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https://www.readbyqxmd.com/read/28297587/efficiently-specified-ventral-midbrain-dopamine-neurons-from-human-pluripotent-stem-cells-under-xeno-free-conditions-restore-motor-deficits-in-parkinsonian-rodents
#1
Jonathan C Niclis, Carlos W Gantner, Walaa F Alsanie, Stuart J McDougall, Chris R Bye, Andrew G Elefanty, Edouard G Stanley, John M Haynes, Colin W Pouton, Lachlan H Thompson, Clare L Parish
Recent studies have shown evidence for the functional integration of human pluripotent stem cell (hPSC)-derived ventral midbrain dopamine (vmDA) neurons in animal models of Parkinson's disease. Although these cells present a sustainable alternative to fetal mesencephalic grafts, a number of hurdles require attention prior to clinical translation. These include the persistent use of xenogeneic reagents and challenges associated with scalability and storage of differentiated cells. In this study, we describe the first fully defined feeder- and xenogeneic-free protocol for the generation of vmDA neurons from hPSCs and utilize two novel reporter knock-in lines (LMX1A-eGFP and PITX3-eGFP) for in-depth in vitro and in vivo tracking...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28288836/temporal-profiling-of-photoreceptor-lineage-gene-expression-during-murine-retinal-development
#2
Tooka Aavani, Nobuhiko Tachibana, Valerie Wallace, Jeffrey Biernaskie, Carol Schuurmans
Rod and cone photoreceptors are photosensitive cells in the retina that convert light to electrical signals that are transmitted to visual processing centres in the brain. During development, cones and rods are generated from a common pool of multipotent retinal progenitor cells (RPCs) that also give rise to other retinal cell types. Cones and rods differentiate in two distinct waves, peaking in mid-embryogenesis and the early postnatal period, respectively. As RPCs transition from making cones to generating rods, there are changes in the expression profiles of genes involved in photoreceptor cell fate specification and differentiation...
March 10, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28285945/hanging-drop-culture-enhances-differentiation-of-human-adipose-derived-stem-cells-into-anterior-neuroectodermal-cells-using-small-molecules
#3
Noushin Amirpour, Shahnaz Razavi, Ebrahim Esfandiari, Batoul Hashemibeni, Mohammad Kazemi, Hossein Salehi
Inspired by in vivo developmental process, several studies were conducted to design a protocol for differentiating of mesenchymal stem cells into neural cells in vitro. Human adipose-derived stem cells (hADSCs) as mesenchymal stem cells are a promising source for this purpose. At current study, we applied a defined neural induction medium by using small molecules for direct differentiation of hADSCs into anterior neuroectodermal cells. Anterior neuroectodermal differentiation of hADSCs was performed by hanging drop and monolayer protocols...
March 7, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28256796/human-limbal-neurospheres-prevent-photoreceptor-cell-death-in-a-rat-model-of-retinal-degeneration
#4
Samuel McLenachan, Dan Zhang, Erwei Hao, Ling Zhang, Shang-Chih Chen, Fred K Chen
BACKGROUND: The culture of retinal progenitors from an accessible adult stem cell source such as the limbus could provide a useful autologous source of retinal cell therapies. The human corneoscleral limbus contains multipotent stem cells that can be cultured as floating neurospheres. Previous work in rodents has demonstrated neuronal and photoreceptor differentiation from limbal neurosphere cultures. Here, we have examined undifferentiated cultured adult human limbal neurospheres as donor cells for retinal cell therapies by transplantation into a rat model of retinal degeneration...
March 3, 2017: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/28246173/nutrient-driven-o-glcnac-cycling-impacts-neurodevelopmental-timing-and-metabolism
#5
Stephanie Olivier-Van Stichelen, Peng Wang, Marcy Comly, Dona C Love, John A Hanover
Nutrient-driven O-GlcNAcylation is strikingly abundant in the brain and has been linked to development and neurodegenerative disease. We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. The brain-knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes including early onset obesity, growth defects, and metabolic dysregulation. Anatomical defects in the Oga knockout included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay...
