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https://www.readbyqxmd.com/read/29229250/genome-wide-transcriptomics-analysis-identifies-sox7-and-sox18-as-specifically-regulated-by-gata4-in-cardiomyogenesis
#1
Boni A Afouda, Adam T Lynch, Eduardo de Paiva Alves, Stefan Hoppler
The transcription factors GATA4, GATA5 and GATA6 are important regulators of heart muscle differentiation (cardiomyogenesis), which function in a partially redundant manner. We identified genes specifically regulated by individual cardiogenic GATA factors in a genome-wide transcriptomics analysis. The genes regulated by gata4 are particularly interesting because GATA4 is able to induce differentiation of beating cardiomyocytes in Xenopus and in mammalian systems. Among the specifically gata4-regulated transcripts we identified two SoxF family members, sox7 and sox18...
December 8, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29216542/loss-of-heme-oxygenase-1-accelerates-mesodermal-gene-expressions-during-embryoid-body-development-from-mouse-embryonic-stem-cells
#2
Yan-Liang Lai, Chen-Yu Lin, Wei-Cheng Jiang, Yen-Chun Ho, Chung-Huang Chen, Shaw-Fang Yet
Heme oxygenase (HO)-1 is an inducible stress response protein and well known to protect cells and tissues against injury. Despite its important function in cytoprotection against physiological stress, the role of HO-1 in embryonic stem cell (ESC) differentiation remains largely unknown. We showed previously that induced pluripotent stem (iPS) cells that lack HO-1 are more sensitive to oxidant stress-induced cell death and more prone to lose pluripotent markers upon LIF withdrawal. To elucidate the role of HO-1 in ESC differentiation and to rule out the controversy of potential gene flaws in iPS cells, we derived and established mouse HO-1 knockout ESC lines from HO-1 knockout blastocysts...
November 22, 2017: Redox Biology
https://www.readbyqxmd.com/read/29197504/gata6-restricts-isl1-to-the-posterior-of-nascent-hindlimb-buds-through-isl1-cis-regulatory-modules
#3
Naoyuki Tahara, Ryutaro Akiyama, Joshua W M Theisen, Hiroko Kawakami, Julia Wong, Daniel J Garry, Yasuhiko Kawakami
Isl1 is required for two processes during hindlimb development: initiation of the processes directing hindlimb development in the lateral plate mesoderm and configuring posterior hindlimb field in the nascent hindlimb buds. During these processes, Isl1 expression is restricted to the posterior mesenchyme of hindlimb buds. How this dynamic change in Isl1 expression is regulated remains unknown. We found that two evolutionarily conserved sequences, located 3' to the Isl1 gene, regulate LacZ transgene expression in the hindlimb-forming region in mouse embryos...
November 29, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29174091/pancreatic-hemi-agenesis-in-men1-a-clinical-report
#4
Wouter J Vinck, Frank Van de Mierop, François Van Mieghem, Maarten Vinck, Herman Becq, Geneviève Michils
We first describe a patient with multiple endocrine neoplasia type 1 (MEN1) and dorsal pancreatic hemi-agenesis. Previously, pancreas divisum has been reported in MEN1. Recent data in mice have elucidated the molecular mechanisms of pancreatic endoderm specification. Disinhibition of hedgehog signaling appears to be important in how Gata4 and Gata6 variants cause pancreatic agenesis. Disinhibition of hedgehog signaling has also been observed in Men1 knockout pancreatic islets. Although we cannot exclude a spurious association between dorsal pancreatic hemi-agenesis and MEN1 in our patient, we argue that developmental abnormalities of the pancreas may have to be considered as possibly related to the MEN1 phenotype...
November 22, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29143549/negative-impact-of-hyperglycaemia-on-mouse-alveolar-development
#5
Mei-Yao He, Guang Wang, Sha-Sha Han, Ke Li, Ya Jin, Meng Liu, Zhen-Peng Si, Ju Wang, Guo-Sheng Liu, Xuesong Yang
Diabetes mellitus in pregnancy has been known to affect the embryonic development of various systems, including cardiovascular and nervous systems. However, whether this disease could have a negative impact on embryonic respiratory system remains controversial. In this study, we demonstrated that pregestational diabetes mellitus (PGDM)-induced defects in lung development in mice are mainly characterized by the changes in the morphological structure of the lung. Immunostaining and Western blotting showed that proliferation increased and apoptosis decreased in PGDM...
