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https://www.readbyqxmd.com/read/28899000/rhoa-rock-signalling-is-necessary-for-lateralization-and-differentiation-of-the-developing-sinoatrial-node
#1
Rebecca Vicente-Steijn, Tim P Kelder, Leon G Tertoolen, Lambertus J Wisse, Daniël A Pijnappels, Robert E Poelmann, Martin J Schalij, Marco C deRuiter, Adriana C Gittenberger-de Groot, Monique R M Jongbloed
Aims: RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential. Later, pacemaker potential is restricted to the right-sided SAN. Disruption of RHOA expression in adult mice causes arrhythmias including bradycardia and atrial fibrillation, the mechanism of which is unknown but presumed to affect the SAN...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28892058/glia-specific-enhancers-and-chromatin-structure-regulate-nfia-expression-and-glioma-tumorigenesis
#2
Stacey M Glasgow, Jeffrey C Carlson, Wenyi Zhu, Lesley S Chaboub, Peng Kang, Hyun Kyoung Lee, Yoanne M Clovis, Brittney E Lozzi, Robert J McEvilly, Michael G Rosenfeld, Chad J Creighton, Soo-Kyung Lee, Carrie A Mohila, Benjamin Deneen
Long-range enhancer interactions critically regulate gene expression, yet little is known about how their coordinated activities contribute to CNS development or how this may, in turn, relate to disease states. By examining the regulation of the transcription factor NFIA in the developing spinal cord, we identified long-range enhancers that recapitulate NFIA expression across glial and neuronal lineages in vivo. Complementary genetic studies found that Sox9-Brn2 and Isl1-Lhx3 regulate enhancer activity and NFIA expression in glial and neuronal populations...
September 11, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28886366/micrornas-induce-a-permissive-chromatin-environment-that-enables-neuronal-subtype-specific-reprogramming-of-adult-human-fibroblasts
#3
Daniel G Abernathy, Woo Kyung Kim, Matthew J McCoy, Allison M Lake, Rebecca Ouwenga, Seong Won Lee, Xiaoyun Xing, Daofeng Li, Hyung Joo Lee, Robert O Heuckeroth, Joseph D Dougherty, Ting Wang, Andrew S Yoo
Directed reprogramming of human fibroblasts into fully differentiated neurons requires massive changes in epigenetic and transcriptional states. Induction of a chromatin environment permissive for acquiring neuronal subtype identity is therefore a major barrier to fate conversion. Here we show that the brain-enriched miRNAs miR-9/9(∗) and miR-124 (miR-9/9(∗)-124) trigger reconfiguration of chromatin accessibility, DNA methylation, and mRNA expression to induce a default neuronal state. miR-9/9(∗)-124-induced neurons (miNs) are functionally excitable and uncommitted toward specific subtypes but possess open chromatin at neuronal subtype-specific loci, suggesting that such identity can be imparted by additional lineage-specific transcription factors...
September 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28864896/dependence-of-expression-of-regulatory-master-genes-of-embryonic-development-in-pancreatic-cancer-cells-on-the-intracellular-concentration-of-the-master-regulator-pdx1
#4
L G Kondratyeva, D A Didych, I P Chernov, E P Kopantzev, E A Stukacheva, T V Vinogradova, E D Sverdlov
Exogenous expression of the gene encoding the pancreatic master regulator PDX1 in cell lines with different degrees of differentiation of pancreatic cancer cells is accompanied by changes in the expression of known master genes involved in cancer progression. In BxPC3(PDX+) cells, as compared to BxPC3(PDX-), we detected an increased expression of the following genes: NKX6.1 (2 times), NR5A2 (2.5 times), KLF5 (1.8 times), ZEB1 (3 times), and ONECUT1 (1.3 times), as well as a decreased expression of MUC1 and SLUG genes (3 and 2 times, respectively)...
