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https://www.readbyqxmd.com/read/28303890/baf60b-mediated-atm-p53-activation-blocks-cell-identity-conversion-by-sensing-chromatin-opening
#1
Shuyi Ji, Linying Zhu, Yimeng Gao, Xiaoran Zhang, Yupeng Yan, Jin Cen, Rongxia Li, Rong Zeng, Lujian Liao, Chunhui Hou, Yawei Gao, Shaorong Gao, Gang Wei, Lijian Hui
Lineage conversion by expression of lineage-specific transcription factors is a process of epigenetic remodeling that has low efficiency. The mechanism by which a cell resists lineage conversion is largely unknown. Using hepatic-specific transcription factors Foxa3, Hnf1α and Gata4 (3TF) to induce hepatic conversion in mouse fibroblasts, we showed that 3TF induced strong activation of the ATM-p53 pathway, which led to proliferation arrest and cell death, and it further prevented hepatic conversion. Notably, ATM activation, independent of DNA damage, responded to chromatin opening during hepatic conversion...
March 17, 2017: Cell Research
https://www.readbyqxmd.com/read/28296881/transcriptomic-responses-to-environmental-temperature-by-turtles-with-temperature-dependent-and-genotypic-sex-determination-assessed-by-rnaseq-inform-the-genetic-architecture-of-embryonic-gonadal-development
#2
Srihari Radhakrishnan, Robert Literman, Jennifer Neuwald, Andrew Severin, Nicole Valenzuela
Vertebrate sexual fate is decided primarily by the individual's genotype (GSD), by the environmental temperature during development (TSD), or both. Turtles exhibit TSD and GSD, making them ideal to study the evolution of sex determination. Here we analyze temperature-specific gonadal transcriptomes (RNA-sequencing validated by qPCR) of painted turtles (Chrysemys picta TSD) before and during the thermosensitive period, and at equivalent stages in soft-shell turtles (Apalone spinifera-GSD), to test whether TSD's and GSD's transcriptional circuitry is identical but deployed differently between mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28296184/long-term-administration-of-pyridostigmine-attenuates-pressure-overload-induced-cardiac-hypertrophy-by-inhibiting-calcineurin-signalling
#3
Yi Lu, Ming Zhao, Jin-Jun Liu, Xi He, Xiao-Jiang Yu, Long-Zhu Liu, Lei Sun, Li-Na Chen, Wei-Jin Zang
Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms...
March 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28262548/notch-inhibition-enhances-cardiac-reprogramming-by-increasing-mef2c-transcriptional-activity
#4
Maria Abad, Hisayuki Hashimoto, Huanyu Zhou, Maria Gabriela Morales, Beibei Chen, Rhonda Bassel-Duby, Eric N Olson
Conversion of fibroblasts into functional cardiomyocytes represents a potential means of restoring cardiac function after myocardial infarction, but so far this process remains inefficient and little is known about its molecular mechanisms. Here we show that DAPT, a classical Notch inhibitor, enhances the conversion of mouse fibroblasts into induced cardiac-like myocytes by the transcription factors GATA4, HAND2, MEF2C, and TBX5. DAPT cooperates with AKT kinase to further augment this process, resulting in up to 70% conversion efficiency...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28242277/assessing-the-toxicity-of-triphenyltin-to-different-life-stages-of-the-marine-medaka-oryzias-melastigma-through-a-series-of-life-cycle-based-experiments
#5
Xianliang Yi, Kenneth M Y Leung
Toxic effects of triphenyltin (TPT) to different life stages of the marine medaka Oryzias melastigma were investigated through a series of life-cycle based exposure experiments. In embryo stage, TPT exposure could elevate the heartbeat rate at Day 6-8 post-fertilization and increase the expression levels of five heart development related genes (i.e., ATPase, COX2, BMP4, GATA4 and NKX2.5). In larval stage, TPT shortened the body length at ≥10μg/L and suppressed the swimming activity of the fish larvae at Day 1 post-hatching at 50μg/L...
