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https://www.readbyqxmd.com/read/28381408/rare-genetic-variants-in-gata-transcription-factors-in-patients-with-hypertrophic-cardiomyopathy
#1
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/28380430/novel-rna-biomarkers-of-prostate-cancer-revealed-by-rna-seq-analysis-of-formalin-fixed-samples-obtained-from-russian-patients
#2
Anastasia S Nikitina, Elena I Sharova, Svetlana A Danilenko, Tatiana B Butusova, Alexandr O Vasiliev, Alexandr V Govorov, Elena A Prilepskaya, Dmitry Y Pushkar, Elena S Kostryukova
Due to heterogeneous multifocal nature of prostate cancer (PCa), there is currently a lack of biomarkers that stably distinguish it from benign prostatic hyperplasia (BPH), predict clinical outcome and guide the choice of optimal treatment. In this study RNA-seq analysis was applied to formalin-fixed paraffin-embedded (FFPE) tumor and matched normal tissue samples collected from Russian patients with PCa and BPH. We identified 3384 genes differentially expressed (DE) (FDR < 0.05) between tumor tissue of PCa patients and adjacent normal tissue as well as both tissue types from BPH patients...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28298438/single-cell-analysis-reveals-lineage-segregation-in-early-post-implantation-mouse-embryos
#3
Jing Wen, Yanwu Zeng, Zhuoqing Fang, Junjie Gu, Laixiang Ge, Fan Tang, Zepeng Qu, Jing Hu, Yaru Cui, Kunshan Zhang, Junbang Wang, Siguang Li, Yi Sun, Ying Jin
The mammalian post-implantation embryo has been extensively investigated at the tissue level. However, to unravel the molecular basis for the cell-fate plasticity and determination, it is essential to study the characteristics of individual cells. Especially, the individual definitive endoderm (DE) cells have not been characterized in vivo. Here, we report gene expression patterns in single cells freshly isolated from mouse embryos on days 5.5 and 6.5. Initial transcriptome data from 124 single cells yielded signature genes for the epiblast, visceral endoderm, and extra-embryonic ectoderm and revealed a unique distribution pattern of fibroblast growth factor (Fgf) ligands and receptors...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28275215/roles-of-gata6-during-gonadal-development-in-japanese-flounder-gonadogenesis-regulation-of-gender-related-genes-estrogen-formation-and-gonadal-function-maintenance
#4
Zan Li, Xiumei Liu, Yan Sun, Jinxiang Liu, Yuezhong Liu, Mengxun Wang, Quanqi Zhang, Xubo Wang
GATA-binding protein 6 (GATA6), a highly-conserved transcription factor of the GATA family plays an important role in gonadal cell proliferation, differentiation and endoderm development. In this study, the full-length cDNA of GATA6 of Paralichthys olivaceus (Japanese flounder) was obtained. Phylogenetic, gene structure and synteny analyses demonstrated that GATA6 of P. olivaceus is homologous to that of teleosts and tetrapods. The P. olivaceus GATA6 transcript showed higher expression in testis than in ovary, demonstrating a sexually dimorphic gene expression...
January 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28270130/mir-124-targets-gata6-to-suppress-cholangiocarcinoma-cell-invasion-and-metastasis
#5
Feng Tian, Jian Chen, Shuguo Zheng, Dajiang Li, Xin Zhao, Peng Jiang, Jianwei Li, Shuguang Wang
BACKGROUND: Our previous study showed that GATA6 plays important roles in cholangiocarcinoma (CCA) cell invasion and metastasis. However, the regulation mechanism of GATA6 in CCA is not clear. In this study, we studied the potential function of miR-124 in CCA and the mechanism of GATA6 regulation. METHODS: The expression levels of miR-124 and GATA6 in cancerous tissues from 57 CCA patients was detected by RT-PCR and IHC. The impact of miR-124 on GATA6 expression in CCA cells was evaluated using cell transfection, xenotransplantation into nude mice and a luciferase reporter assay...
March 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28236165/mechanosensitive-microrna-181b-regulates-aortic-valve-endothelial-matrix-degradation-by-targeting-timp3
#6
Jack M Heath, Joan Fernandez Esmerats, Lucky Khambouneheuang, Sandeep Kumar, Rachel Simmons, Hanjoong Jo
Calcific aortic valve disease (CAVD) is a major cause of morbidity in the aging population, but the underlying mechanisms of its progression remain poorly understood. Aortic valve calcification preferentially occurs on the fibrosa, which is subjected to disturbed flow. The side-specific progression of the disease is characterized by inflammation, calcific lesions, and extracellular matrix (ECM) degradation. Here, we explored the role of mechanosensitive microRNA-181b and its downstream targets in human aortic valve endothelial cells (HAVECs)...