November 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29133875/heart-function-and-thoracic-aorta-gene-expression-profiling-studies-of-ginseng-combined-with-different-herbal-medicines-in-enos-knockout-mice
#6
Yuchen Qian, Pan Li, Bin Lv, Xiaoqing Jiang, Ting Wang, Han Zhang, Xiaoying Wang, Xiumei Gao
Ginseng, a popular herbal remedy, is often used in combination with other drugs to achieve the maximum therapeutic response. Shenfu (SFI) and Shenmai injection (SMI) have been widely used to treat cardiovascular disease in China. Our study explored the cardiovascular protection of SFI and SMI in eNOS knockout mice to investigate the differences and similarities of the two ginseng-combinations. Transthoracic echocardiography was performed to evaluate the left ventricular structure and function at baseline and 3, 7, and 14 days after drug administration...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29119099/wnt-and-hedgehog-signaling-regulate-the-differentiation-of-f9-cells-into-extraembryonic-endoderm
#7
Gurjoth S J Deol, Tina N Cuthbert, Mohamed I Gatie, Danielle M Spice, Lindsay R Hilton, Gregory M Kelly
Mouse F9 cells differentiate into primitive extraembryonic endoderm (PrE) when treated with retinoic acid (RA), and this is accompanied by an up-regulation of Gata6. The role of the GATA6 network in PrE differentiation is known, and we have shown it directly activates Wnt6. Canonical Wnt/β-catenin signaling is required by F9 cells to differentiate to PrE, and this, like most developmental processes, requires input from one or more additional pathways. We found both RA and Gata6 overexpression, can induce the expression of Indian Hedgehog (Ihh) and a subset of its target genes through Gli activation during PrE induction...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29106391/aberrant-gata2-epigenetic-dysregulation-induces-a-gata2-gata6-switch-in-human-gastric-cancer
#8
S H Song, M S Jeon, J W Nam, J K Kang, Y J Lee, J Y Kang, H P Kim, S W Han, G H Kang, T Y Kim
Six GATA transcription factors play important roles in eukaryotic development. Among these, GATA2, an essential factor for the hematopoietic cell lineage, exhibits low expression in human gastric tissues, whereas GATA6, which is crucial for gastrointestinal development and differentiation, is frequently amplified and/or overexpressed in human gastric cancer. Interestingly, we found that GATA6 was overexpressed in human gastric cancer cells only when GATA2 expression was completely absent, thereby showing an inverse correlation between GATA2 and GATA6...
November 6, 2017: Oncogene
https://www.readbyqxmd.com/read/29101065/targeted-sequencing-identifies-novel-gata6-variants-in-a-large-cohort-of-patients-with-conotruncal-heart-defects
#9
Erge Zhang, Nanchao Hong, Sun Chen, Qihua Fu, Fen Li, Yu Yu, Kun Sun
Studies have highlighted the critical role of GATA6 in conotruncal heart defects (CTDs). Nevertheless, relationship between GATA6 variants and different CTDs remains largely unknown. Here GATA6 gene was screened in 542 patients with CTDs using targeted sequencing. Variant frequency was 2.0% (11/542). Three novel variants: c.86C>A (p.A29E), c.296T>A (p.V99D) and c.1254delC (p.S418fs) were identified in patients with transposition of the great arteries, double outlet right ventricle and persistent truncus arteriosus, respectively, but in none of the 400 controls...
October 31, 2017: Gene
https://www.readbyqxmd.com/read/29038332/gata-transcription-factors-in-testicular-adrenal-rest-tumours
#10
Manon Engels, Paul N Span, Rod T Mitchell, Joop J T M Heuvel, Monica A Marijnissen-van Zanten, Antonius E van Herwaarden, Christina A Hulsbergen-van de Kaa, Egbert Oosterwijk, Nike M Stikkelbroeck, Lee B Smith, Fred C G J Sweep, Hedi L Claahsen-van der Grinten
Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8))...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29035371/lncrna-mir100hg-derived-mir-100-and-mir-125b-mediate-cetuximab-resistance-via-wnt-%C3%AE-catenin-signaling
#11
Yuanyuan Lu, Xiaodi Zhao, Qi Liu, Cunxi Li, Ramona Graves-Deal, Zheng Cao, Bhuminder Singh, Jeffrey L Franklin, Jing Wang, Huaying Hu, Tianying Wei, Mingli Yang, Timothy J Yeatman, Ethan Lee, Kenyi Saito-Diaz, Scott Hinger, James G Patton, Christine H Chung, Stephan Emmrich, Jan-Henning Klusmann, Daiming Fan, Robert J Coffey
De novo and acquired resistance, which are largely attributed to genetic alterations, are barriers to effective anti-epidermal-growth-factor-receptor (EGFR) therapy. To generate cetuximab-resistant cells, we exposed cetuximab-sensitive colorectal cancer cells to cetuximab in three-dimensional culture. Using whole-exome sequencing and transcriptional profiling, we found that the long non-coding RNA MIR100HG and two embedded microRNAs, miR-100 and miR-125b, were overexpressed in the absence of known genetic events linked to cetuximab resistance...