February 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28219951/generation-of-thalamic-neurons-from-mouse-embryonic-stem-cells
#6
Atsushi Shiraishi, Keiko Muguruma, Yoshiki Sasai
Thalamus is a diencephalic structure that plays crucial roles in relaying and modulating sensory and motor information to the neocortex. The thalamus develops in the dorsal part of the neural tube at the level of the caudal forebrain. However, the molecular mechanisms that are essential for thalamic differentiation are still unknown. Here we have succeeded in the generation of thalamic neurons from mouse ES cells (mESCs) by modifying the default method that induces the most-anterior neural type in self-organizing culture...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#7
Gaylor Boulay, Mary E Awad, Nicolo Riggi, Tenley C Archer, Sowmya Iyer, Wannaporn E Boonseng, Nikki E Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C Kim, Jill P Mesirov, Pablo Tamayo, Scott L Pomeroy, Martin J Aryee, Miguel N Rivera
Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1...
March 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28194008/genetic-otx2-mis-localization-delays-critical-period-plasticity-across-brain-regions
#8
H H C Lee, C Bernard, Z Ye, D Acampora, A Simeone, A Prochiantz, A A Di Nardo, T K Hensch
Accumulation of non-cell autonomous Otx2 homeoprotein in postnatal mouse visual cortex (V1) has been implicated in both the onset and closure of critical period (CP) plasticity. Here, we show that a genetic point mutation in the glycosaminoglycan recognition motif of Otx2 broadly delays the maturation of pivotal parvalbumin-positive (PV+) interneurons not only in V1 but also in the primary auditory (A1) and medial prefrontal cortex (mPFC). Consequently, not only visual, but also auditory plasticity is delayed, including the experience-dependent expansion of tonotopic maps in A1 and the acquisition of acoustic preferences in mPFC, which mitigates anxious behavior...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28154013/nitric-oxide-regulates-homeoprotein-otx1-and-otx2-expression-in-the-rat-myenteric-plexus-after-intestinal-ischemia-reperfusion-injury
#9
Viviana Filpa, Elisa Carpanese, Silvia Marchet, Cristina Pirrone, Andrea Conti, Alessia Rainero, Elisabetta Moro, Anna Maria Chiaravalli, Ileana Zucchi, Andrea Moriondo, Daniela Negrini, Francesca Crema, Gianmario Frigo, Cristina Giaroni, Giovanni Porta
Neuronal and inducible NO synthase (nNOS and iNOS) play a protective and damaging role, respectively, on the intestinal neuromuscular function after ischemia and reperfusion (I/R) injury. To uncover the molecular pathways underlying this dichotomy we investigated their possible correlation with orthodenticle homeobox proteins OTX1 and OTX2 in the rat small intestine myenteric plexus after in vivo I/R. Homeobox genes are fundamental for the regulation of the gut wall homeostasis both during development and in pathological conditions (inflammation, cancer)...
February 2, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28124402/knock-in-strategy-at-3-end-of-crx-gene-by-crispr-cas9-system-shows-the-gene-expression-profiles-during-human-photoreceptor-differentiation
#10
Kohei Homma, Sumiko Usui, Makoto Kaneda
Fluorescent reporter gene knock-in induced pluripotent stem cell (iPSC) lines have been used to evaluate the efficiency of differentiation into specific cell lineages. Here, we report a knock-in strategy for the generation of human iPSC reporter lines in which a 2A peptide sequence and a red fluorescent protein (E2-Crimson) gene were inserted at the termination codon of the cone-rod homeobox (Crx) gene, a photoreceptor-specific transcriptional factor gene. The knock-in iPSC lines were differentiated into fluorescence-expressing cells in 3D retinal differentiation culture, and the fluorescent cells also expressed Crx specifically in the nucleus...
