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https://www.readbyqxmd.com/read/29579079/enhanced-differentiation-of-human-pluripotent-stem-cells-into-cardiomyocytes-by-bacteria-mediated-transcription-factors-delivery
#1
Yongxin Jin, Ying Liu, Zhenpeng Li, Katherine Santostefano, Jing Shi, Xinwen Zhang, Donghai Wu, Zhihui Cheng, Weihui Wu, Naohiro Terada, Shouguang Jin, Fang Bai
Virus-mediated expression of defined transcription factor (TF) genes can effectively induce cellular reprogramming. However, sustained expression of the TFs often hinders pluripotent stem cell (PSC) differentiation into specific cell types, as each TF exerts its effect on PSCs for a defined period of time during differentiation. Here, we applied a bacterial type III secretion system (T3SS)-based protein delivery tool to directly translocate TFs in the form of protein into human PSCs. This transient protein delivery technique showed high delivery efficiency for hPSCs, and it avoids potential genetic alterations caused by the introduction of transgenes...
2018: PloS One
https://www.readbyqxmd.com/read/29574800/high-salt-induced-excess-reactive-oxygen-species-production-resulted-in-heart-tube-malformation-during-gastrulation
#2
Lin-Rui Gao, Guang Wang, Jing Zhang, Shuai Li, Manli Chuai, Yongping Bao, Berthold Hocher, Xuesong Yang
An association has been proved between high salt consumption and cardiovascular mortality. In vertebrates, the heart is the first functional organ to be formed. However, it is not clear whether high-salt exposure has an adverse impact on cardiogenesis. Here we report high-salt exposure inhibited basement membrane breakdown by affecting RhoA, thus disturbing the expression of Slug/E-cadherin/N-cadherin/Laminin and interfering with mesoderm formation during the epithelial-mesenchymal transition(EMT). Furthermore, the DiI+ cell migration trajectory in vivo and scratch wound assays in vitro indicated that high-salt exposure restricted cell migration of cardiac progenitors, which was caused by the weaker cytoskeleton structure and unaltered corresponding adhesion junctions at HH7...
March 25, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29565246/specialized-impulse-conduction-pathway-in-the-alligator-heart
#3
Bjarke Jensen, Bastiaan Jd Boukens, Dane A Crossley, Justin Conner, Rajiv Ahmet Mohan, Karel van Duijvenboden, Alex V Postma, Christopher R Gloschat, Ruth M Elsey, David Sedmera, Igor R Efimov, Vincent M Christoffels
Mammals and birds have a specialized cardiac atrioventricular conduction system enabling rapid activation of both ventricles. This system may have evolved together with high heart rates to support their endothermic state (warm-bloodedness), and is seemingly lacking in ectothermic vertebrates from which first mammals then birds independently evolved. Here, we studied the conduction system in crocodiles ( Alligator mississippiensis ), the only ectothermic vertebrates with a full ventricular septum. We identified homologues of mammalian conduction system markers ( Tbx3-Tbx5, Scn5a, Gja5, Nppa-Nppb ) and show the presence of a functional atrioventricular bundle...
March 22, 2018: ELife
https://www.readbyqxmd.com/read/29555671/a-screening-approach-to-identify-clinically-actionable-variants-causing-congenital-heart-disease-in-exome-data
#4
Justin O Szot, Hartmut Cuny, Gillian M Blue, David T Humphreys, Eddie Ip, Katrina Harrison, Gary F Sholler, Eleni Giannoulatou, Paul Leo, Emma L Duncan, Duncan B Sparrow, Joshua W K Ho, Robert M Graham, Nicholas Pachter, Gavin Chapman, David S Winlaw, Sally L Dunwoodie
BACKGROUND: Congenital heart disease (CHD)-structural abnormalities of the heart that arise during embryonic development-is the most common inborn malformation, affecting ≤1% of the population. However, currently, only a minority of cases can be explained by genetic abnormalities. The goal of this study was to identify disease-causal genetic variants in 30 families affected by CHD. METHODS: Whole-exome sequencing was performed with the DNA of multiple family members...