November 2017: Nature Medicine
https://www.readbyqxmd.com/read/28977863/clinical-roles-of-the-aberrantly-expressed-lncrnas-in-lung-squamous-cell-carcinoma-a-study-based-on-rna-sequencing-and-microarray-data-mining
#12
Wen-Jie Chen, Rui-Xue Tang, Rong-Quan He, Dong-Yao Li, Liang Liang, Jiang-Hui Zeng, Xiao-Hua Hu, Jie Ma, Shi-Kang Li, Gang Chen
Lung squamous cell carcinoma (LUSC) accounts for a significant proportion of lung cancer and there have been few therapeutic alternatives for recurrent LUSC due to the lack of specific driver molecules. To investigate the prospective role of lncRNAs in the tumorigenesis and progression of LUSC, the aberrantly expressed lncRNAs were calculated based on The Cancer Genome Atlas RNA-seq data. Of 7589 lncRNAs with 504 LUSC cases, 884 lncRNAs were identified as being aberrantly expressed (|log2 fold change| >2 and adjusted P<0...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975155/genome-wide-scan-in-hispanics-highlights-candidate-loci-for-brain-white-matter-hyperintensities
#13
Ashley Beecham, Chuanhui Dong, Clinton B Wright, Nicole Dueker, Adam M Brickman, Liyong Wang, Charles DeCarli, Susan H Blanton, Tatjana Rundek, Richard Mayeux, Ralph L Sacco
OBJECTIVE: To investigate genetic variants influencing white matter hyperintensities (WMHs) in the understudied Hispanic population. METHODS: Using 6.8 million single nucleotide polymorphisms (SNPs), we conducted a genome-wide association study (GWAS) to identify SNPs associated with WMH volume (WMHV) in 922 Hispanics who underwent brain MRI as a cross-section of 2 community-based cohorts in the Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project...
October 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28952437/a-tissue-specific-gata6-driven-transcriptional-program-instructs-remodeling-of-the-mature-arterial-tree
#14
Marta Losa, Victor Latorre, Munazah Andrabi, Franck Ladam, Charles Sagerström, Ana Novoa, Peyman Zarrineh, Laure Bridoux, Neil A Hanley, Moises Mallo, Nicoletta Bobola
Connection of the heart to the systemic circulation is a critical developmental event that requires selective preservation of embryonic vessels (aortic arches). However, why some aortic arches regress while others are incorporated into the mature aortic tree remains unclear. By microdissection and deep sequencing in mouse, we find that neural crest (NC) only differentiates into vascular smooth muscle cells (SMCs) around those aortic arches destined for survival and reorganization, and identify the transcription factor Gata6 as a crucial regulator of this process...
September 27, 2017: ELife
https://www.readbyqxmd.com/read/28943339/%C3%AE-catenin-coordinates-with-jup-and-the-tcf1-gata6-axis-to-regulate-human-embryonic-stem-cell-fate
#15
Hongwei Sun, Xiaohu Wang, Kuisheng Liu, Mengmeng Guo, Yan Zhang, Qi-Long Ying, Shoudong Ye
β-catenin-mediated signaling has been extensively studied in regard to its role in the regulation of human embryonic stem cells (hESCs). However, the results are controversial and the mechanism by which β-catenin regulates the hESC fate remains unclear. Here, we report that β-catenin and γ-catenin are functionally redundant in mediating hESC adhesion and are required for embryoid body formation, but both genes are dispensable for hESC maintenance, as the undifferentiated state of β-catenin and γ-catenin double deficient hESCs can be maintained...