February 24, 2017: Cardiovascular Engineering and Technology
https://www.readbyqxmd.com/read/28196690/gata6-plays-an-important-role-in-the-induction-of-human-definitive-endoderm-development-of-the-pancreas-and-functionality-of-pancreatic-%C3%AE-%C3%A2-cells
#7
Amita Tiyaboonchai, Fabian L Cardenas-Diaz, Lei Ying, Jean Ann Maguire, Xiuli Sim, Chintan Jobaliya, Alyssa L Gagne, Siddharth Kishore, Diana E Stanescu, Nkecha Hughes, Diva D De Leon, Deborah L French, Paul Gadue
Induced pluripotent stem cells were created from a pancreas agenesis patient with a mutation in GATA6. Using genome-editing technology, additional stem cell lines with mutations in both GATA6 alleles were generated and demonstrated a severe block in definitive endoderm induction, which could be rescued by re-expression of several different GATA family members. Using the endodermal progenitor stem cell culture system to bypass the developmental block at the endoderm stage, cell lines with mutations in one or both GATA6 alleles could be differentiated into β-like cells but with reduced efficiency...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28196600/genome-editing-in-hpscs-reveals-gata6-haploinsufficiency-and-a-genetic-interaction-with-gata4-in-human-pancreatic-development
#8
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/28193317/identification-of-differentially-expressed-placental-transcripts-during-multiple-gestations-in-the-eurasian-beaver-castor-fiber-l
#9
A Lipka, L Paukszto, M Majewska, J P Jastrzebski, K Myszczynski, G Panasiewicz, B Szafranska
The Eurasian beaver is one of the largest rodents that, despite its high impact on the environment, is a non-model species that lacks a reference genome. Characterising genes critical for pregnancy outcome can serve as a basis for identifying mechanisms underlying effective reproduction, which is required for the success of endangered species conservation programs. In the present study, high-throughput RNA sequencing (RNA-seq) was used to analyse global changes in the Castor fiber subplacenta transcriptome during multiple pregnancy...
February 14, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28167758/microrna-10a-is-crucial-for-endothelial-response-to-different-flow-patterns-via-interaction-of-retinoid-acid-receptors-and-histone-deacetylases
#10
Ding-Yu Lee, Ting-Er Lin, Chih-I Lee, Jing Zhou, Yi-Hsuan Huang, Pei-Ling Lee, Yu-Tsung Shih, Shu Chien, Jeng-Jiann Chiu
Histone deacetylases (HDACs) and microRNAs (miRs) have emerged as two important epigenetic factors in the regulation of vascular physiology. This study aimed to elucidate the relationship between HDACs and miRs in the hemodynamic modulation of endothelial cell (EC) dysfunction. We found that miR-10a has the lowest expression among all examined shear-responsive miRs in ECs under oscillatory shear stress (OS), and a relatively high expression under pulsatile shear stress (PS). PS and OS alter EC miR-10a expression to regulate the expression of its direct target GATA6 and downstream vascular cell adhesion molecule (VCAM)-1...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28152080/nox1-and-nox4-are-required-for-the-differentiation-of-mouse-f9-cells-into-extraembryonic-endoderm
#11
Benjamin J Dickson, Mohamed I Gatie, Danielle M Spice, Gregory M Kelly
Mouse F9 cells differentiate to primitive endoderm (PrE) when treated with retinoic acid (RA). Differentiation is accompanied by increased reactive oxygen species (ROS) levels, and while treating F9 cells with antioxidants attenuates differentiation, H2O2 treatment alone is sufficient to induce PrE. We identified the NADPH oxidase (NOX) complexes as candidates for the source of this endogenous ROS, and within this gene family, and over the course of differentiation, Nox1 and Nox 4 show the greatest upregulation induced by RA...
2017: PloS One
https://www.readbyqxmd.com/read/28103575/piwil2-transfected-human-fibroblasts-are-cancer-stem-cell-like-and-genetically-unstable
#12
Deying Zhang, Xin Wu, Xing Liu, Chunhong Cai, Guangping Zeng, Jan Rohozinski, Yuanyuan Zhang, Guanghui Wei, Dawei He
Uncontrolled cell proliferation and inhibition of apoptosis are considered to be vital for cancer initiation, maintenance, infiltration, metastasis and recurrence after anti-cancer therapy. Here we report the generation of a novel cell line by reprogramming child foreskin fibroblast with the full length apoptosis inhibitor gene PIWIL2. The fibroblasts transfected with PIWIL2 expressed the stem cell markers OCT-4, NANOG, SOX-2, KLF-4 and C-MYC; endoderm marker AFP and GATA6; mesoderm markers ACTA2 and BRACHYURY; and ectoderm markers NESTIN and TUBB3...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28102292/integrated-molecular-analysis-reveals-complex-interactions-between-genomic-and-epigenomic-alterations-in-esophageal-adenocarcinomas
#13
DunFa Peng, Yan Guo, Heidi Chen, Shilin Zhao, Kay Washington, TianLing Hu, Yu Shyr, Wael El-Rifai
The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28095922/long-noncoding-rna-braveheart-promotes-cardiogenic-differentiation-of-mesenchymal-stem-cells-in-vitro
#14
Jingying Hou, Huibao Long, Changqing Zhou, Shaoxin Zheng, Hao Wu, Tianzhu Guo, Quanhua Wu, Tingting Zhong, Tong Wang
BACKGROUND: Mesenchymal stem cells (MSCs) have limited potential of cardiogenic differentiation. In this study, we investigated the influence of long noncoding RNA Braveheart (lncRNA-Bvht) on cardiogenic differentiation of MSCs in vitro. METHODS: MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells were divided into three groups: blank control, null vector control, and lncRNA-Bvht. All three groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24 h, and 24 h of reoxygenation (20% O2)...
