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https://www.readbyqxmd.com/read/28427897/boosters-and-barriers-for-direct-cardiac-reprogramming
#1
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...
April 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28426816/ex-vivo-cultures-combined-with-vivo-morpholino-induced-gene-knockdown-provide-a-system-to-assess-the-role-of-wt1-and-gata4-during-gonad-differentiation
#2
Lucas J Rudigier, Christof Dame, Holger Scholz, Karin M Kirschner
Gonad morphogenesis relies on the correct spatiotemporal expression of a number of genes that together fulfill the differentiation of the bipotential gonad into testes or ovaries. As such, the transcription factors WT1 and GATA4 are pivotal for proper gonadal development. Here we address the contributions of GATA4 and WT1 to the sex differentiation phase in testes and ovaries. We applied an ex vivo technique for cultivating gonads in hanging droplets of media that were supplemented with vivo-morpholinos to knockdown WT1 and GATA4 either alone or in combination at the same developmental stage...
2017: PloS One
https://www.readbyqxmd.com/read/28426026/generation-of-multipotent-induced-cardiac-progenitor-cells-from-mouse-fibroblasts-and-potency-testing-in-ex-vivo-mouse-embryos
#3
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/28401730/dna-damage-and-senescence-in-osteoprogenitors-expressing-osx1-may-cause-their-decrease-with-age
#4
Ha-Neui Kim, Jianhui Chang, Lijian Shao, Li Han, Srividhya Iyer, Stavros C Manolagas, Charles A O'Brien, Robert L Jilka, Daohong Zhou, Maria Almeida
Age-related bone loss in mice results from a decrease in bone formation and an increase in cortical bone resorption. The former is accounted by a decrease in the number of postmitotic osteoblasts which synthesize the bone matrix and is thought to be the consequence of age-dependent changes in mesenchymal osteoblast progenitors. However, there are no specific markers for these progenitors, and conclusions rely on results from in vitro cultures of mixed cell populations. Moreover, the culprits of such changes remain unknown...
April 12, 2017: Aging Cell
https://www.readbyqxmd.com/read/28393293/gata4-regulates-osteoblastic-differentiation-and-bone-remodeling-via-p38-mediated-signaling
#5
Tingting Zhou, Shuyu Guo, Yuxin Zhang, Yajuan Weng, Lin Wang, Junqing Ma
Osteoblasts play a major role in bone remodeling and are regulated by transcription factors. GATA4, a zinc finger transcription factor from the GATA family, has an unclear role in osteoblast differentiation. In this study, the role of GATA4 in osteoblast differentiation was studied both in vitro and in vivo by GATA4 knockdown. GATA4 expression increased during osteoblast differentiation. GATA4 knockdown in osteoblast precursor cells reduced alkaline phosphatase activity and decreased the formation of calcified nodule in an osteogenic-induced cell culture system...
April 9, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28382690/epigallocatechin-gallate-reverses-ctni-low-expression-induced-age-related-heart-diastolic-dysfunction-through-histone-acetylation-modification
#6
Bo Pan, Junjun Quan, Lingjuan Liu, Zhongwei Xu, Jing Zhu, Xupei Huang, Jie Tian
Cardiac diastolic dysfunction (CDD) is the most common form of cardiovascular disorders, especially in elderly people. Cardiac troponin I (cTnI) plays a critical role in the regulation of cardiac function, especially diastolic function. Our previous studies showed that cTnI-low expression induced by histone acetylation modification might be one of the causes that result in diastolic dysfunction in ageing hearts. This study was designed to investigate whether epigallocatechin-3-gallate (EGCG) would modify histone acetylation events to regulate cTnI expression and then improve cardiac functions in ageing mice...
April 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28381408/rare-genetic-variants-in-gata-transcription-factors-in-patients-with-hypertrophic-cardiomyopathy
#7
Cristina Alonso-Montes, Julián Rodríguez-Reguero, María Martín, Juan Gómez, Eliecer Coto, Manuel Naves-Díaz, César Morís, Jorge B Cannata-Andía, Isabel Rodríguez
Hypertrophic cardiomyopathy (HCM) is a very heterogeneous disease. Although primarily caused by mutations in genes encoding sarcomeric proteins, other genes might explain that heterogeneity. Potential candidate genes are GATA transcription factors that regulate the expression of proteins associated with HCM. Exons of GATA2, GATA4, and GATA6 genes were sequenced in 212 patients with unrelated HCM previously analyzed for genes encoding the most frequently mutated sarcomeric proteins. Functional effects of variants were predicted by in silico analyses...
April 5, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28372585/multiple-gene-variations-contributed-to-congenital-heart-disease-via-gata-family-transcriptional-regulation
#8
Yanyan Qian, Deyong Xiao, Xiao Guo, Hongbo Chen, Lili Hao, Xiaojing Ma, Guoying Huang, Duan Ma, Huijun Wang
BACKGROUND: Congenital heart disease (CHD) is a common birth defect, and most cases occur sporadically. Mutations in key genes that are responsible for cardiac development could contribute to CHD. To date, the genetic causes of CHD remain largely unknown. METHODS: In this study, twenty-nine candidate genes in CHD were sequenced in 106 patients with Tetralogy of Fallot (TOF) using target exome sequencing (TES). The co-immunoprecipitation (CO-IP) and luciferase reporter gene assays were performed in HEK293T cells, and wild-type and mutant mRNA of ZFPM2 were microinjected into zebrafish embryos...
