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https://www.readbyqxmd.com/read/29180489/downregulation-of-nfat3-due-to-lack-of-t-box-transcription-factor-tbx5-is-crucial-for-cytokine-expression-in-t-cells
#1
Osamu Kaminuma, Noriko Kitamura, Yasumasa Nishito, Soichi Nemoto, Hideki Tatsumi, Akio Mori, Takachika Hiroi
The NFAT family transcription factors play crucial roles in immunological and other biological activities. NFAT3 is rarely expressed in T cells, and the mechanisms and significance of the specific NFAT3 downregulation in T cells have been unknown. In human CD4+ T cells, overexpression of NFAT1 and NFAT3 enhanced and suppressed IL-2 expression, respectively. NFAT3 downregulation in Jurkat cells using RNA interference technology augmented IL-2 expression, whereas a knockdown of NFAT1, NFAT2, and NFAT4 suppressed it...
November 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29174768/acetylation-of-tbx5-by-kat2b-and-kat2a-regulates-heart-and-limb-development
#2
Tushar K Ghosh, José J Aparicio-Sánchez, Sarah Buxton, Ami Ketley, Tasabeeh Mohamed, Catrin S Rutland, Siobhan Loughna, J David Brook
TBX5 plays a critical role in heart and forelimb development. Mutations in TBX5 cause Holt-Oram syndrome, an autosomal dominant condition that affects the formation of the heart and upper-limb. Several studies have provided significant insight into the role of TBX5 in cardiogenesis; however, how TBX5 activity is regulated by other factors is still unknown. Here we report that histone acetyltransferases KAT2A and KAT2B associate with TBX5 and acetylate it at Lys339. Acetylation potentiates its transcriptional activity and is required for nuclear retention...
November 22, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29169318/genome-wide-dna-methylation-profiling-reveals-novel-epigenetic-signatures-in-squamous-cell-lung-cancer
#3
Yuan-Xiang Shi, Ying Wang, Xi Li, Wei Zhang, Hong-Hao Zhou, Ji-Ye Yin, Zhao-Qian Liu
BACKGROUND: Epigenetic alterations are strongly associated with the development of cancer. The aim of this study was to identify epigenetic pattern in squamous cell lung cancer (LUSC) on a genome-wide scale. RESULTS: Here we performed DNA methylation profiling on 24 LUSC and paired non-tumor lung (NTL) tissues by Illumina Human Methylation 450 K BeadArrays, and identified 5214 differentially methylated probes. By integrating DNA methylation and mRNA expression data, 449 aberrantly methylated genes accompanied with altered expression were identified...
November 23, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29156374/genetic-profiling-and-surface-proteome-analysis-of-human-atrial-stromal-cells-and-rat-ventricular-epicardium-derived-cells-reveals-novel-insights-into-their-cardiogenic-potential
#4
Sebastian Temme, Daniela Friebe, Timo Schmidt, Gereon Poschmann, Julia Hesse, Bodo Steckel, Kai Stühler, Meik Kunz, Thomas Dandekar, Zhaoping Ding, Payam Akhyari, Artur Lichtenberg, Jürgen Schrader
Epicardium-derived cells (EPDC) and atrial stromal cells (ASC) display cardio-regenerative potential, but the molecular details are still unexplored. Signals which induce activation, migration and differentiation of these cells are largely unknown. Here we have isolated rat ventricular EPDC and rat/human ASC and performed genetic and proteomic profiling. EPDC and ASC expressed epicardial/mesenchymal markers (WT-1, Tbx18, CD73, CD90, CD44, CD105), cardiac markers (Gata4, Tbx5, troponin T) and also contained phosphocreatine...
November 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29100088/natural-selection-on-genes-related-to-cardiovascular-health-in-high-altitude-adapted-andeans
#5
Jacob E Crawford, Ricardo Amaru, Jihyun Song, Colleen G Julian, Fernando Racimo, Jade Yu Cheng, Xiuqing Guo, Jie Yao, Bharath Ambale-Venkatesh, João A Lima, Jerome I Rotter, Josef Stehlik, Lorna G Moore, Josef T Prchal, Rasmus Nielsen
The increase in red blood cell mass (polycythemia) due to the reduced oxygen availability (hypoxia) of residence at high altitude or other conditions is generally thought to be beneficial in terms of increasing tissue oxygen supply. However, the extreme polycythemia and accompanying increased mortality due to heart failure in chronic mountain sickness most likely reduces fitness. Tibetan highlanders have adapted to high altitude, possibly in part via the selection of genetic variants associated with reduced polycythemic response to hypoxia...