March 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29545482/genetic-control-of-left-atrial-gene-expression-yields-insights-into-the-genetic-susceptibility-for-atrial-fibrillation
#5
Jeffrey Hsu, Shamone Gore-Panter, Gregory Tchou, Laurie Castel, Beth Lovano, Christine S Moravec, Gosta B Pettersson, Eric E Roselli, A Marc Gillinov, Kenneth R McCurry, Nicholas G Smedira, John Barnard, David R Van Wagoner, Mina K Chung, Jonathan D Smith
BACKGROUND: Genome-wide association studies have identified 23 loci for atrial fibrillation (AF), but the mechanisms responsible for these associations, as well as the causal genes and genetic variants, remain undefined. METHODS: To identify the effect of common genetic variants on gene expression that might explain the mechanisms linking genome-wide association loci with AF risk, we performed RNA sequencing of left atrial appendages from a biracial cohort of 265 subjects...
March 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29545315/down-regulation-of-mir-10a-5p-promotes-proliferation-and-restricts-apoptosis-via-targeting-t-box-transcription-factor-5-in-inflamed-synoviocytes
#6
Nazim Hussain, Wenhua Zhu, Congshan Jiang, Jing Xu, Manman Geng, Xiaoying Wu, Safdar Hussain, Bo Wang, Muhammad Shahid Riaz Rajoka, Yue Li, Juan Tian, Liesu Meng, Shemin Lu
Synoviocytes from rheumatoid arthritis (RA) patients share certain features with tumor cells, such as over proliferation and invasion. Anomalous microRNA (miRNA) expression may participate in the pathogenesis of RA in different ways. The objective of this study was to observe the role of miR-10a-5p targeting TBX5 gene on synoviocyte proliferation and apoptosis in RA. Human synovial sarcoma cell line, SW982 cells stimulating with IL-1β were transfected with miR-10a-5p mimic and siRNA of TBX5. The real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis were used to evaluate the expression level of miR-10a-5p and TBX5 in SW982 cells, respectively...
March 15, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29542868/chemotherapy-and-terminal-skeletal-muscle-differentiation-in-wt1-mutant-wilms-tumors
#7
Brigitte Royer-Pokora, Manfred Beier, Artur Brandt, Constanze Duhme, Maike Busch, Carmen de Torres, Hans-Dieter Royer, Jaume Mora
Wilms tumors (WT) with WT1 mutations do not respond well to preoperative chemotherapy by volume reduction, suggesting resistance to chemotherapy. The histologic pattern of this tumor subtype indicates an intrinsic mesenchymal differentiation potential. Currently, it is unknown whether cytotoxic treatments can induce a terminal differentiation state as a direct comparison of untreated and chemotherapy-treated tumor samples has not been reported so far. We conducted gene expression profiling of 11 chemotherapy and seven untreated WT1-mutant Wilms tumors and analyzed up- and down-regulated genes with bioinformatic methods...
March 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29506474/anti-apoptotic-effects-of-igf-i-on-mortality-and-dysmorphogenesis-in-tbx5-deficient-zebrafish-embryos
#8
Tzu-Chun Tsai, Chun-Che Shih, Hsin-Ping Chien, An-Hang Yang, Jenn-Kan Lu, Jen-Her Lu
BACKGROUND: Tbx5 deficiency in zebrafish causes several abnormal phenotypes of the heart and pectoral fins. It has been reported that exogenous human growth hormone can enhance expression of downstream mediators in the growth hormone and insulin-like growth factor I (IGF-I) pathway and partially restore dysmorphogenesis in tbx5 morphants. This study aimed to further evaluate the effects of IGF-I on cell apoptosis and dysmorphogenesis in zebrafish embryos deficient for tbx5. RESULTS: Among the five studied groups of zebrafish embryos (wild-type embryos [WT], tbx5 morphants [MO], mismatched tbx5 morpholino-treated wild-type embryos [MIS], IGF-I-treated wild-type embryos [WTIGF1], and IGF-I-treated tbx5 morphants [MOIGF1]), the expression levels of the ifg1, igf1-ra, ifg-rb, erk1, and akt2 genes as well as the ERK and AKT proteins were significantly reduced in the MO group, but were partially restored in the MOIGF1 group...
