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https://www.readbyqxmd.com/read/28807900/heart-morphogenesis-gene-regulatory-networks-revealed-by-temporal-expression-analysis
#1
Jonathon T Hill, Bradley Demarest, Megan Smith, Bushra Gorsi, 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 time course in zebrafish from 30 hpf to 72 hpf and identified 5,861 genes with altered expression. We then 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...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28794112/fifteen-genetic-loci-associated-with-the-electrocardiographic-p-wave
#2
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
#3
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
#4
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
#5
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...
June 21, 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
#6
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
https://www.readbyqxmd.com/read/28656050/mir-142-3p-contributes-to-early-cardiac-fate-decision-of-embryonic-stem-cells
#7
Zhong-Yan Chen, Fei Chen, Nan Cao, Zhi-Wen Zhou, Huang-Tian Yang
MicroRNAs (miRNAs) play important roles in cell fate decisions. However, the miRNAs and their targets involved in the regulation of cardiac lineage specification are largely unexplored. Here, we report novel functions of miR-142-3p in the regulation of cardiomyocyte differentiation from mouse embryonic stem cells (mESCs). With a miRNA array screen, we identified a number of miRNAs significantly changed during mESC differentiation into the mesodermal and cardiac progenitor cells, and miR-142-3p was one among the markedly downregulated miRNAs...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28631251/regulation-of-cardiac-myocyte-cell-death-and-differentiation-by-myocardin
#8
REVIEW
Joseph W Gordon
Myocardin is a cardiac- and smooth muscle-enriched transcriptional co-activator that was originally described as an interacting partner of the serum response factor. Shortly after myocardin's discovery, a wealth of published literature described the role of myocardin as a regulator of smooth muscle differentiation and phenotype modulation, while gene-targeting studies confirmed the essential role of myocardin in vascular development. More recently, myocardin has been implicated as an important regulator of cardiac myocyte differentiation in studies demonstrating direct programming of fibroblasts towards the cardiac lineage...
June 19, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28606231/-nkx2-5-and-tbx5-gene-mutations-in-in-vitro-fertilization-children-with-congenital-heart-disease
#9
Jing-Hui Yang, Xiao-Yan Xu, Hong-Ying Mi, Yan Jiang, Xin-Mei Ma, Li Li
OBJECTIVE: To explore the differences of NKX2.5 and TBX5 gene mutations between in vitro fertilization (IVF) children with congenital heart disease (CHD) and naturally conceived children with CHD. METHODS: Blood samples from 68 IVF children with CHD and 98 naturally conceived children with CHD were collected. The mutations in coding regions 1 and 2 of the NKX2.5 gene, and coding regions 4, 5, and 8 of the TBX5 gene were examined by polymerase chain reaction (PCR) and DNA sequencing...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28588211/transcription-factor-networks-derived-from-breast-cancer-stem-cells-control-the-immune-response-in-the-basal-subtype
#10
W A da Silveira, P V B Palma, R D Sicchieri, R A R Villacis, L R M Mandarano, T M G Oliveira, H M R Antonio, J M Andrade, V F Muglia, S R Rogatto, C Theillet, S du Manoir, D G Tiezzi
Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28580685/yy1-expression-is-sufficient-for-the-maintenance-of-cardiac-progenitor-cell-state
#11
Serge Gregoire, Guang Li, Anthony C Sturzu, Robert J Schwartz, Sean M Wu
During cardiac development, DNA binding transcription factors and epigenetic modifiers regulate gene expression in cardiac progenitor cells (CPCs). We have previously shown that Yin Yang 1 (YY1) is essential for the commitment of mesodermal precursors into CPCs. However, the role of YY1 in the maintenance of CPC phenotype and their differentiation into cardiomyocytes is unknown. In this study, we found, by genome-wide transcriptional profiling and phenotypic assays, that YY1 overexpression prevents cardiomyogenic differentiation and maintains the proliferative capacity of CPCs...
