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https://www.readbyqxmd.com/read/28197667/discovery-and-progress-of-direct-cardiac-reprogramming
#1
REVIEW
Hidenori Kojima, Masaki Ieda
Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs)...
February 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28164238/klf13-is-a-genetic-modifier-of-the-holt-oram-syndrome-gene-tbx5
#2
Rami Darwich, Wenjuan Li, Abir Yamak, Hiba Komati, Gregor Andelfinger, Kun Sun, Mona Nemer
No abstract text is available yet for this article.
February 6, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28111280/inhibition-of-gata4-and-tbx5-by-nicotine-mediated-dna-methylation-in-myocardial-differentiation
#3
Xue-Yan Jiang, Yu-Liang Feng, Li-Tong Ye, Xiao-Hong Li, Juan Feng, Meng-Zhen Zhang, Harnath S Shelat, Michael Wassler, Yangxin Li, Yong-Jian Geng, Xi-Yong Yu
Maternal nicotine exposure causes alteration of gene expression and cardiovascular programming. The discovery of nicotine-medicated regulation in cardiogenesis is of major importance for the study of cardiac defects. The present study investigated the effect of nicotine on cardiac gene expression and epigenetic regulation during myocardial differentiation. Persistent nicotine exposure selectively inhibited expression of two cardiac genes, Tbx5 and Gata4, by promoter DNA hypermethylation. The nicotine-induced suppression on cardiac differentiation was restored by general nicotinic acetylcholine receptor inhibition...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28109343/involvement-of-wnt-pathway-in-ethanol-induced-inhibition-of-mouse-embryonic-stem-cell-differentiation
#4
Qian Wang, Jing-Wen Song, Yang Liu, Xian-Xian Zhao
Ethanol has been reported to have toxicity on embryonic stem cells (ESCs). The present study aims to address the teratogenic effects of ethanol on the growth and cardiac differentiation of ESCs. Mouse embryonic stem D3 cells were employed. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were used to determine cytotoxicity. Quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting were used to analyze the expressions of cardiac differentiation-related and Wnt signaling factors...
February 2017: Alcohol
https://www.readbyqxmd.com/read/28100873/microrna-10a-targets-t-box-5-to-inhibit-the-development-of-cardiac-hypertrophy
#5
Dan Wang, Guanqun Zhai, Yangfei Ji, Haiyun Jing
The mechanism of cardiac hypertrophy involving microRNAs (miRNAs) is attracting increasing attention. Our study aimed to investigate the role of miR-10a in cardiac hypertrophy development and the underlying regulatory mechanism.Transverse abdominal aortic constriction (TAAC) surgery was performed to establish a cardiac hypertrophy rat model, and angiotensin II (AngII) was used to induce cardiac hypertrophy in cultured neonatal rat cardiomyocytes. Expression of T-box 5 (TBX5) and miR-10a was altered by cell transfection of siRNA or miRNA mimic/inhibitor...
