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https://www.readbyqxmd.com/read/28899000/rhoa-rock-signalling-is-necessary-for-lateralization-and-differentiation-of-the-developing-sinoatrial-node
#1
Rebecca Vicente-Steijn, Tim P Kelder, Leon G Tertoolen, Lambertus J Wisse, Daniël A Pijnappels, Robert E Poelmann, Martin J Schalij, Marco C deRuiter, Adriana C Gittenberger-de Groot, Monique R M Jongbloed
Aims: RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential. Later, pacemaker potential is restricted to the right-sided SAN. Disruption of RHOA expression in adult mice causes arrhythmias including bradycardia and atrial fibrillation, the mechanism of which is unknown but presumed to affect the SAN...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28894084/tbx3-dependent-amplifying-stem-cell-progeny-drives-interfollicular-epidermal-expansion-during-pregnancy-and-regeneration
#2
Ryo Ichijo, Hiroki Kobayashi, Saori Yoneda, Yui Iizuka, Hirokazu Kubo, Shigeru Matsumura, Satsuki Kitano, Hitoshi Miyachi, Tetsuya Honda, Fumiko Toyoshima
The skin surface area varies flexibly in response to body shape changes. Skin homeostasis is maintained by stem cells residing in the basal layer of the interfollicular epidermis. However, how the interfollicular epidermal stem cells response to physiological body shape changes remains elusive. Here, we identify a highly proliferative interfollicular epidermal basal cell population in the rapidly expanding abdominal skin of pregnant mice. These cells express Tbx3 that is necessary for their propagation to drive skin expansion...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28874739/dioxin-receptor-adjusts-liver-regeneration-after-acute-toxic-injury-and-protects-against-liver-carcinogenesis
#3
Nuria Moreno-Marín, Eva Barrasa, Antonio Morales-Hernández, Beroé Paniagua, Gerardo Blanco-Fernández, Jaime M Merino, Pedro M Fernández-Salguero
The aryl hydrocarbon receptor (AhR) has roles in cell proliferation, differentiation and organ homeostasis, including the liver. AhR depletion induces undifferentiation and pluripotency in normal and transformed cells. Here, AhR-null mice (AhR-/-) were used to explore whether AhR controls liver regeneration and carcinogenesis by restricting the expansion of stem-like cells and the expression of pluripotency genes. Short-term CCl4 liver damage was earlier and more efficiently repaired in AhR-/- than in AhR+/+ mice...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28859285/bovine-lineage-specification-revealed-by-single-cell-gene-expression-analysis-from-zygote-to-blastocyst
#4
Qingqing Wei, Liang Zhong, Shaopeng Zhang, Haiyuan Mu, Jinzhu Xiang, Liang Yue, Yunping Dai, Jianyong Han
Preimplantation embryos undergo zygotic genome activation and lineage specification resulting in three distinct cell types in the late blastocyst. The molecular mechanisms underlying this progress are largely unknown in bovines. Here, we sought to analyze an extensive set of regulators at the single-cell level to define the events involved in the development of the bovine blastocyst. Using a quantitative microfluidics approach in single cells, we analyzed mRNA levels of 96 genes known to function in early embryonic development and maintenance of stem cell pluripotency in parallel in 384 individual cells from bovine preimplantation embryos...
July 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28757416/the-tumour-suppressor-mir-137-inhibits-malignant-melanoma-migration-by-targetting-the-tbx3-transcription-factor
#5
Jade Peres, Eliza M Kwesi-Maliepaard, Florian Rambow, Lionel Larue, Sharon Prince
The transcription factor, TBX3, is a key driver of malignant melanoma and any drug that impacts its expression is likely to have an impact on the treatment of this highly aggressive and treatment resistant cancer. Replacement of miRNAs that target oncogenes has gained much attention as a therapy because it is anticipated to be effective with little side-effects since miRNAs are naturally occurring and often target large set of genes in the same oncogenic pathway. Here we show that miR-137 levels correlate inversely with TBX3 mRNA levels in a panel of melanoma cell lines and in a cohort of patients with primary melanoma...