January 26, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28118667/restoration-of-mesenchymal-rpe-by-transcription-factor-mediated-reprogramming
#11
Ying-Hsuan Shih, Monte J Radeke, Carolyn M Radeke, Pete J Coffey
Purpose: Transforming growth factor β-mediated epithelial-to-mesenchymal transition (EMT) is a major component of the wound healing response and a negative determinant of retinal pigment epithelium (RPE) differentiation. We have shown previously that inhibition of TGFβ signaling restored the capacity of mesenchymal RPE to differentiate; however, the potential lessens with extensive passaging. We investigated TGFβ-independent mechanisms that regulate RPE differentiation following repetitive passaging...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28106113/genetic-risk-variants-for-metabolic-traits-in-arab-populations
#12
Prashantha Hebbar, Naser Elkum, Fadi Alkayal, Sumi Elsa John, Thangavel Alphonse Thanaraj, Osama Alsmadi
Despite a high prevalence of metabolic trait related diseases in Arabian Peninsula, there is a lack of convincingly identified genetic determinants for metabolic traits in this population. Arab populations are underrepresented in global genome-wide association studies. We genotyped 1965 unrelated Arab individuals from Kuwait using Cardio-MetaboChip, and tested SNP associations with 13 metabolic traits. Models based on recessive mode of inheritance identified Chr15:40531386-rs12440118/ZNF106/W->R as a risk variant associated with glycated-hemoglobin at close to 'genome-wide significant' p-value and five other risk variants 'nominally' associated (p-value ≤ 5...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28025236/otx2-defines-a-subgroup-of-atypical-teratoid-rhabdoid-tumors-with-close-relationship-to-choroid-plexus-tumors
#13
Anna Sophia Japp, Ludger Klein-Hitpass, Dorota Denkhaus, Torsten Pietsch
Atypical teratoid rhabdoid tumors (ATRT) are highly malignant brain tumors of early childhood that have been regarded as a homogenous entity characterized by inactivation of the SMARCB1/INI1 or SMARCA4/BRG1 genes as the only characteristic alteration. Recent studies suggest that similar to other embryonal tumors ATRT can also be divided into subgroups based on their mRNA or methylation profiles. Using microarray-based expression analysis of 12 patient ATRT specimens we demonstrated the existence of 2 subgroups of ATRT...
December 26, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28008996/the-presence-of-anf-hesx1-homeobox-gene-in-lampreys-suggests-that-it-could-play-an-important-role-in-emergence-of-telencephalon
#14
Andrey V Bayramov, Galina V Ermakova, Fedor M Eroshkin, Alexandr V Kucheryavyy, Natalia Y Martynova, Andrey G Zaraisky
Accumulated evidence indicates that the core genetic mechanisms regulating early patterning of the brain rudiment in vertebrates are very similar to those operating during development of the anterior region of invertebrate embryos. However, the mechanisms underlying the morphological differences between the elaborate vertebrate brain and its simpler invertebrate counterpart remain poorly understood. Recently, we hypothesized that the emergence of the most anterior unit of the vertebrate brain, the telencephalon, could be related to the appearance in vertebrates' ancestors of a unique homeobox gene, Anf/Hesx1(further Anf), which is absent from all invertebrates and regulates the earliest steps of telencephalon development in vertebrates...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27974186/classical-and-non-classical-causes-of-gh-deficiency-in-the-paediatric-age
#15
REVIEW
Natascia Di Iorgi, Giovanni Morana, Anna Elsa Maria Allegri, Flavia Napoli, Roberto Gastaldi, Annalisa Calcagno, Giuseppa Patti, Sandro Loche, Mohamad Maghnie
Growth hormone deficiency (GHD) may result from a failure of hypothalamic GHRH production or release, from congenital disorders of pituitary development, or from central nervous system insults including tumors, surgery, trauma, radiation or infiltration from inflammatory diseases. Idiopathic, isolated GHD is the most common sporadic form of hypopituitarism. GHD may also occur in combination with other pituitary hormone deficiencies, and is often referred to as hypopituitarism, combined pituitary hormone deficiency (CPHD), multiple pituitary hormone deficiency (MPHD) or panhypopituitarism...