November 2, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29066419/effect-of-stem-cell-niche-elasticity-ecm-protein-on-the-self-beating-cardiomyocyte-differentiation-of-inducedpluripotent-stem-ips-cells-at-different-stages
#6
Mitsuhi Hirata, Tetsuji Yamaoka
Stem cell-based myocardial regeneration therapies have emerged as alternative strategies to heart transplantation for serious heart diseases, but autologous beating mature cardiomyocytes are not available. Here we investigated the effect of culture substrates on the cardiomyocyte differentiation of induced pluripotent stem cells (iPSs) in vitro by separately evaluating the following continuous three steps: (1) cardiac marker gene expression, (2) contractile gene expression and self-beating, and (3) beating duration...
October 21, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29045289/genetic-origins-of-tetralogy-of-fallot
#7
Ari Morgenthau, William H Frishman
Due to improved survival and clinical outcomes, congenital heart disease is an area of growing importance within the medical community. As these patients reach adulthood and have children, there has been a growing appreciation for the increased risk of CHD among their offspring, strongly implying a genetic element. Given the growing wealth of genetic data available and these clinical implications, this review serves to re-examine the role of genetics within CHD, using Tetralogy of Fallot as a model pathology...
October 17, 2017: Cardiology in Review
https://www.readbyqxmd.com/read/29037217/subtype-specific-differentiation-of-cardiac-pacemaker-cell-clusters-from-human-induced-pluripotent-stem-cells
#8
Patrick A Schweizer, Fabrice F Darche, Nina D Ullrich, Pascal Geschwill, Boris Greber, Rasmus Rivinius, Claudia Seyler, Karin Müller-Decker, Andreas Draguhn, Jochen Utikal, Michael Koenen, Hugo A Katus, Dierk Thomas
BACKGROUND: Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties. METHODS: hiPSC were differentiated into spontaneously beating clusters by co-culturing with visceral endoderm-like cells in a serum-free medium...
October 16, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28982760/znf281-enhances-cardiac-reprogramming-by-modulating-cardiac-and-inflammatory-gene-expression
#9
Huanyu Zhou, Maria Gabriela Morales, Hisayuki Hashimoto, Matthew E Dickson, Kunhua Song, Wenduo Ye, Min S Kim, Hanspeter Niederstrasser, Zhaoning Wang, Beibei Chen, Bruce A Posner, Rhonda Bassel-Duby, Eric N Olson
Direct reprogramming of fibroblasts to cardiomyocytes represents a potential means of restoring cardiac function following myocardial injury. AKT1 in the presence of four cardiogenic transcription factors, GATA4, HAND2, MEF2C, and TBX5 (AGHMT), efficiently induces the cardiac gene program in mouse embryonic fibroblasts but not adult fibroblasts. To identify additional regulators of adult cardiac reprogramming, we performed an unbiased screen of transcription factors and cytokines for those that might enhance or suppress the cardiogenic activity of AGHMT in adult mouse fibroblasts...
September 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28971975/tbx4-is-involved-in-the-super-enhancer-driven-transcriptional-programs-underlying-features-specific-to-lung-fibroblasts
#10
Masafumi Horie, Naoya Miyashita, Yu Mikami, Satoshi Noguchi, Yasuhiro Yamauchi, Maho Suzukawa, Takeshi Fukami, Ken Ohta, Yoshihide Asano, Shinichi Sato, Yoko Yamaguchi, Mitsuhiro Ohshima, Hiroshi I Suzuki, Akira Saito, Takahide Nagase
Lung fibroblasts participate in the pathogenesis of respiratory diseases, including lung cancer and pulmonary fibrosis. Although fibroblasts are ubiquitous constituents of various organs, their cellular diversity among different organs has been poorly characterized. Here, we aimed to investigate the distinct gene signature of lung fibroblasts that represents its pulmonary origin, and the underlying gene regulatory networks. Promoter-level differential expression analysis by cap analysis of gene expression (CAGE) sequencing revealed distinct gene expression patterns of fibroblasts derived from different anatomical sites and identified 88 coding genes with higher expression in lung fibroblasts relative to other fibroblasts...