July 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28751678/morpho-functional-characterization-of-the-systemic-venous-pole-of-the-reptile-heart
#6
Bjarke Jensen, Signe Vesterskov, Bastiaan J Boukens, Jan M Nielsen, Antoon F M Moorman, Vincent M Christoffels, Tobias Wang
Mammals evolved from reptile-like ancestors, and while the mammalian heart is driven by a distinct sinus node, a sinus node is not apparent in reptiles. We characterized the myocardial systemic venous pole, the sinus venosus, in reptiles to identify the dominant pacemaker and to assess whether the sinus venosus remodels and adopts an atrium-like phenotype as observed in mammals. Anolis lizards had an extensive sinus venosus of myocardium expressing Tbx18. A small sub-population of cells encircling the sinuatrial junction expressed Isl1, Bmp2, Tbx3, and Hcn4, homologues of genes marking the mammalian sinus node...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28674041/transient-notch-activation-induces-long-term-gene-expression-changes-leading-to-sick-sinus-syndrome-in-mice
#7
Yun Qiao, Catherine Lipovsky, Stephanie Hicks, Somya Bhatnagar, Gang Li, Aditi Khandekar, Robert Guzy, Kel Vin Woo, Colin G Nichols, Igor R Efimov, Stacey Rentschler
RATIONALE: Notch signaling programs cardiac conduction during development, and in the adult ventricle, injury-induced Notch reactivation initiates global transcriptional and epigenetic changes. OBJECTIVE: To determine whether Notch reactivation may stably alter atrial ion channel gene expression and arrhythmia inducibility. METHODS AND RESULTS: To model an injury response and determine the effects of Notch signaling on atrial electrophysiology, we transiently activate Notch signaling within adult myocardium using a doxycycline-inducible genetic system (inducible Notch intracellular domain [iNICD])...
August 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28579578/the-t-box-transcription-factor-3-in-development-and-cancer
#8
Tarryn Willmer, Aretha Cooper, Jade Peres, Rehana Omar, Sharon Prince
T-box factors comprise an archaic family of evolutionary conserved transcription factors that regulate patterns of gene expression essential for embryonic development. The T-box transcription factor 3 (TBX3), a member of this family, is expressed in several tissues and plays critical roles in, among other structures, the heart, mammary gland and limbs and haploinsufficiency of the human TBX3 gene is the genetic basis for the autosomal dominant disorder, ulnar-mammary syndrome. Overexpression of TBX3 on the other hand has been linked to several cancers including melanoma, breast, pancreatic, liver, lung, head and neck, ovarian, bladder carcinomas and a number of sarcoma subtypes...
June 4, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28553934/phenotypic-screening-identifies-axl-kinase-as-a-negative-regulator-of-an-alveolar-epithelial-cell-phenotype
#9
Naoya Fujino, Hiroshi Kubo, Rose A Maciewicz
Loss of epithelial barrier integrity is implicated in a number of human lung diseases. However, the molecular pathways underlying this process are poorly understood. In a phenotypic screen, we identified Axl kinase as a negative regulator of epithelial phenotype and function. Furthermore, suppression of Axl activity by a small molecule kinase inhibitor or downregulation of Axl expression by small interfering RNA led to: (1) the increase in epithelial surfactant protein expression; (2) a cell morphology transition from front-rear polarity to cuboidal shape; (3) the cytoskeletal re-organization resulting in decreased cell mobility; and (4) the acquisition of epithelial junctions...
September 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28521440/t-box-3-overexpression-is-associated-with-poor-prognosis-of-non-small-cell-lung-cancer
#10
Yueming Wu, Jiang Feng, Weiwei Hu, Yawei Zhang
T-box 3 (Tbx3), a member of the T-box transcription factor family, serves a crucial role in embryonic development and cancer progression. Previous studies have demonstrated the clinical significance of Tbx3 in numerous types of cancer. However, the expression level and pathological function of Tbx3 in non-small cell lung cancer (NSCLC) are unknown. To the best of our knowledge, the present study provided the first evidence demonstrating the clinicopathological significance of Tbx3 in NSCLC. Tbx3 was revealed to be overexpressed in NSCLC cell lines and tissues obtained from patients with NSCLC by reverse transcription-quantitative polymerase chain reaction and western blot analysis...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28466692/dna-methylation-changes-in-tbx3-in-a-mouse-model-exposed-to-polybrominated-diphenyl-ethers
#11
Takashi Shimbo, June K Dunnick, Amy Brix, Deepak Mav, Ruchir Shah, John D Roberts, Paul A Wade
DE-71, a commercial mixture of polybrominated diphenyl ethers widely used in flame retardants, is a pervasive environmental contaminant due to its continuing release from waste material and its long half-life in humans. Although the genotoxic potential of DE-71 appears to be low based on bacterial mutagenicity, it remains a public health concern due to its reported involvement in tumor development. Molecular mechanisms by which DE-71 influences tumor incidence or progression remain understudied. We used liver carcinoma tissue from mice exposed to DE-71 to test the hypothesis that epigenetic alterations consistent with tumor development, specifically DNA methylation, result from long-term DE-71 exposure...