February 24, 2017: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28241454/next-generation-sequencing-approach-in-methylation-analysis-of-hnf1b-and-gata4-genes-searching-for-biomarkers-in-ovarian-cancer
#6
Ivana Bubancova, Helena Kovarikova, Jan Laco, Ema Ruszova, Ondrej Dvorak, Vladimir Palicka, Marcela Chmelarova
DNA methylation is well-known to be associated with ovarian cancer (OC) and has great potential to serve as a biomarker in monitoring response to therapy and for disease screening. The purpose of this study was to investigate methylation of HNF1B and GATA4 and correlate detected methylation with clinicopathological characteristic of OC patients. The study group consisted of 64 patients with OC and 35 control patients. To determine the most important sites of HNF1B and GATA4, we used next-generation sequencing...
February 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218627/gata4-dependent-organ-specific-endothelial-differentiation-controls-liver-development-and-embryonic-hematopoiesis
#7
Cyrill Géraud, Philipp-Sebastian Koch, Johanna Zierow, Kay Klapproth, Katrin Busch, Victor Olsavszky, Thomas Leibing, Alexandra Demory, Friederike Ulbrich, Miriam Diett, Sandhya Singh, Carsten Sticht, Katja Breitkopf-Heinlein, Karsten Richter, Sanna-Maria Karppinen, Taina Pihlajaniemi, Bernd Arnold, Hans-Reimer Rodewald, Hellmut G Augustin, Kai Schledzewski, Sergij Goerdt
Microvascular endothelial cells (ECs) are increasingly recognized as organ-specific gatekeepers of their microenvironment. Microvascular ECs instruct neighboring cells in their organ-specific vascular niches through angiocrine factors, which include secreted growth factors (angiokines), extracellular matrix molecules, and transmembrane proteins. However, the molecular regulators that drive organ-specific microvascular transcriptional programs and thereby regulate angiodiversity are largely elusive. In contrast to other ECs, which form a continuous cell layer, liver sinusoidal ECs (LSECs) constitute discontinuous, permeable microvessels...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28218626/building-discontinuous-liver-sinusoidal-vessels
#8
Courtney T Griffin, Siqi Gao
Blood vessels have a unified mission to circulate blood throughout the body; however, they have additional diverse and specialized roles in various organs. For example, in the liver, discontinuous sinusoids, which are fenestrated capillaries with intercellular gaps and a fragmented basement membrane, facilitate delivery of macromolecules to highly metabolic hepatocytes. During embryonic development, discontinuous sinusoids also allow circulating hematopoietic progenitor and stem cells to populate the liver and promote blood cell differentiation...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28205629/mechanisms-of-chinese-medicine-xinmailong-s-protection-against-heart-failure-in-pressure-overloaded-mice-and-cultured-cardiomyocytes
#9
Jianyong Qi, Juan Yu, Yafang Tan, Renshan Chen, Wen Xu, Yanfen Chen, Jun Lu, Qin Liu, Jiashin Wu, Weiwang Gu, Minzhou Zhang
Patients with heart failure (HF) have high mortality and mobility. Xinmailong (XML) injection, a Chinese Medicine, is clinically effective in treating HF. However, the mechanism of XML's effectiveness on HF was unclear, and thus, was the target of the present study. We created a mouse model of pressure-overload-induced HF with transverse aortic constriction (TAC) surgery and compared among 4 study groups: SHAM (n = 10), TAC (n = 12), MET (metoprolol, positive drug treatment, n = 7) and XML (XML treatment, n = 14)...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197667/discovery-and-progress-of-direct-cardiac-reprogramming
#10
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/28196600/genome-editing-in-hpscs-reveals-gata6-haploinsufficiency-and-a-genetic-interaction-with-gata4-in-human-pancreatic-development
#11
Zhong-Dong Shi, Kihyun Lee, Dapeng Yang, Sadaf Amin, Nipun Verma, Qing V Li, Zengrong Zhu, Chew-Li Soh, Ritu Kumar, Todd Evans, Shuibing Chen, Danwei Huangfu
Human disease phenotypes associated with haploinsufficient gene requirements are often not recapitulated well in animal models. Here, we have investigated the association between human GATA6 haploinsufficiency and a wide range of clinical phenotypes that include neonatal and adult-onset diabetes using CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9-mediated genome editing coupled with human pluripotent stem cell (hPSC) directed differentiation. We found that loss of one GATA6 allele specifically affects the differentiation of human pancreatic progenitors from the early PDX1+ stage to the more mature PDX1+NKX6...
