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https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#1
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...
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28194008/genetic-otx2-mis-localization-delays-critical-period-plasticity-across-brain-regions
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27909008/trajectory-of-parvalbumin-cell-impairment-and-loss-of-cortical-inhibition-in-traumatic-brain-injury
#15
Tsung-Hsun Hsieh, Henry Hing Cheong Lee, Mustafa Qadir Hameed, Alvaro Pascual-Leone, Takao K Hensch, Alexander Rotenberg
Many neuropsychiatric symptoms that follow traumatic brain injury (TBI), including mood disorders, sleep disturbance, chronic pain, and posttraumatic epilepsy (PTE) are attributable to compromised cortical inhibition. However, the temporal trajectory of cortical inhibition loss and its underlying mechanisms are not known. Using paired-pulse transcranial magnetic stimulation (ppTMS) and immunohistochemistry, we tracked functional and cellular changes of cortical inhibitory network elements after fluid-percussion injury (FPI) in rats...
November 30, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27812821/early-retinal-differentiation-of-human-pluripotent-stem-cells-in-microwell-suspension-cultures
#16
Vishal S Sharma, Rana Khalife, Rui Tostoes, Leonard Leung, Rose Kinsella, Ludmilla Ruban, Farlan S Veraitch
OBJECTIVE: To develop a microwell suspension platform for the adaption of attached stem cell differentiation protocols into mixed suspension culture. RESULTS: We adapted an adherent protocol for the retinal differentiation of human induced pluripotent stem cells (hiPSCs) using a two-step protocol. Establishing the optimum embryoid body (EB) starting size and shaking speed resulted in the translation of the original adherent process into suspension culture. Embryoid bodies expanded in size as the culture progressed resulting in the expression of characteristic markers of early (Rx, Six and Otx2) and late (Crx, Nrl and Rhodopsin) retinal differentiation...
February 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/27805868/ovariectomy-alters-gene-expression-of-the-hippocampal-formation-in-middle-aged-rats
#17
Miklós Sárvári, Imre Kalló, Erik Hrabovszky, Norbert Solymosi, Zsolt Liposits
Ovarian hormones regulate the transcriptome of the hippocampus and modulate its functions. During menopause this complex signaling declines, leading to impaired learning and memory. This study was undertaken to clarify the effects of long-term, surgical ovariectomy (OVX) on the rat hippocampal transcriptome. At age of 13 months, intact control and ovariectomized groups were formed. All animals were sacrificed 5 weeks after gonadectomy, hippocampal formations were dissected and processed for transcriptome analysis...
November 2, 2016: Endocrinology
https://www.readbyqxmd.com/read/27782156/identification-and-validation-of-candidate-epigenetic-biomarkers-in-lung-adenocarcinoma
#18
Iben Daugaard, Diana Dominguez, Tina E Kjeldsen, Lasse S Kristensen, Henrik Hager, Tomasz K Wojdacz, Lise Lotte Hansen
Lung cancer is the number one cause of cancer-related deaths worldwide. DNA methylation is an epigenetic mechanism that regulates gene expression, and disease-specific methylation changes can be targeted as biomarkers. We have compared the genome-wide methylation pattern in tumor and tumor-adjacent normal lung tissue from four lung adenocarcinoma (LAC) patients using DNA methylation microarrays and identified 74 differentially methylated regions (DMRs). Eighteen DMRs were selected for validation in a cohort comprising primary tumors from 52 LAC patients and tumor-adjacent normal lung tissue from 32 patients by methylation-sensitive high resolution melting (MS-HRM) analysis...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27781424/update-on-the-integrated-histopathological-and-genetic-classification-of-medulloblastoma-a-practical-diagnostic-guideline
#19
Torsten Pietsch, Christine Haberler
The revised WHO classification of tumors of the CNS 2016 has introduced the concept of the integrated diagnosis. The definition of medulloblastoma entities now requires a combination of the traditional histological information with additional molecular/genetic features. For definition of the histopathological component of the medulloblastoma diagnosis, the tumors should be assigned to one of the four entities classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma...
November 2016: Clinical Neuropathology
https://www.readbyqxmd.com/read/27742845/efficiently-specified-ventral-midbrain-dopamine-neurons-from-human-pluripotent-stem-cells-under-xeno-free-conditions-restore-motor-deficits-in-parkinsonian-rodents
#20
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...
October 14, 2016: Stem Cells Translational Medicine
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