August 2017: Stem Cells
https://www.readbyqxmd.com/read/28576690/complement-component-c3ar-constitutes-a-novel-regulator-for-chick-eye-morphogenesis
#12
Erika Grajales-Esquivel, Agustin Luz-Madrigal, Jeffrey Bierly, Tracy Haynes, Edimara S Reis, Zeyu Han, Christian Gutierrez, Zachary McKinney, Apostolia Tzekou, John D Lambris, Panagiotis A Tsonis, Katia Del Rio-Tsonis
Complement components have been implicated in a wide variety of functions including neurogenesis, proliferation, cell migration, differentiation, cancer, and more recently early development and regeneration. Following our initial observations indicating that C3a/C3aR signaling induces chick retina regeneration, we analyzed its role in chick eye morphogenesis. During eye development, the optic vesicle (OV) invaginates to generate a bilayer optic cup (OC) that gives rise to the retinal pigmented epithelium (RPE) and neural retina...
August 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28570402/genetic-factors-involved-in-mandibular-prognathism
#13
Anna Doraczynska-Kowalik, Kamil H Nelke, Wojciech Pawlak, Maria M Sasiadek, Hanna Gerber
Mandibular prognathism is defined as an abnormal forward projection of the mandible beyond the standard relation to the cranial base and it is usually categorized as both a skeletal Class III pattern and Angle Class III malocclusion. The etiology of mandibular prognathism is still uncertain, with various genetic, epigenetic, and environmental factors possibly involved. However, many reports on its coexistence in both twins and segregation in families suggest the importance of genetic influences. A multifactorial and polygenic background with a threshold for expression or an autosomal dominant mode with incomplete penetrance and variable expressivity are the most probable inheritance patterns...
May 31, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28511407/gerbode-ventricular-septal-defect-a-rare-cardiac-anomaly-associated-with-genetic-variants-in-indian-population-a-case-series
#14
Yashvanthi Borkar, Krishnananda Nayak, Ranjan K Shetty, Gopalakrishna Bhat, Rajasekhar Moka
Gerbode defects are rare Ventricular Septal Defects (VSD) constituting approximately one percent cases of congenital heart diseases. The genetic predispositions towards the Gerbode Defect (GD) have remained an unexplored area of study till date. We investigated the genotype-phenotype correlation in patients with Gerbode VSD. Molecular genetic study on Sanger sequencing and subsequent data analysis showed that the contributing sequence variations in the NKX2-5, GATA4 and TBX5 gene lies in one of the highly conserved regions and this region is responsible for encoding a functional protein...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28469241/a-hand-to-tbx5-explains-the-link-between-thalidomide-and-cardiac-diseases
#15
Athar Khalil, Rachel Tanos, Nehmé El-Hachem, Mazen Kurban, Patrice Bouvagnet, Fadi Bitar, Georges Nemer
Congenital heart disease is the leading cause of death in the first year of life. Mutations only in few genes have been linked to some cases of CHD. Thalidomide was used by pregnant women for morning sickness but was removed from the market because it caused severe malformations including CHDs. We used both in silico docking software, and in vitro molecular and biochemical methods to document a novel interaction involving Thalidomide, TBX5, and HAND2. Thalidomide binds readily to TBX5 through amino acids R81, R82, and K226 all implicated in DNA binding...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28460022/korean-atrial-fibrillation-network-genome-wide-association-study-for-early-onset-atrial-fibrillation-identifies-novel-susceptibility-loci
#16
Ji-Young Lee, Tae-Hoon Kim, Pil-Sung Yang, Hong Euy Lim, Eue-Keun Choi, Jaemin Shim, Eunsoon Shin, Jae-Sun Uhm, Jin-Seok Kim, Boyoung Joung, Seil Oh, Moon-Hyoung Lee, Young-Hoon Kim, Hui-Nam Pak
Aims: Some genetic susceptibility loci for atrial fibrillation (AF) identified by genome-wide association studies (GWAS) in a European database showed ethnic differences in the Asian population. We explored novel AF susceptibility variants for patients with early-onset AF (≤60 years old) among Korean patients who underwent AF catheter ablation. Methods and results: A genome-wide association study (GWAS) was conducted with 672 cases (≤60 years old, Yonsei AF Ablation cohort) and 3700 controls (Korea Genome Epidemiology Study)...