February 7, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28071742/core-transcription-factors-micrornas-and-small-molecules-drive-transdifferentiation-of-human-fibroblasts-towards-the-cardiac-cell-lineage
#6
Nicolas Christoforou, Syandan Chakraborty, Robert D Kirkton, Andrew F Adler, Russell C Addis, Kam W Leong
Transdifferentiation has been described as a novel method for converting human fibroblasts into induced cardiomyocyte-like cells. Such an approach can produce differentiated cells to study physiology or pathophysiology, examine drug interactions or toxicities, and engineer cardiac tissues. Here we describe the transdifferentiation of human dermal fibroblasts towards the cardiac cell lineage via the induced expression of transcription factors GATA4, TBX5, MEF2C, MYOCD, NKX2-5, and delivery of microRNAs miR-1 and miR-133a...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28057270/the-roles-of-t-box-genes-in-vertebrate-limb-development
#7
C J Sheeba, M P O Logan
Members of the T-box gene family have diverse roles during embryogenesis and many play critical roles in the developing limb. This is exemplified by the fact that, in humans, mutations in T-box genes are associated with several congenital syndromes that include limb defects as part of their characteristic spectrum of abnormalities. T-box genes encode for evolutionary conserved transcription factors that include both transcriptional activators and repressors. The hallmark of T-box gene members is the presence of the eponymous DNA-binding T-box domain...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28057264/tbx5-a-key-regulator-of-heart-development
#8
J D Steimle, I P Moskowitz
TBX5 is a member of the T-box transcription factor family and is primarily known for its role in cardiac and forelimb development. Human patients with dominant mutations in TBX5 are characterized by Holt-Oram syndrome, and show defects of the cardiac septa, cardiac conduction system, and the anterior forelimb. The range of cardiac defects associated with TBX5 mutations in humans suggests multiple roles for the transcription factor in cardiac development and function. Animal models demonstrate similar defects and have provided a useful platform for investigating the roles of TBX5 during embryonic development...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28033319/correction-foxf-genes-integrate-tbx5-and-hedgehog-pathways-in-the-second-heart-field-for-cardiac-septation
#9
Andrew D Hoffmann, Xinan Holly Yang, Ozanna Burnicka-Turek, Joshua D Bosman, Xiaomeng Ren, Linglin Xie, Jeffrey D Steimle, Steven A Vokes, Andrew P McMahon, Vladimir V Kalinichenko, Ivan P Moskowitz
[This corrects the article DOI: 10.1371/journal.pgen.1004604.].
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27992425/tbx5-buffers-inherent-left-right-asymmetry-ensuring-symmetric-forelimb-formation
#10
Fatima A Sulaiman, Satoko Nishimoto, George R F Murphy, Anna Kucharska, Natalie C Butterfield, Ruth Newbury-Ecob, Malcolm P O Logan
The forelimbs and hindlimbs of vertebrates are bilaterally symmetric. The mechanisms that ensure symmetric limb formation are unknown but they can be disrupted in disease. In Holt-Oram Syndrome (HOS), caused by mutations in TBX5, affected individuals have left-biased upper/forelimb defects. We demonstrate a role for the transcription factor Tbx5 in ensuring the symmetric formation of the left and right forelimb. In our mouse model, bilateral hypomorphic levels of Tbx5 produces asymmetric forelimb defects that are consistently more severe in the left limb than the right, phenocopying the left-biased limb defects seen in HOS patients...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27984724/disease-model-of-gata4-mutation-reveals-transcription-factor-cooperativity-in-human-cardiogenesis
#11
Yen-Sin Ang, Renee N Rivas, Alexandre J S Ribeiro, Rohith Srivas, Janell Rivera, Nicole R Stone, Karishma Pratt, Tamer M A Mohamed, Ji-Dong Fu, C Ian Spencer, Nathaniel D Tippens, Molong Li, Anil Narasimha, Ethan Radzinsky, Anita J Moon-Grady, Haiyuan Yu, Beth L Pruitt, Michael P Snyder, Deepak Srivastava
Mutation of highly conserved residues in transcription factors may affect protein-protein or protein-DNA interactions, leading to gene network dysregulation and human disease. Human mutations in GATA4, a cardiogenic transcription factor, cause cardiac septal defects and cardiomyopathy. Here, iPS-derived cardiomyocytes from subjects with a heterozygous GATA4-G296S missense mutation showed impaired contractility, calcium handling, and metabolic activity. In human cardiomyocytes, GATA4 broadly co-occupied cardiac enhancers with TBX5, another transcription factor that causes septal defects when mutated...