November 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28943029/generation-of-mouse-and-human-organoid-forming-intestinal-progenitor-cells-by-direct-lineage-reprogramming
#16
Shizuka Miura, Atsushi Suzuki
Intestinal organoids hold great promise as a valuable tool for studying and treating intestinal diseases. The currently available sources of human intestinal organoids, tissue fragments or pluripotent stem cells, involve invasive procedures or complex differentiation protocols, respectively. Here, we show that a set of four transcription factors, Hnf4α, Foxa3, Gata6, and Cdx2, can directly reprogram mouse fibroblasts to acquire the identity of fetal intestine-derived progenitor cells (FIPCs). These induced FIPCs (iFIPCs) form spherical organoids that develop into adult-type budding organoids containing cells with intestinal stem cell properties...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28938416/pancreatic-histopathology-of-human-monogenic-diabetes-due-to-causal-variants-in-kcnj11-hnf1a-gata6-and-lmna
#17
May Sanyoura, Laura Jacobsen, David Carmody, Daniela Del Gaudio, Gorka Alkorta-Aranburu, Kelly Arndt, Ying Ying Hu, Frances Kobiernicki, Irina Kusmartseva, Mark A Atkinson, Louis H Philipson, Desmond Schatz, Martha Campbell-Thompson, Siri Atma W Greeley
Context: Monogenic diabetes is thought to account for 2% of all diabetes cases but most patients are misdiagnosed as type 1 or type 2 diabetes. To date, little is known about the histopathological features of pancreases from patients with monogenic diabetes. Objective: Retrospective study of the JDRF Network for Pancreatic Organ donors with Diabetes biorepository was used to identify possible cases with monogenic diabetes and to compare effects of genetic variants on pancreas histology...
August 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28935706/suppression-of-erk-signalling-abolishes-primitive-endoderm-formation-but-does-not-promote-pluripotency-in-rabbit-embryo
#18
Anna Piliszek, Zofia E Madeja, Berenika Plusa
Formation of epiblast (EPI) - the founder line of all embryonic lineages - and extra-embryonic supportive tissues is one of the key events in mammalian development. The prevailing model of early mammalian development is based almost exclusively on the mouse. Here, we provide a comprehensive, stage-by-stage analysis of EPI and extra-embryonic primitive endoderm (PrE) formation during preimplantation development of the rabbit. Although we observed that rabbit embryos have several features in common with mouse embryos, including a stage-related initiation of lineage specification, our results demonstrate the existence of some key differences in lineage specification among mammals...
October 15, 2017: Development
https://www.readbyqxmd.com/read/28877476/mtorc2-signaling-selectively-regulates-the-generation-and-function-of-tissue-resident-peritoneal-macrophages
#19
Min-Hee Oh, Samuel L Collins, Im-Hong Sun, Ada J Tam, Chirag H Patel, Matthew L Arwood, Yee Chan-Li, Jonathan D Powell, Maureen R Horton
Tissue-resident macrophages play critical roles in sentinel and homeostatic functions as well as in promoting inflammation and immunity. It has become clear that the generation of these cells is highly dependent upon tissue-specific cues derived from the microenvironment that, in turn, regulate unique differentiation programs. Recently, a role for GATA6 has emerged in the differentiation programming of resident peritoneal macrophages. We identify a critical role for mTOR in integrating cues from the tissue microenvironment in regulating differentiation and metabolic reprogramming...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28870993/klf5-maintains-the-balance-of-primitive-endoderm-versus-epiblast-specification-during-mouse-embryonic-development-by-suppression-of-fgf4
#20
Takuya Azami, Tsuyoshi Waku, Ken Matsumoto, Hyojung Jeon, Masafumi Muratani, Akihiro Kawashima, Jun Yanagisawa, Ichiro Manabe, Ryozo Nagai, Tilo Kunath, Tomonori Nakamura, Kazuki Kurimoto, Mitinori Saitou, Satoru Takahashi, Masatsugu Ema
The inner cell mass of the mouse blastocyst gives rise to the pluripotent epiblast (EPI), which forms the embryo proper, and the primitive endoderm (PrE), which forms extra-embryonic yolk sac tissues. All inner cells coexpress lineage markers such as Nanog and Gata6 at embryonic day (E) 3.25, and the EPI and PrE precursor cells eventually segregate to exclusively express Nanog and Gata6, respectively. Fibroblast growth factor (FGF)-extracellular signal-regulated kinase (ERK) signalling is involved in segregation of the EPI and PrE lineages; however, the mechanism involved in Fgf4 regulation is poorly understood...
October 15, 2017: Development
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