December 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/27965090/overexpression-of-mir-183-96-182-triggers-neuronal-cell-fate-in-human-retinal-pigment-epithelial-hrpe-cells-in-culture
#16
Maliheh Davari, Zahra-Soheila Soheili, Shahram Samiei, Zohreh Sharifi, Ehsan Ranaei Pirmardan
miR-183 cluster, composed of miR-183/-96/-182 genes, is highly expressed in the adult retina, particularly in photoreceptors. It involves in development, maturation and normal function of neuroretina. Ectopic overexpression of miR-183/-96/-182 genes was performed to assess reprogramming of hRPE cells. They were amplified from genomic DNA and cloned independently or in tandem configuration into pAAV.MCS vector. hRPE cells were then transfected with the recombinant constructs. Real-Time PCR was performed to measure the expression levels of miR-183/-96/-182 and that of several retina-specific neuronal genes such as OTX2, NRL, PDC and DCT...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27929058/tectal-derived-interneurons-contribute-to-phasic-and-tonic-inhibition-in-the-visual-thalamus
#17
Polona Jager, Zhiwen Ye, Xiao Yu, Laskaro Zagoraiou, Hong-Ting Prekop, Juha Partanen, Thomas M Jessell, William Wisden, Stephen G Brickley, Alessio Delogu
The release of GABA from local interneurons in the dorsal lateral geniculate nucleus (dLGN-INs) provides inhibitory control during visual processing within the thalamus. It is commonly assumed that this important class of interneurons originates from within the thalamic complex, but we now show that during early postnatal development Sox14/Otx2-expressing precursor cells migrate from the dorsal midbrain to generate dLGN-INs. The unexpected extra-diencephalic origin of dLGN-INs sets them apart from GABAergic neurons of the reticular thalamic nucleus...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27924227/otx2-impedes-self-renewal-of-porcine-ips-cells-through-downregulation-of-nanog-expression
#18
Ning Wang, Yaxian Wang, Youlong Xie, Huayan Wang
The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells. However, the molecular features and function of porcine OTX2 have not been well elucidated in porcine-induced pluripotent stem cells (piPSCs). By studying high-throughput transcriptome sequencing and interfering endogenous OTX2 expression, we demonstrate that OTX2 is able to downgrade the self-renewal of piPSCs. OTX2 is highly expressed in porcine brain, reproductive tissues, and preimplantation embryos, but is undetectable in fibroblasts and most somatic tissues...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27920151/lin28-is-induced-in-primed-embryonic-stem-cells-and-regulates-let-7-independent-events
#19
Silvia Parisi, Fabiana Passaro, Luigi Russo, Anna Musto, Angelica Navarra, Simona Romano, Giuseppe Petrosino, Tommaso Russo
Lin28 RNA-binding proteins play important roles in pluripotent stem cells, but the regulation of their expression and the mechanisms underlying their functions are still not definitively understood. Here we address the above-mentioned issues in the first steps of mouse embryonic stem cell (ESC) differentiation. We observed that the expression of Lin28 genes is transiently induced soon after the exit of ESCs from the naive ground state and that this induction is due to the Hmga2-dependent engagement of Otx2 with enhancers present at both Lin28 gene loci...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27917547/pituitary-stalk-interruption-syndrome-from-clinical-findings-to-pathogenesis
#20
REVIEW
C-Z Wang, L-L Guo, B-Y Han, X Su, Q-H Guo, Y-M Mu
Pituitary stalk interruption syndrome (PSIS) is a rare congenital defect manifesting with varying degrees of pituitary hormone deficiency. The signs and symptoms of PSIS during the neonatal period and infancy are often overlooked and therefore diagnosis is delayed. The typical manifestations of PSIS can be detected by magnetic resonance imaging. Several genes in the Wnt, Notch and Shh signalling pathways related to hypothalamic-pituitary development, such as PIT1, PROP1, LHX3/LHX4, PROKR2, OTX2, TGIF and HESX1, have been found to be associated with PSIS...
January 2017: Journal of Neuroendocrinology
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