September 28, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28961683/contiguous-gene-deletion-of-tbx5-and-tbx3-report-of-another-case
#11
Francesca Forzano, Patricia A Foley, Morgan R Keane, Caroline E Brain, Gill D Smith, Robert W Yates, Drew Ellershaw, Alistair D Calder, Richard H Scott
No abstract text is available yet for this article.
September 28, 2017: Clinical Dysmorphology
https://www.readbyqxmd.com/read/28899000/rhoa-rock-signalling-is-necessary-for-lateralization-and-differentiation-of-the-developing-sinoatrial-node
#12
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/28834610/nestin-expression-is-dynamically-regulated-in-cardiomyocytes-during-embryogenesis
#13
Vanessa Hertig, Adrianna Matos Nieves, Vidu Garg, Louis Villeneuve, Maya Mamarbachi, Laurie Caland, Angelino Calderone
The transcriptional factors implicated in the expression of the intermediate filament protein nestin in cardiomyocytes during embryogenesis remain undefined. In the heart of 9,5-10,5 day embryonic mice, nestin staining was detected in atrial and ventricular cardiomyocytes and a subpopulation co-expressed Tbx5. At later stages of development, nestin immunoreactivity in cardiomyocytes gradually diminished and was absent in the heart of 17,5 day embryonic mice. In the heart of wild type 11,5 day embryonic mice, 54 ± 7% of the trabeculae expressed nestin and the percentage was significantly increased in the hearts of Tbx5(+/-) and Gata4(+/-) embryos...
August 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28825623/single-construct-polycistronic-doxycycline-inducible-vectors-improve-direct-cardiac-reprogramming-and-can-be-used-to-identify-the-critical-timing-of-transgene-expression
#14
Tomohiko C Umei, Hiroyuki Yamakawa, Naoto Muraoka, Taketaro Sadahiro, Mari Isomi, Sho Haginiwa, Hidenori Kojima, Shota Kurotsu, Fumiya Tamura, Rina Osakabe, Hidenori Tani, Kaori Nara, Hiroyuki Miyoshi, Keiichi Fukuda, Masaki Ieda
Direct reprogramming is a promising approach in regenerative medicine. Overexpression of the cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2 (GHMT) directly reprogram fibroblasts into cardiomyocyte-like cells (iCMs). However, the critical timing of transgene expression and the molecular mechanisms for cardiac reprogramming remain unclear. The conventional doxycycline (Dox)-inducible temporal transgene expression systems require simultaneous transduction of two vectors (pLVX-rtTA/pLVX-cDNA) harboring the reverse tetracycline transactivator (rtTA) and the tetracycline response element (TRE)-controlled transgene, respectively, leading to inefficient cardiac reprogramming...
August 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28807900/heart-morphogenesis-gene-regulatory-networks-revealed-by-temporal-expression-analysis
#15
Jonathon T Hill, Bradley Demarest, Bushra Gorsi, Megan Smith, H Joseph Yost
During embryogenesis the heart forms as a linear tube that then undergoes multiple simultaneous morphogenetic events to obtain its mature shape. To understand the gene regulatory networks (GRNs) driving this phase of heart development, during which many congenital heart disease malformations likely arise, we conducted an RNA-seq timecourse in zebrafish from 30 hpf to 72 hpf and identified 5861 genes with altered expression. We clustered the genes by temporal expression pattern, identified transcription factor binding motifs enriched in each cluster, and generated a model GRN for the major gene batteries in heart morphogenesis...
October 1, 2017: Development
https://www.readbyqxmd.com/read/28794112/fifteen-genetic-loci-associated-with-the-electrocardiographic-p-wave
#16
Ingrid E Christophersen, Jared W Magnani, Xiaoyan Yin, John Barnard, Lu-Chen Weng, Dan E Arking, Maartje N Niemeijer, Steven A Lubitz, Christy L Avery, Qing Duan, Stephan B Felix, Joshua C Bis, Kathleen F Kerr, Aaron Isaacs, Martina Müller-Nurasyid, Christian Müller, Kari E North, Alex P Reiner, Lesley F Tinker, Jan A Kors, Alexander Teumer, Astrid Petersmann, Moritz F Sinner, Petra Buzkova, Jonathan D Smith, David R Van Wagoner, Uwe Völker, Melanie Waldenberger, Annette Peters, Thomas Meitinger, Marian C Limacher, Kirk C Wilhelmsen, Bruce M Psaty, Albert Hofman, Andre Uitterlinden, Bouwe P Krijthe, Zhu-Ming Zhang, Renate B Schnabel, Stefan Kääb, Cornelia van Duijn, Jerome I Rotter, Nona Sotoodehnia, Marcus Dörr, Yun Li, Mina K Chung, Elsayed Z Soliman, Alvaro Alonso, Eric A Whitsel, Bruno H Stricker, Emelia J Benjamin, Susan R Heckbert, Patrick T Ellinor
BACKGROUND: The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies...