July 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28796037/functional-prediction-of-mir-3144-5p-in-human-cardiac-myocytes-based-on-transcriptome-sequencing-and-bioinformatics
#5
Lei Ruan, Yi Yang, Yi Huang, Ling Ding, Cuntai Zhang, Xiaofen Wu
BACKGROUND: RAN guanine nucleotide release factor (RANGRF) encoding protein MOG1 plays an important role in cardiac arrhythmia, so we intended to investigate the regulatory miRNA of RANGRF and explore its potential regulatory mechanism in arrhythmogenesis. METHODS: Based on bioinformatic analysis, miR-3144-5p was predicted to be a regulatory miRNA of RANGRF, which were then validated through a dual-luciferase reporter plasmid assay. Subsequently, the expression level of miR-3144-5p in human cardiac myocytes (HCMs) was detected, followed by cell transfection with miR-3144-5p mimics...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28794909/role-of-the-lf-sine-derived-distal-isl1-enhancer-in-patients-with-classic-bladder-exstrophy
#6
Rong Zhang, Michael Knapp, Franziska Kause, Heiko Reutter, Michael Ludwig
A genome-wide association study and meta-analysis identified ISL1 as the first genome-wide significant susceptibility gene for classic bladder exstrophy (CBE). A short interspersed repetitive element (SINE), first detected in lobe-finned fishes (LF-SINE), was shown to drive Isl1 expression in embryonic mouse genital eminence. Hence, we assumed this enhancer a conclusive target for mutations associated with CBE formation and analyzed a cohort of 200 CBE patients. Although we identified two enhancer variants in five CBE patients, their clinical significance seems unlikely, implying that sequence variants in the ISL1 LF-SINE enhancer are not frequently associated with CBE...
September 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/28751678/morpho-functional-characterization-of-the-systemic-venous-pole-of-the-reptile-heart
#7
Bjarke Jensen, Signe Vesterskov, Bastiaan J Boukens, Jan M Nielsen, Antoon F M Moorman, Vincent M Christoffels, Tobias Wang
Mammals evolved from reptile-like ancestors, and while the mammalian heart is driven by a distinct sinus node, a sinus node is not apparent in reptiles. We characterized the myocardial systemic venous pole, the sinus venosus, in reptiles to identify the dominant pacemaker and to assess whether the sinus venosus remodels and adopts an atrium-like phenotype as observed in mammals. Anolis lizards had an extensive sinus venosus of myocardium expressing Tbx18. A small sub-population of cells encircling the sinuatrial junction expressed Isl1, Bmp2, Tbx3, and Hcn4, homologues of genes marking the mammalian sinus node...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28676648/interactions-between-lhx3-and-isl1-family-lim-homeodomain-transcription-factors-are-conserved-in-caenorhabditis-elegans
#8
Mugdha Bhati, Estelle Llamosas, David A Jacques, Cy M Jeffries, Siavoush Dastmalchi, Nina Ripin, Hannah R Nicholas, Jacqueline M Matthews
LIM-Homeodomain (LIM-HD) transcription factors are highly conserved in animals where they are thought to act in a transcriptional 'LIM code' that specifies cell types, particularly in the central nervous system. In chick and mammals the interaction between two LIM-HD proteins, LHX3 and Islet1 (ISL1), is essential for the development of motor neurons. Using yeast two-hybrid analysis we showed that the Caenorhabditis elegans orthologs of LHX3 and ISL1, CEH-14 and LIM-7 can physically interact. Structural characterisation of a complex comprising the LIM domains from CEH-14 and a LIM-interaction domain from LIM-7 showed that these nematode proteins assemble to form a structure that closely resembles that of their vertebrate counterparts...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28671548/motoneurons-regulate-the-central-pattern-generator-during-drug-induced-locomotor-like-activity-in-the-neonatal-mouse
#9
Melanie Falgairolle, Joshua G Puhl, Avinash Pujala, Wenfang Liu, Michael J O'Donovan
Motoneurons are traditionally viewed as the output of the spinal cord that do not influence locomotor rhythmogenesis. We assessed the role of motoneuron firing during ongoing locomotor-like activity in neonatal mice expressing archaerhopsin-3 (Arch), halorhodopsin (eNpHR), or channelrhodopsin-2 (ChR2) in Choline acetyltransferase neurons (ChAT(+)) or Arch in LIM-homeodomain transcription factor Isl1(+) neurons. Illumination of the lumbar cord in mice expressing eNpHR or Arch in ChAT(+) or Isl1(+) neurons, depressed motoneuron discharge, transiently decreased the frequency, and perturbed the phasing of the locomotor-like rhythm...