March 5, 2018: BMC Developmental Biology
https://www.readbyqxmd.com/read/29490982/regulatory-integration-of-hox-factor-activity-with-tbox-factors-in-limb-development
#9
Deepak Jain, Stephen Nemec, Maëva Luxey, Yves Gauthier, Amandine Bemmo, Aurelio Balsalobre, Jacques Drouin
In tetrapods, Tbx4, Tbx5 and Hox cluster genes are crucial for forelimb and hindlimb development and mutations in these genes are responsible for congenital limb defects. The molecular basis of their integrated mechanisms of action in the context of limb development remains poorly understood. We studied Tbx4 and Hoxc10 due to their overlapping loss of function phenotypes and co-localized expression in hindlimb buds. We report an extensive overlap between Tbx4 and Hoxc10 genome occupancy and their putative target genes...
February 28, 2018: Development
https://www.readbyqxmd.com/read/29461882/genetic-analyses-identified-a-sall4-gene-mutation-associated-with-holt-oram-syndrome
#10
Bojian Li, Sun Chen, Kun Sun, Rang Xu, Yurong Wu
Holt-Oram syndrome (HOS) is an autosomal dominant disorder, which is characterized by deformities of upper limbs and congenital heart defects. Alterations of TBX5 gene have been identified to be the leading cause of HOS, while some cases could not be explained by TBX5 mutations. In our study, we preliminarily diagnosed a newborn baby, who had Tetralogy of Fallot, thumb agenesis, facial dysplasia, and right ear canal malformation, as HOS. Chromosome microarray analyses showed no pathological deletions or replications of chromosome segments; whole exome sequencing screened out six candidate genes that were involved in cardiac diseases or syndromes among which SALL4 has been reported as HOS related gene...
February 20, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29459676/genomic-variants-in-neurl-gja1-and-cux2-significantly-increase-genetic-susceptibility-to-atrial-fibrillation
#11
Pengxia Wang, Weixi Qin, Pengyun Wang, Yufeng Huang, Ying Liu, Rongfeng Zhang, Sisi Li, Qin Yang, Xiaojing Wang, Feifei Chen, Jingqiu Liu, Bo Yang, Xiang Cheng, Yuhua Liao, Yanxia Wu, Tie Ke, Xin Tu, Xiang Ren, Yanzong Yang, Yunlong Xia, Xiaoping Luo, Mugen Liu, He Li, Jingyu Liu, Yi Xiao, Qiuyun Chen, Chengqi Xu, Qing K Wang
Atrial fibrillation (AF) is the most common arrhythmia. In 2014, two new meta-GWAS identified 5 AF loci, including the NEURL locus, GJA1 locus, CAND2 locus, and TBX5 locus in the European ancestry populations and the NEURL locus and CUX2 locus in a Japanese population. The TBX5 locus for AF was reported by us in 2013 in the Chinese population. Here we assessed the association between AF and SNPs in the NEURL, GJA1, CAND2 and CUX2 loci in the Chinese Han population. We carried out a large case-control association study with 1,164 AF patients and 1,460 controls...