April 27, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28434921/identification-of-a-novel-and-functional-mutation-in-the-tbx5-gene-in-a-patient-by-screening-from-354-patients-with-isolated-ventricular-septal-defect
#17
Huan-Xin Chen, Xi Zhang, Hai-Tao Hou, Jun Wang, Qin Yang, Xiu-Li Wang, Guo-Wei He
Ventricular septal defect (VSD) is the most frequently occurring congenital heart disease in newborns. A number of genetic studies have linked TBX5 mutations to cardiac abnormalities. We aimed to identify potential pathogenic mutations in TBX5 and to provide insights into the etiology of sporadic and isolated VSD. Case-control mutational and functional analyses were performed in 354 sporadic patients with isolated VSD and 341 controls. All the coding exons and intron-exon boundaries of TBX5 were first sequenced in a group of VSD patients and controls...
April 18, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28427897/boosters-and-barriers-for-direct-cardiac-reprogramming
#18
REVIEW
Mahmood Talkhabi, Elmira Rezaei Zonooz, Hossein Baharvand
Heart disease is currently the most significant cause of morbidity and mortality worldwide, which accounts for approximately 33% of all deaths. Recently, a promising and alchemy-like strategy has been developed called direct cardiac reprogramming, which directly converts somatic cells such as fibroblasts to cardiac lineage cells such as cardiomyocytes (CMs), termed induced CMs or iCMs. The first in vitro cardiac reprogramming study, mediated by cardiac transcription factors (TFs)-Gata4, Tbx5 and Mef2C-, was not enough efficient to produce an adequate number of fully reprogrammed, functional iCMs...
June 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28426026/generation-of-multipotent-induced-cardiac-progenitor-cells-from-mouse-fibroblasts-and-potency-testing-in-ex-vivo-mouse-embryos
#19
Pratik A Lalit, Adriana M Rodriguez, Karen M Downs, Timothy J Kamp
Here we describe a protocol to generate expandable and multipotent induced cardiac progenitor cells (iCPCs) from mouse adult fibroblasts using forced expression of Mesp1, Tbx5, Gata4, Nkx2.5 and Baf60c (MTGNB) along with activation of Wnt and JAK/STAT signaling. This method does not use iPS cell factors and thus differs from cell activation and signaling-directed (CASD) reprogramming to cardiac progenitors. Our method is specific to direct CPC reprogramming, whereas CASD reprogramming can generate various cell types depending on culture conditions and raises the possibility of transitioning through a pluripotent cell state...
May 2017: Nature Protocols
https://www.readbyqxmd.com/read/28362413/assessing-cardiomyocyte-subtypes-following-transcription-factor-mediated-reprogramming-of-mouse-embryonic-fibroblasts
#20
Antonio Fernandez-Perez, Nikhil V Munshi
Direct reprogramming of one cell type into another has recently emerged as a powerful paradigm for regenerative medicine, disease modeling, and lineage specification. In particular, the conversion of fibroblasts into induced cardiomyocyte-like myocytes (iCLMs) by Gata4, Hand2, Mef2c, and Tbx5 (GHMT) represents an important avenue for generating de novo cardiac myocytes in vitro and in vivo. Recent evidence suggests that GHMT generates a greater diversity of cardiac subtypes than previously appreciated, thus underscoring the need for a systematic approach to conducting additional studies...
March 22, 2017: Journal of Visualized Experiments: JoVE
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