July 3, 2017: ELife
https://www.readbyqxmd.com/read/28650075/isl1-controls-patterning-and-mineralization-of-enamel-in-the-continuously-renewing-mouse-incisor
#10
Adrien Naveau, Bin Zhang, Bo Meng, McGarrett T Sutherland, Michaela Prochazkova, Timothy Wen, Pauline Marangoni, Kyle B Jones, Timothy C Cox, Bernhard Ganss, Andrew H Jheon, Ophir D Klein
Rodents are characterized by continuously renewing incisors whose growth is fueled by epithelial and mesenchymal stem cells housed in the proximal compartments of the tooth. The epithelial stem cells reside in structures known as the labial (toward the lip) and lingual (toward the tongue) cervical loops (laCL and liCL, respectively). An important feature of the rodent incisor is that enamel, the outer, highly mineralized layer, is asymmetrically distributed, because it is normally generated by the laCL but not the liCL...
June 26, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28648899/transient-hes5-activity-instructs-mesodermal-cells-toward-a-cardiac-fate
#11
Ana G Freire, Avinash Waghray, Francisca Soares-da-Silva, Tatiana P Resende, Dung-Fang Lee, Carlos-Filipe Pereira, Diana S Nascimento, Ihor R Lemischka, Perpétua Pinto-do-Ó
Notch signaling plays a role in specifying a cardiac fate but the downstream effectors remain unknown. In this study we implicate the Notch downstream effector HES5 in cardiogenesis. We show transient Hes5 expression in early mesoderm of gastrulating embryos and demonstrate, by loss and gain-of-function experiments in mouse embryonic stem cells, that HES5 favors cardiac over primitive erythroid fate. Hes5 overexpression promotes upregulation of the cardiac gene Isl1, while the hematopoietic regulator Scl is downregulated...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28647274/sonic-hedgehog-pathway-suppression-and-reactivation-accelerates-differentiation-of-rat-adipose-derived-mesenchymal-stromal-cells-toward-insulin-producing-cells
#12
Dian Dayer, Mahmoud Hashemi Tabar, Eskandar Moghimipour, Mohammad Reza Tabandeh, Ata A Ghadiri, Elham Allah Bakhshi, Mahmoud Orazizadeh, Mohammad Ali Ghafari
BACKGROUND AIMS: Sonic hedgehog (Shh) is an intercellular signaling molecule that regulates pancreas development in mammals. Manipulation of Shh signaling pathway can be used as reliable approach to improve the generation of functional insulin-producing cells (IPCs) from mesenchymal stromal cells (MSCs). METHODS: In the present study, a novel differentiation protocol was used to produce IPCs from adipose tissue-derived MSCs (ATDMSCs) based on sequential inhibition and reactivation of Shh pathway...
June 21, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28624850/the-plant-lim-proteins-unlocking-the-hidden-attractions
#13
REVIEW
Vikas Srivastava, Praveen Kumar Verma
The plant LIMs comprise two sub-families with one (DA1/DAR) and two (2LIM) LIM domains. This review comprehensively discussed the structure and potential role of this protein family in diverse area of plant biology. The description of first eukaryote lineage-specific plant LIM domain (LIN11, ISL1, and MEC3) proteins was observed in Helianthus long back. The successive study of LIM proteins in diverse plants has shown its vital relation to development, metabolism and defence. This nascent gene family has been worked out for their role in actin dynamics, organ size determination and transcription regulation...
June 17, 2017: Planta
https://www.readbyqxmd.com/read/28586118/a-dna-hypermethylation-profile-reveals-new-potential-biomarkers-for-the-evaluation-of-prognosis-in-urothelial-bladder-cancer
#14
Jose I López, Javier C Angulo, Ana Martín, Manuel Sánchez-Chapado, Ana González-Corpas, Begoña Colás, Santiago Ropero
DNA hypermethylation has emerged as a molecular biomarker for the evaluation of cancer diagnosis and prognosis. We define a methylation signature of bladder cancer and evaluate whether this profile assesses prognosis of patients. Genome-wide methylation analysis was performed on 70 tumor and 10 normal bladder samples. Hypermethylation status of 1505 CpGs present in the promoter region of 807 genes was studied. Thirty-three genes were significantly hypermethylated in ≥10% of the tumors. Three clusters of patients were characterized by their DNA methylation profile, one at higher risk of dead of disease (p = 0...