February 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28167794/gata4-potentiates-second-heart-field-proliferation-and-hedgehog-signaling-for-cardiac-septation
#12
Lun Zhou, Jielin Liu, Menglan Xiang, Patrick Olson, Alexander Guzzetta, Ke Zhang, Ivan P Moskowitz, Linglin Xie
GATA4, an essential cardiogenic transcription factor, provides a model for dominant transcription factor mutations in human disease. Dominant GATA4 mutations cause congenital heart disease (CHD), specifically atrial and atrioventricular septal defects (ASDs and AVSDs). We found that second heart field (SHF)-specific Gata4 heterozygote embryos recapitulated the AVSDs observed in germline Gata4 heterozygote embryos. A proliferation defect of SHF atrial septum progenitors and hypoplasia of the dorsal mesenchymal protrusion, rather than anlage of the atrioventricular septum, were observed in this model...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28161810/mutation-screening-of-gata4-gene-in-ctd-patients-within-chinese-han-population
#13
Yang Liu, Bojian Li, Yuejuan Xu, Kun Sun
Conotruncal heart defect is a complex form of congenital heart disease and usually has a poor prognosis. Although previous studies have identified several missense variants in GATA4 gene that may cause CTD, it remains unclear whether they are involved in CTD pathogenesis because the study population was limited. The aim of the study was to investigate the mutations of GATA4 gene in isolated CTD Chinese Han patients and identify the pathomechanism of the missense mutations. In this report, the coding exons and exon-intron boundaries of the GATA4 gene were sequenced in 600 CTD patients and 300 controls...
February 4, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28152522/generation-and-characteristics-of-human-sertoli-cell-line-immortalized-by-overexpression-of-human-telomerase
#14
Liping Wen, Qingqing Yuan, Min Sun, Minghui Niu, Hong Wang, Hongyong Fu, Fan Zhou, Chencheng Yao, Xiaobo Wang, Zheng Li, Zuping He
Sertoli cells are required for normal spermatogenesis and they can be reprogrammed to other types of functional cells. However, the number of primary Sertoli cells is rare and human Sertoli cell line is unavailable. In this study, we have for the first time reported a stable human Sertoli cell line, namely hS1 cells, by overexpression of human telomerase. The hS1 cells expressed a number of hallmarks for human Sertoli cells, including SOX9, WT1, GDNF, SCF, BMP4, BMP6, GATA4, and VIM, and they were negative for 3β-HSD, SMA, and VASA...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28138261/the-effects-of-exercise-training-and-caloric-restriction-on-the-cardiac-oxytocin-natriuretic-peptide-system-in-the-diabetic-mouse
#15
Tom L Broderick, Marek Jankowski, Jolanta Gutkowska
BACKGROUND: Regular exercise training (ET) and caloric restriction (CR) are the frontline strategies in the treatment of type 2 diabetes mellitus with the aim at reducing cardiometabolic risk. ET and CR improve body weight and glycemic control, and experimental studies indicate that these paradigms afford cardioprotection. In this study, the effects of combined ET and CR on the cardioprotective oxytocin (OT)-natriuretic peptide (NP) system were determined in the db/db mouse, a model of type 2 diabetes associated with insulin resistance, hyperglycemia, and obesity...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28135716/overexpression-of-cardiac-specific-kinase-tnni3k-promotes-mouse-embryonic-stem-cells-differentiation-into-cardiomyocytes
#16
Yin Wang, Shi-Qiang Wang, Li-Peng Wang, Yu-Hong Yao, Chun-Yan Ma, Jin-Feng Ding, Jue Ye, Xian-Min Meng, Rui-Xia Xu, Jian-Jun Li