April 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28370166/mechanism-of-arsenite-toxicity-in-embryonic-stem-cells
#9
Naimisha Beeravolu, Christina McKee, G Rasul Chaudhry
Environmental arsenite exposure has been linked to cancer as well as other diseases, presenting an important and serious public health problem. Toxicity of inorganic arsenite (iAs) has been investigated using animal models and cell culture, yet its developmental effects are poorly understood. This study investigated the molecular mechanism of iAs toxicity to ascertain insight into development and differentiation processes using mouse embryonic stem cells (ESCs). The results showed that iAs exposure affected morphology and integrity of ESC colonies as well as inhibited cell growth in a concentration-dependent manner, excluding concentrations <1 μM iAs which stimulated ESC growth...
April 3, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28362413/assessing-cardiomyocyte-subtypes-following-transcription-factor-mediated-reprogramming-of-mouse-embryonic-fibroblasts
#10
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
https://www.readbyqxmd.com/read/28355297/transcription-factor-induced-activation-of-cardiac-gene-expression-in-human-c-kit-cardiac-progenitor-cells
#11
Tareq Al-Maqtari, Kyung U Hong, Bathri N Vajravelu, Afsoon Moktar, Pengxiao Cao, Joseph B Moore, Roberto Bolli
Although transplantation of c-kit+ cardiac progenitor cells (CPCs) significantly alleviates post-myocardial infarction left ventricular dysfunction, generation of cardiomyocytes by exogenous CPCs in the recipient heart has often been limited. Inducing robust differentiation would be necessary for improving the efficacy of the regenerative cardiac cell therapy. We assessed the hypothesis that differentiation of human c-kit+ CPCs can be enhanced by priming them with cardiac transcription factors (TFs). We introduced five different TFs (Gata4, MEF2C, NKX2...
2017: PloS One
https://www.readbyqxmd.com/read/28351621/critical-roles-of-astrin-in-the-mitosis-of-immature-rat-sertoli-cells
#12
Yuki Tochigi, Yuka Iwasaki, Masanori Sano, Hidenori Yasuda, Kentaro Katayama, Hiroetsu Suzuki
Male hypogonadism (hgn/hgn) rats show testicular hypoplasia accompanied by dysplastic development of seminiferous tubules due to loss-of-function mutation of the gene encoding Astrin, which is required for mitotic progression in the division cycle of HeLa cells. In the present study, we examined the cytological base leading to the decrease of Sertoli cells in hgn/hgn testes. In hgn/hgn testes on postnatal day 3, anti-phosphor-histone H3 (Ser10) (pH3)-positive mitotic phase and TUNEL-positive apoptosis increased in GATA4-positive Sertoli cells...
March 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28350043/hand1-loss-of-function-mutation-contributes-to-congenital-double-outlet-right-ventricle
#13
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...
January 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28349834/downregulation-of-transcription-factor-gata4-sensitizes-human-hepatoblastoma-cells-to-doxorubicin-induced-apoptosis
#14
Tea Soini, Marjut Pihlajoki, Antti Kyrönlahti, Leif C Andersson, David B Wilson, Markku Heikinheimo
Hepatoblastoma, the most common type of pediatric liver cancer, is treated with a combination of surgery and chemotherapy. An essential drug in the treatment of hepatoblastoma is doxorubicin, which in high doses is cardiotoxic. This adverse effect is due to downregulation of cardiac expression of transcription factor GATA4, leading in turn to diminished levels of anti-apoptotic BCL2 (B-cell lymphoma 2) protein family members. GATA4 is also expressed in early fetal liver, but absent from normal postnatal hepatocytes...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28336264/genomic-imbalances-in-syndromic-congenital-heart-disease
#15
Miriam Coelho Molck, Milena Simioni, Társis Paiva Vieira, Ilária Cristina Sgardioli, Fabíola Paoli Monteiro, Josiane Souza, Agnes Cristina Fett-Conte, Têmis Maria Félix, Isabella Lopes Monlléo, Vera Lúcia Gil-da-Silva-Lopes
OBJECTIVE: To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS). METHODS: 78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH) and/or multiplex ligation probe amplification (MLPA) were tested by chromosomal microarray analysis (CMA). RESULTS: Clinically significant copy number variations (CNVs ≥300kb) were identified in 10% (8/78) of cases...
March 21, 2017: Jornal de Pediatria
https://www.readbyqxmd.com/read/28303890/baf60b-mediated-atm-p53-activation-blocks-cell-identity-conversion-by-sensing-chromatin-opening
#16
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
#17
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
#18
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
#19
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
#20
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
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