February 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29412738/reciprocity-of-action-of-increasing-oct4-and-repressing-p53-in-transdifferentiation-of-mouse-embryonic-fibroblasts-into-cardiac-myocytes
#12
Hongran Wang, Shuying Zhao, Michelle Barton, Todd Rosengart, Austin J Cooney
p53 is a barrier to somatic cell reprogramming. Deletion or transient suppression of p53 increases the efficiency of reprogramming of somatic cells into induced pluripotent stem cells. Whether p53 represents an obstacle to a similar process transdifferentiation of somatic cells is unknown. However, it is predicted that inhibition of p53 would promote transdifferentiation of fibroblasts into cardiomyocytes. In this study, the effect of p53 on the capacity of cardiogenic transdifferentiation is evaluated using p53 wild-type (p53+/+ ), p53 heterozygous mutant (p53+/- ), and p53 homozygous mutant (p53-/- ) mouse embryonic fibroblasts (MEFs)...
February 2018: Cellular Reprogramming
https://www.readbyqxmd.com/read/29377175/the-effect-of-maternal-exposure-to-di-2-ethylhexyl-phthalate-on-fetal-cardiac-development-in-mice
#13
Changqing Tang, Yuxin Deng, Hongyu Duan, Yi Zhang, Yifei Li, Dajian Qiu, Kaiyu Zhou, Yimin Hua, Chuan Wang
Accumulating evidence has suggested a link between maternal di-(2-ethylhexyl)-phthalate (DEHP) exposure and various developmental abnormalities. However, the evidence regarding the effect of maternal DEHP exposure on fetal cardiac development is scarce. The present study aimed to determine the effect of maternal DEHP exposure on fetal cardiac development in mice and explore the possible involved mechanism preliminarily. The C57BL mice were randomly divided into four groups: the vehicle group (corn oil, n = 10), 250 mg kg-1 DEHP group (n = 15), 500 mg kg-1 DEHP group (n = 20) and 1 g kg-1 DEHP group (n = 20)...
June 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29373717/integrated-transcriptomic-and-regulatory-network-analyses-identify-microrna-200c-as-a-novel-repressor-of-human-pluripotent-stem-cell-derived-cardiomyocyte-differentiation-and-maturation
#14
Ellen Ngar Yun Poon, Baixia Hao, Daogang Guan, Mulin Jun Li, Jun Lu, Yong Yang, Binbin Wu, Stanley Chun Ming Wu, Sarah E Webb, Yan Liang, Andrew L Miller, Xiaoqiang Yao, Junwen Wang, Bin Yan, Kenneth R Boheler
Aims: MicroRNAs (miRNAs) are crucial for the post-transcriptional control of protein-encoding genes, and together with transcription factors (TFs) regulate gene expression; however, the regulatory activities of miRNAs during cardiac development are only partially understood. In this study, we tested the hypothesis that integrative computational approaches could identify miRNAs that experimentally could be shown to regulate cardiomyogenesis. Methods and results: We integrated expression profiles with bioinformatics analyses of miRNA and TF regulatory programs to identify candidate miRNAs involved with cardiac development...
January 24, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29316729/wnt-rspo-and-hippo-signalling-in-the-intestine-and-intestinal-stem-cells
#15
REVIEW
Vitezslav Kriz, Vladimir Korinek
In this review, we address aspects of Wnt, R-Spondin (RSPO) and Hippo signalling, in both healthy and transformed intestinal epithelium. In intestinal stem cells (ISCs), the Wnt pathway is essential for intestinal crypt formation and renewal, whereas RSPO-mediated signalling mainly affects ISC numbers. In human colorectal cancer (CRC), aberrant Wnt signalling is the driving mechanism initiating this type of neoplasia. The signalling role of the RSPO-binding transmembrane proteins, the leucine-rich-repeat-containing G-protein-coupled receptors (LGRs), is possibly more pleiotropic and not only limited to the enhancement of Wnt signalling...