Backgroud/Aims: The biological function of cardiac troponin I-interacting kinase (TNNI3K), a cardiac-specific functional kinase, is largely unknown. We investigated the effect of human TNNI3K (hTNNI3K) on the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes. METHODS: First, the time-space expression of endogenous Tnni3k was detected by real-time polymerase chain reaction (PCR) and western blotting at 16 different time-points over a period of 28 days. Further, action potentials and calcium current with/without 5 µM nifedipine were measured by patch clamp for mESC-derived cardiomyocytes...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28131743/novel-genes-involved-in-pathophysiology-of-gonadotropin-dependent-adrenal-tumors-in-mice
#17
Milena Doroszko, Marcin Chrusciel, Kirstine Belling, Susanna Vuorenoja, Marlene Dalgaard, Henrik Leffers, H Bjørn Nielsen, Ilpo Huhtaniemi, Jorma Toppari, Nafis A Rahman
Specific inbred strains and transgenic inhibin-α Simian Virus 40 T antigen (inhα/Tag) mice are genetically susceptible to gonadectomy-induced adrenocortical neoplasias. We identified altered gene expression in prepubertally gonadectomized (GDX) inhα/Tag and wild-type (WT) mice. Besides earlier reported Gata4 and Lhcgr, we found up-regulated Esr1, Prlr-rs1, and down-regulated Grb10, Mmp24, Sgcd, Rerg, Gnas, Nfatc2, Gnrhr, Igf2 in inhα/Tag adrenal tumors. Sex-steroidogenic enzyme genes expression (Srd5a1, Cyp19a1) was up-regulated in tumors, but adrenal-specific steroidogenic enzyme (Cyp21a1, Cyp11b1, Cyp11b2) down-regulated...
January 25, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28115595/effect-of-lithium-on-ventricular-remodeling-in-infarcted-rats-via-the-akt-mtor-signaling-pathways
#18
Tsung-Ming Lee, Shinn-Zong Lin, Nen-Chung Chang
Activation of phosphoinositide 3-kinase/Akt signaling is the molecular pathway driving physiological hypertrophy. As lithium, a phosphoinositide 3-kinase agonist, is highly toxic at regular doses, we assessed the effect of lithium at a low dose on ventricular hypertrophy after myocardial infarction.  Male Wistar rats after induction of myocardial infarction were randomized to either vehicle or lithium (1 mmol/kg per day) for 4 weeks. The dose of lithium led to a mean serum level of 0.39 mM, substantially lower than therapeutic concentrations (0...
January 23, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28112363/hand1-loss-of-function-mutation-contributes-to-congenital-double-outlet-right-ventricle
#19
Li Li, Juan Wang, Xing-Yuan Liu, Hua Liu, Hong-Yu Shi, Xiao-Xiao Yang, Ning Li, Yan-Jie Li, Ri-Tai Huang, Song Xue, Xing-Biao Qiu, Yi-Qing Yang
Congenital heart defects (CHDs), a wide variety of developmental abnormalities in the structures of the heart and the great thoracic blood vessels, are the most common form of birth defect in humans worldwide. CHDs are accountable for substantial morbidity and are still the leading cause of birth defect‑related deaths. Recent studies have demonstrated the pivotal roles of genetic defects in the pathogenesis of CHDs, and a great number of genetic mutations have been associated with CHDs. Nevertheless, CHDs are a genetically heterogeneous disorder and the genetic basis underlying CHDs in an overwhelming majority of cases remains unclear...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28111280/inhibition-of-gata4-and-tbx5-by-nicotine-mediated-dna-methylation-in-myocardial-differentiation
#20
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
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