remain largely unknown. In this study, we revealed that thyroid hormone treatment evokes significant calcium entry through canonical transient receptor potential (TRPC) channels in ventral midbrain neural stem cells and this calcium signaling is essential for thyroid hormone-dependent DA neuronal differentiation. We also found that TRPC1 is the dominant TRPC channel expressed in ventral midbrain neural stem cells which responds to thyroid hormone...
August 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28713249/crispr-cas9-mediated-zebrafish-knock-in-as-a-novel-strategy-to-study-midbrain-hindbrain-boundary-development
#15
Gokul Kesavan, Avinash Chekuru, Anja Machate, Michael Brand
The midbrain-hindbrain boundary (MHB) acts as an organizer and controls the fate of neighboring cells to develop into either mesencephalic (midbrain) or metencephalic (hindbrain) cells by secreting signaling molecules like Wnt1 and Fgf8. The zebrafish is an excellent vertebrate model for studying MHB development due to the ease of gene manipulation and the possibility of following cellular dynamics and morphogenetic processes using live imaging. Currently, only very few reporter and/or Cre-driver lines are available to study gene expression at the MHB, hampering the understanding of MHB development, and traditional transgenic technologies using promoter/enhancer fragments or bacterial artificial chromosome (BAC)-mediated transgenesis often do not faithfully recapitulate endogenous expression patterns...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#16
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina E Emborg, Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter life span compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties, including the development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
September 1, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28620275/genome-wide-target-analyses-of-otx2-homeoprotein-in-postnatal-cortex
#17
Akiko Sakai, Ryuichiro Nakato, Yiwei Ling, Xubin Hou, Norikazu Hara, Tomoya Iijima, Yuchio Yanagawa, Ryozo Kuwano, Shujiro Okuda, Katsuhiko Shirahige, Sayaka Sugiyama
Juvenile brain has a unique time window, or critical period, in which neuronal circuits are remodeled by experience. Mounting evidence indicates the importance of neuronal circuit rewiring in various neurodevelopmental disorders of human cognition. We previously showed that Otx2 homeoprotein, essential for brain formation, is recaptured during postnatal maturation of parvalbumin-positive interneurons (PV cells) to activate the critical period in mouse visual cortex. Cortical Otx2 is the only interneuron-enriched transcription factor known to regulate the critical period, but its downstream targets remain unknown...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28619944/early-life-stress-confers-lifelong-stress-susceptibility-in-mice-via-ventral-tegmental-area-otx2
#18
Catherine J Peña, Hope G Kronman, Deena M Walker, Hannah M Cates, Rosemary C Bagot, Immanuel Purushothaman, Orna Issler, Yong-Hwee Eddie Loh, Tin Leong, Drew D Kiraly, Emma Goodman, Rachael L Neve, Li Shen, Eric J Nestler
Early life stress increases risk for depression. Here we establish a "two-hit" stress model in mice wherein stress at a specific postnatal period increases susceptibility to adult social defeat stress and causes long-lasting transcriptional alterations that prime the ventral tegmental area (VTA)-a brain reward region-to be in a depression-like state. We identify a role for the developmental transcription factor orthodenticle homeobox 2 (Otx2) as an upstream mediator of these enduring effects. Transient juvenile-but not adult-knockdown of Otx2 in VTA mimics early life stress by increasing stress susceptibility, whereas its overexpression reverses the effects of early life stress...
June 16, 2017: Science
https://www.readbyqxmd.com/read/28612405/a-comparative-transcriptomic-analysis-of-development-in-two-astyanax-cavefish-populations
#19
Bethany A Stahl, Joshua B Gross
Organisms that are isolated into extreme environments often evolve extreme phenotypes. However, global patterns of dynamic gene expression changes that accompany dramatic environmental changes remain largely unknown. The blind Mexican cavefish, Astyanax mexicanus, has evolved a number of severe cave-associated phenotypes including loss of vision and pigmentation, craniofacial bone fusions, increased fat storage, reduced sleep, and amplified nonvisual sensory systems. Interestingly, surface-dwelling forms have repeatedly entered different caves throughout Mexico, providing a natural set of "replicate" instances of cave isolation...
September 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/28575744/decreased-neural-precursor-cell-pool-in-nadph-oxidase-2-deficiency-from-mouse-brain-to-neural-differentiation-of-patient-derived-ipsc
#20
Zeynab Nayernia, Marilena Colaianna, Natalia Robledinos-Antón, Eveline Gutzwiller, Frédérique Sloan-Béna, Elisavet Stathaki, Yousef Hibaoui, Antonio Cuadrado, Jürgen Hescheler, Marie-José Stasia, Tomo Saric, Vincent Jaquet, Karl-Heinz Krause
There is emerging evidence for the involvement of reactive oxygen species (ROS) in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD) patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC). High levels of NOX2 were found in mouse adult neurogenic regions...
April 24, 2017: Redox Biology
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