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27958623/clinical-expression-of-holt-oram-syndrome-on-the-basis-of-own-clinical-experience-considering-prenatal-diagnosis
#12
Zofia Walencka, Aleksander Jamsheer, Piotr Surmiak, Małgorzata Baumert, Aleksandra Jezela-Stanek, Andrzej Witek, Anna Materna-Kiryluk, Anna Latos-Bieleńska, Magdalena Socha, Anna Sowińska-Seidler
OBJECTIVES: Holt-Oram syndrome manifests with defects of upper limbs, pectoral girdle and cardiovascular system. The aim of this paper was to present complex clinical picture of the syndrome and its variable expression on the example of the family diagnosed genetically on the neonatal ward, after proband's prenatal examination. MARETIAL AND METHODS: Nine family members were tested for TBX5 gene mutation. RESULTS: Four of family members were diagnosed with Holt-Oram syndrome and five had correct genetic test results...
2016: Ginekologia Polska
https://www.readbyqxmd.com/read/27930352/mir-590-promotes-transdifferentiation-of-porcine-and-human-fibroblasts-toward-a-cardiomyocyte-like-fate-by-directly-repressing-specificity-protein-1
#13
Vivek P Singh, Megumi Mathison, Vivekkumar Patel, Deepthi Sanagasetti, Brian W Gibson, Jianchang Yang, Todd K Rosengart
BACKGROUND: Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells represents a promising potential new therapy for treating heart disease, inducing significant improvements in postinfarct ventricular function in rodent models. Because reprogramming factors effective in transdifferentiating rodent cells are not sufficient to reprogram human cells, we sought to identify reprogramming factors potentially applicable to human studies. METHODS AND RESULTS: Lentivirus vectors expressing Gata4, Mef2c, and Tbx5 (GMT); Hand2 (H), Myocardin (My), or microRNA (miR)-590 were administered to rat, porcine, and human cardiac fibroblasts in vitro...
November 10, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27910042/direct-cardiac-reprogramming-as-a-novel-therapeutic-strategy-for-treatment-of-myocardial-infarction
#14
Hong Ma, Li Wang, Jiandong Liu, Li Qian
Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a novel therapy for the treatment of heart failure, a common and morbid disease that is usually caused by irreversible loss of functional cardiomyocytes (CMs). Recently, we and others showed that in a murine model of acute myocardial infarction, delivery of three transcription factors, Gata4, Mef2c, and Tbx5 converted endogenous cardiac fibroblasts into functional iCMs. These iCMs integrated electrically and mechanically with surrounding myocardium, resulting in a reduction in scar size and an improvement in heart function...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27834668/chemical-enhancement-of-in-vitro-and-in-vivo-direct-cardiac-reprogramming
#15
Tamer M A Mohamed, Nicole R Stone, Emily C Berry, Ethan Radzinsky, Yu Huang, Karishma Pratt, Yen-Sin Ang, Pengzhi Yu, Haixia Wang, Shibing Tang, Sergey Magnitsky, Sheng Ding, Kathryn N Ivey, Deepak Srivastava
BACKGROUND: -Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells (iCMs) in situ represents a promising strategy for cardiac regeneration. A combination of three cardiac transcription factors, Gata4, Mef2c and Tbx5 (GMT), can convert fibroblasts into iCMs, albeit with low efficiency in vitro METHODS: -We screened 5,500 compounds in primary cardiac fibroblasts to identify the pathways that can be modulated to enhance cardiomyocyte reprogramming. RESULTS: -We found that a combination of the transforming growth factor (TGF)-β inhibitor SB431542 and the WNT inhibitor XAV939 increased reprogramming efficiency eight-fold when added to GMT-overexpressing cardiac fibroblasts...
November 10, 2016: Circulation
https://www.readbyqxmd.com/read/27833996/expression-of-t-box-transcription-factors-2-4-and-5-is-decreased-in-the-branching-airway-mesenchyme-of-nitrofen-induced-hypoplastic-lungs
#16
Toshiaki Takahashi, Florian Friedmacher, Julia Zimmer, Prem Puri
PURPOSE: Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major therapeutic challenge in newborns with congenital diaphragmatic hernia (CDH). T-box transcription factors (Tbx) have been identified as key components of the gene network that regulates fetal lung development. Tbx2, Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung, regulating the process of lung branching morphogenesis. Furthermore, lungs of Tbx2-, Tbx4- and Tbx5-deficient mice are hypoplastic and exhibit decreased lung branching, similar to PH in human CDH...