August 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28782180/down-regulation-of-mir-10a-5p-in-synoviocytes-contributes-to-tbx5-controlled-joint-inflammation
#17
Nazim Hussain, Wenhua Zhu, Congshan Jiang, Jing Xu, Xiaoying Wu, Manman Geng, Safdar Hussain, Yongsong Cai, Ke Xu, Peng Xu, Yan Han, Jian Sun, Liesu Meng, Shemin Lu
MicroRNAs are considered to play critical roles in the pathogenesis of human inflammatory arthritis, including rheumatoid arthritis (RA). The purpose of this study was to determine the relationship between miR-10a-5p and TBX5 in synoviocytes and evaluate their contribution to joint inflammation. The expression of miR-10a-5p and TBX5 in the synovium of RA and human synovial sarcoma cell line SW982 stimulated by IL-1β was determined by RT-qPCR and Western blotting. The direct interaction between miR-10a-5p and TBX5 3'UTR was determined by dual-luciferase reporter assay in HeLa cells...
August 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28761722/a-tbx5-3-utr-variant-increases-the-risk-of-congenital-heart-disease-in-the-han-chinese-population
#18
Feng Wang, Dong Liu, Ran-Ran Zhang, Li-Wei Yu, Jian-Yuan Zhao, Xue-Yan Yang, Song-Shan Jiang, Duan Ma, Bin Qiao, Feng Zhang, Li Jin, Yong-Hao Gui, Hong-Yan Wang
TBX5 is a vital transcription factor involved in cardiac development in a dosage-dependent manner. But little is known about the potential association of TBX5 3' untranslated region (UTR) variations with congenital cardiac malformations. This study aimed to investigate the relationship between TBX5 3'UTR variants and risk for congenital heart disease (CHD) susceptibility in two Han Chinese populations, and to reveal its molecular mechanism. The relationship between TBX5 3'UTR variants and CHD susceptibility was examined in 1 177 CHD patients and 990 healthy controls in two independent case-control studies...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28711329/cardiac-reprogramming-factor-gata4-reduces-postinfarct-cardiac-fibrosis-through-direct-repression-of-the-profibrotic-mediator-snail
#19
Megumi Mathison, Vivek P Singh, Deepthi Sanagasetti, Lina Yang, Jaya Pratap Pinnamaneni, Jianchang Yang, Todd K Rosengart
OBJECTIVE: The administration of a variety of reprogramming factor cocktails has now been shown to reprogram cardiac fibroblasts into induced cardiomyocyte-like cells. However, reductions in ventricular fibrosis observed after reprogramming factor administration seem to far exceed the extent of induced cardiomyocyte-like cell generation in vivo. We investigated whether reprogramming factor administration might primarily play a role in activating antifibrotic molecular pathways. METHODS: Adult rat cardiac fibroblasts were infected with lentivirus encoding the transcription factors Gata4, Mef2c, or Tbx5, all 3 vectors, or a green fluorescent protein control vector...
November 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28674041/transient-notch-activation-induces-long-term-gene-expression-changes-leading-to-sick-sinus-syndrome-in-mice
#20
Yun Qiao, Catherine Lipovsky, Stephanie Hicks, Somya Bhatnagar, Gang Li, Aditi Khandekar, Robert Guzy, Kel Vin Woo, Colin G Nichols, Igor R Efimov, Stacey Rentschler
RATIONALE: Notch signaling programs cardiac conduction during development, and in the adult ventricle, injury-induced Notch reactivation initiates global transcriptional and epigenetic changes. OBJECTIVE: To determine whether Notch reactivation may stably alter atrial ion channel gene expression and arrhythmia inducibility. METHODS AND RESULTS: To model an injury response and determine the effects of Notch signaling on atrial electrophysiology, we transiently activate Notch signaling within adult myocardium using a doxycycline-inducible genetic system (inducible Notch intracellular domain [iNICD])...
August 18, 2017: Circulation Research
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