January 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28052061/integrated-genomic-characterization-of-oesophageal-carcinoma
#15
(no author information available yet)
Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas...
January 12, 2017: Nature
https://www.readbyqxmd.com/read/28049534/case-report-maternal-mosaicism-resulting-in-inheritance-of-a-novel-gata6-mutation-causing-pancreatic-agenesis-and-neonatal-diabetes-mellitus
#16
Daphne Yau, Elisa De Franco, Sarah E Flanagan, Sian Ellard, Miriam Blumenkrantz, John J Mitchell
BACKGROUND: Haploinsufficiency of the GATA6 transcription factor gene was recently found to be the most common cause of pancreatic agenesis, a rare cause of neonatal diabetes mellitus. Although most cases are de novo, we describe three siblings with inherited GATA6 haploinsufficiency and the rare finding of parental mosaicism. CASE PRESENTATION: The proband was born at term with severe intrauterine growth restriction, the first child of non-consanguineous parents...
January 3, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/27940555/the-csrp2bp-histone-acetyltransferase-drives-smooth-muscle-gene-expression
#17
Yanlin Ma, Qi Li, Ankang Li, Yunjian Wei, Ping Long, Xinxing Jiang, Fei Sun, Ralf Weiskirchen, Bangyong Wu, Chao Liang, Joachim Grötzinger, Yanxing Wei, Wei Yu, Mark Mercola, Yuanhua Huang, Jun Wang, Yanhong Yu, Robert J Schwartz
The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not sufficient for regulating smooth muscle cell development. It associates with other cardiovascular specific cofactors to regulate smooth muscle gene expression. Previously, we showed that the transcription co-factor CRP2 was a regulator of smooth muscle gene expression. Here, we report that CSRP2BP, a coactivator for CRP2, is a histone acetyltransferase and a driver of smooth muscle gene expression...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27929731/autophagic-homeostasis-is-required-for-the-pluripotency-of-cancer-stem-cells
#18
Tanveer Sharif, Emma Martell, Cathleen Dai, Barry E Kennedy, Patrick Murphy, Derek R Clements, Youra Kim, Patrick W K Lee, Shashi A Gujar
Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate-limiting enzyme in the NAD(+) synthesis pathway NAMPT (nicotinamide phosphoribosyltransferase) and the transcription factor POU5F1/OCT4 (POU class 5 homeobox 1)...
February 2017: Autophagy
https://www.readbyqxmd.com/read/27908934/gata6-promotes-hair-follicle-progenitor-cell-renewal-by-genome-maintenance-during-proliferation
#19
Alex B Wang, Ying V Zhang, Tudorita Tumbar
Cell proliferation is essential to rapid tissue growth and repair, but can result in replication-associated genome damage. Here, we implicate the transcription factor Gata6 in adult mouse hair follicle regeneration where it controls the renewal of rapidly proliferating epithelial (matrix) progenitors and hence the extent of production of terminally differentiated lineages. We find that Gata6 protects against DNA damage associated with proliferation, thus preventing cell cycle arrest and apoptosis. Furthermore, we show that in vivo Gata6 stimulates EDA-receptor signaling adaptor Edaradd level and NF-κB pathway activation, known to be important for DNA damage repair and stress response in general and for hair follicle growth in particular...
January 4, 2017: EMBO Journal
https://www.readbyqxmd.com/read/27902469/the-mir-196b-mirna-inhibits-the-gata6-intestinal-transcription-factor-and-is-upregulated-in-colon-cancer-patients
#20
Sebastian Fantini, Valentina Salsi, Luca Reggiani, Antonino Maiorana, Vincenzo Zappavigna
OBJECTIVE: To explore the possible misexpression of the microRNA miR-196b in colorectal cancer (CRC) and its role in controlling the expression of GATA6, a putative target gene crucial to intestinal cell homeostasis and tumorigenesis. DESIGN: The expression of miR-196b was analysed by qRT-PCR in surgical resection samples from a cohort of sporadic colon cancer patients. Manipulations of miR-196b expression were performed to demonstrate its inhibition of GATA6 protein levels...
January 17, 2017: Oncotarget
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