January 8, 2018: Genes
https://www.readbyqxmd.com/read/29280435/transcription-factor-dependent-enhancer-transcription-defines-a-gene-regulatory-network-for-cardiac-rhythm
#16
Xinan H Yang, Rangarajan D Nadadur, Catharina Re Hilvering, Valerio Bianchi, Michael Werner, Stefan R Mazurek, Margaret Gadek, Kaitlyn M Shen, Joseph Aaron Goldman, Leonid Tyan, Jenna Bekeny, Johnathon M Hall, Nutishia Lee, Carlos Perez-Cervantes, Ozanna Burnicka-Turek, Kenneth D Poss, Christopher R Weber, Wouter de Laat, Alexander J Ruthenburg, Ivan P Moskowitz
The noncoding genome is pervasively transcribed. Noncoding RNAs (ncRNAs) generated from enhancers have been proposed as a general facet of enhancer function and some have been shown to be required for enhancer activity. Here we examine the transcription-factor-(TF)-dependence of ncRNA expression to define enhancers and enhancer-associated ncRNAs that are involved in a TF-dependent regulatory network. TBX5, a cardiac TF, regulates a network of cardiac channel genes to maintain cardiac rhythm. We deep sequenced wildtype and Tbx5 -mutant mouse atria, identifying ~2600 novel Tbx5 -dependent ncRNAs...
December 27, 2017: ELife
https://www.readbyqxmd.com/read/29276141/direct-in-vivo-reprogramming-with-sendai-virus-vectors-improves-cardiac-function-after-myocardial-infarction
#17
Kazutaka Miyamoto, Mizuha Akiyama, Fumiya Tamura, Mari Isomi, Hiroyuki Yamakawa, Taketaro Sadahiro, Naoto Muraoka, Hidenori Kojima, Sho Haginiwa, Shota Kurotsu, Hidenori Tani, Li Wang, Li Qian, Makoto Inoue, Yoshinori Ide, Junko Kurokawa, Tsunehisa Yamamoto, Tomohisa Seki, Ryo Aeba, Hiroyuki Yamagishi, Keiichi Fukuda, Masaki Ieda
Direct cardiac reprogramming holds great promise for regenerative medicine. We previously generated directly reprogrammed induced cardiomyocyte-like cells (iCMs) by overexpression of Gata4, Mef2c, and Tbx5 (GMT) using retrovirus vectors. However, integrating vectors pose risks associated with insertional mutagenesis and disruption of gene expression and are inefficient. Here, we show that Sendai virus (SeV) vectors expressing cardiac reprogramming factors efficiently and rapidly reprogram both mouse and human fibroblasts into integration-free iCMs via robust transgene expression...
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29250101/perspective-is-random-monoallelic-expression-a-contributor-to-phenotypic-variability-of-autosomal-dominant-disorders
#18
Baoheng Gui, Jesse Slone, Taosheng Huang
Several factors have been proposed as contributors to interfamilial and intrafamilial phenotypic variability in autosomal dominant disorders, including allelic variation, modifier genes, environmental factors and complex genetic and environmental interactions. However, regardless of the similarity of genetic background and environmental factors, asymmetric limb or trunk anomalies in a single individual and variable manifestation between monozygotic twins have been observed, indicating other mechanisms possibly involved in expressivity of autosomal dominant diseases...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29221486/a-screening-system-to-identify-transcription-factors-that-induce-binding-site-directed-dna-demethylation
#19
Takahiro Suzuki, Shiori Maeda, Erina Furuhata, Yuri Shimizu, Hajime Nishimura, Mami Kishima, Harukazu Suzuki
BACKGROUND: DNA methylation is a fundamental epigenetic modification that is involved in many biological systems such as differentiation and disease. We and others recently showed that some transcription factors (TFs) are involved in the site-specific determination of DNA demethylation in a binding site-directed manner, although the reports of such TFs are limited. RESULTS: Here, we develop a screening system to identify TFs that induce binding site-directed DNA methylation changes...
December 8, 2017: Epigenetics & Chromatin
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
#20
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...
January 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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