September 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28498280/immunohistochemical-characterization-of-the-origins-of-metastatic-well-differentiated-neuroendocrine-tumors-to-the-liver
#15
Zhaohai Yang, David S Klimstra, Ralph H Hruban, Laura H Tang
Metastatic neoplasms of unknown primary site pose a major challenge to patient management. As targeted therapies are now being tailored to neuroendocrine tumors (NETs) of different primary sites, identifying the origin of metastatic NETs has become increasingly important. Compared with more extensive efforts on metastatic adenocarcinomas of unknown primary, the literature on metastatic NETs (often to the liver) is relatively sparse and most studies are based on primary tumors. We sought to study metastatic well-differentiated NETs to the liver to identify markers that predict the site of origin...
July 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28472858/selective-neuronal-expression-of-the-soxe-factor-sox8-in-direct-pathway-striatal-projection-neurons-of-the-developing-mouse-brain
#16
Paloma Merchan-Sala, Diana Nardini, Ronald R Waclaw, Kenneth Campbell
The striatum is the major component of the basal ganglia and is well known to play a key role in the control of motor function via balanced output from the indirect (iSPNs) and direct pathway striatal projection neurons (dSPNs). Little is known, however, about the molecular genetic mechanisms that control the formation of the iSPNs versus dSPNs. We show here that the SoxE family member, Sox8, is co-expressed with the dSPN markers, Isl1 and Ebf1, in the developing striatum. Moreover, dSPNs, as marked by Isl1-cre fate map, express Sox8 in the embryonic striatum and Sox8-EGFP BAC transgenic mice specifically reveal the direct pathway axons during development...
September 1, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28451636/the-isl1-lhx3-complex-promotes-motor-neuron-specification-by-activating-transcriptional-pathways-that-enhance-its-own-expression-and-formation
#17
Madalynn Erb, Bora Lee, So Yeon Seo, Jae W Lee, Seunghee Lee, Soo-Kyung Lee
Motor neuron (MN) progenitor cells rapidly induce high expression of the transcription factors Islet-1 (Isl1), LIM-homeobox 3 (Lhx3), and the transcriptional regulator LMO4, as they differentiate. While these factors are critical for MN specification, the mechanisms regulating their precise temporal and spatial expression patterns are not well characterized. Isl1 and Lhx3 form the Isl1-Lhx3 complex, which induces the transcription of genes critical for MN specification and maturation. Here, we report that Isl1, Lhx3, and Lmo4 are direct target genes of the Isl1-Lhx3 complex...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28436940/disruption-of-spatiotemporal-hypoxic-signaling-causes-congenital-heart-disease-in-mice
#18
Xuejun Yuan, Hui Qi, Xiang Li, Fan Wu, Jian Fang, Eva Bober, Gergana Dobreva, Yonggang Zhou, Thomas Braun
Congenital heart disease (CHD) represents the most prevalent inborn anomaly. Only a minority of CHD cases are attributed to genetic causes, suggesting a major role of environmental factors. Nonphysiological hypoxia during early pregnancy induces CHD, but the underlying reasons are unknown. Here, we have demonstrated that cells in the mouse heart tube are hypoxic, while cardiac progenitor cells (CPCs) expressing islet 1 (ISL1) in the secondary heart field (SHF) are normoxic. In ISL1+ CPCs, induction of hypoxic responses caused CHD by repressing Isl1 and activating NK2 homeobox 5 (Nkx2...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28386378/transplantation-of-multipotent-isl1-cardiac-progenitor-cells-preserves-infarcted-heart-function-in-mice
#19
Yunpeng Li, Shuo Tian, Ienglam Lei, Liu Liu, Peter Ma, Zhong Wang
Cell-based cardiac therapy is a promising therapeutic strategy to restore heart function after myocardial infarction (MI). However, the cell type selection and ensuing effects remain controversial. Here, we intramyocardially injected Isl1+ cardiac progenitor cells (CPCs) derived from EGFP/luciferase double-tagged mouse embryonic stem (dt-mES) cells with vehicle (fibrin gel) or phosphate-buffered saline (PBS) into the infarcted area in nude mice to assess the contribution of CPCs to the recovery of cardiac function post-MI...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28257739/candidate-gene-analyses-of-3-dimensional-dentoalveolar-phenotypes-in-subjects-with-malocclusion
#20
Cole A Weaver, Steven F Miller, Clarissa S G da Fontoura, George L Wehby, Brad A Amendt, Nathan E Holton, Veeratrishul Allareddy, Thomas E Southard, Lina M Moreno Uribe
INTRODUCTION: Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes DUSP6,ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion...
March 2017: American Journal of Orthodontics and Dentofacial Orthopedics
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