November 11, 2016: Pediatric Surgery International
https://www.readbyqxmd.com/read/27819261/sirt1-deacetylates-the-cardiac-transcription-factor-nkx2-5-and-inhibits-its-transcriptional-activity
#17
Xiaoqiang Tang, Han Ma, Lei Han, Wei Zheng, Yun-Biao Lu, Xiao-Feng Chen, Shu-Ting Liang, Gong-Hong Wei, Zhu-Qin Zhang, Hou-Zao Chen, De-Pei Liu
The homeodomain transcription factor Nkx2.5/Csx is critically essential for heart specification, morphogenesis, and homeostasis. Acetylation/deacetylation is important for the localization, stability and activation of transcription factors. It remains unknown how Nkx2.5 is deacetylated and how Nkx2.5 acetylation determines its activity. In this study, we provide evidence that the NAD(+)-dependent class III protein deacetylase SIRT1 deacetylates Nkx2.5 in cardiomyocytes and represses the transcriptional activity of Nkx2...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27818139/cited2-cooperates-with-isl1-and-promotes-cardiac-differentiation-of-mouse-embryonic-stem-cells
#18
Ivette Pacheco-Leyva, Ana Catarina Matias, Daniel V Oliveira, João M A Santos, Rita Nascimento, Eduarda Guerreiro, Anna C Michell, Annebel M van De Vrugt, Gisela Machado-Oliveira, Guilherme Ferreira, Ibrahim Domian, José Bragança
The transcriptional regulator CITED2 is essential for heart development. Here, we investigated the role of CITED2 in the specification of cardiac cell fate from mouse embryonic stem cells (ESC). The overexpression of CITED2 in undifferentiated ESC was sufficient to promote cardiac cell emergence upon differentiation. Conversely, the depletion of Cited2 at the onset of differentiation resulted in a decline of ESC ability to generate cardiac cells. Moreover, loss of Cited2 expression impairs the expression of early mesoderm markers and cardiogenic transcription factors (Isl1, Gata4, Tbx5)...
December 13, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27773576/in-situ-reprogramming-to-transdifferentiate-fibroblasts-into-cardiomyocytes-using-adenoviral-vectors-implications-for-clinical-myocardial-regeneration
#19
Megumi Mathison, Vivek P Singh, Maria J Chiuchiolo, Deepthi Sanagasetti, Yun Mao, Vivekkumar B Patel, Jianchang Yang, Stephen M Kaminsky, Ronald G Crystal, Todd K Rosengart
OBJECTIVE: The reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells improves ventricular function in myocardial infarction models. Only integrating persistent expression vectors have thus far been used to induce reprogramming, potentially limiting its clinical applicability. We therefore tested the reprogramming potential of nonintegrating, acute expression adenoviral (Ad) vectors. METHODS: Ad or lentivirus vectors encoding Gata4 (G), Mef2c (M), and Tbx5 (T) were validated in vitro...
February 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27722056/life-threatening-cardiac-episode-in-a-polish-patient-carrying-contiguous-gene-microdeletion-of-the-tbx5-and-the-tbx3-genes
#20
Katarzyna Iwanicka-Pronicka, Magdalena Socha, Maria Jędrzejowska, Małgorzata Krajewska-Walasek, Aleksander Jamsheer
Holt-Oram syndrome (HOS) features radial ray hypoplasia, heart defect and cardiac conduction impairment. Ulnar-mammary syndrome (UMS) characterizes congenital defects of the ulnar side of the upper limbs, underdevelopment of apocrine glands including hypoplasia and the dysfunction of mammary glands, hypogonadism and obesity. Inheritance of both conditions is autosomal dominant, mutations or deletions are found in the TBX5 and TBX3 gene, respectively. The Polish patient presented short stature, obesity, congenital malformation of the radial and ulnar side of the upper limbs, heart block, hypogonadism and dysmorphic features...
2016: SpringerPlus
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