May 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28432217/rar%C3%AE-2-is-required-for-vertebrate-somitogenesis
#12
Amanda Janesick, Weiyi Tang, Tuyen T L Nguyen, Bruce Blumberg
During vertebrate somitogenesis, retinoic acid is known to establish the position of the determination wavefront, controlling where new somites are permitted to form along the anteroposterior body axis. Less is understood about how RAR regulates somite patterning, rostral-caudal boundary setting, specialization of myotome subdivisions, or the specific RAR subtype that is required for somite patterning. Characterizing the function of RARβ has been challenging due to the absence of embryonic phenotypes in murine loss-of-function studies...
April 21, 2017: Development
https://www.readbyqxmd.com/read/28392218/promyelocytic-leukemia-protein-is-an-essential-regulator-of-stem-cell-pluripotency-and-somatic-cell-reprogramming
#13
Christiana Hadjimichael, Konstantina Chanoumidou, Christoforos Nikolaou, Antonios Klonizakis, Gesthimani-Ioanna Theodosi, Takis Makatounakis, Joseph Papamatheakis, Androniki Kretsovali
Promyelocytic leukemia protein (PML), the main constituent of PML nuclear bodies, regulates various physiological processes in different cell types. However, little is known about its functions in embryonic stem cells (ESC). Here, we report that PML contributes to ESC self-renewal maintenance by controlling cell-cycle progression and sustaining the expression of crucial pluripotency factors. Transcriptomic analysis and gain- or loss-of-function approaches showed that PML-deficient ESC exhibit morphological, metabolic, and growth properties distinct to naive and closer to the primed pluripotent state...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28382491/tbx18-dependent-differentiation-of-brown-adipose-tissue-derived-stem-cells-toward-cardiac-pacemaker-cells
#14
Lei Chen, Zi-Jun Deng, Jian-Sheng Zhou, Rui-Juan Ji, Xi Zhang, Chuan-Sen Zhang, Yu-Quan Li, Xiang-Qun Yang
A cell-sourced biological pacemaker is a promising therapeutic approach for sick sinus syndrome (SSS) or severe atrial ventricular block (AVB). Adipose tissue-derived stem cells (ATSCs), which are optimal candidate cells for possible use in regenerative therapy for acute or chronic myocardial injury, have the potential to differentiate into spontaneous beating cardiomyocytes. However, the pacemaker characteristics of the beating cells need to be confirmed, and little is known about the underlying differential mechanism...
April 5, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28351298/aberrant-gene-specific-dna-methylation-signature-analysis-in-cervical-cancer
#15
Samatha Bhat, Shama Prasada Kabekkodu, Vinay Koshy Varghese, Sanjiban Chakrabarty, Sandeep P Mallya, Harish Rotti, Deeksha Pandey, Pralhad Kushtagi, Kapaettu Satyamoorthy
Multicomponent molecular modifications such as DNA methylation may offer sensitive and specific cervical intraepithelial neoplasia and cervical cancer biomarkers. In this study, we tested cervical tissues at various stages of tumor progression for 5-methylcytosine and 5-hydroxymethylcytosine levels and also DNA promoter methylation profile of a panel of genes for its diagnostic potential. In total, 5-methylcytosine, 5-hydroxymethylcytosine, and promoter methylation of 33 genes were evaluated by reversed-phase high-performance liquid chromatography, enzyme-linked immunosorbent assay based technique, and bisulfate-based next generation sequencing...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28298436/the-chromatin-remodeler-chd4-maintains-embryonic-stem-cell-identity-by-controlling-pluripotency-and-differentiation-associated-genes
#16
Haixin Zhao, Zhijun Han, Xinyuan Liu, Junjie Gu, Fan Tang, Gang Wei, Ying Jin
The unique properties of embryonic stem cells (ESCs), including unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of transcriptional factors and epigenetic modulators. However, the molecular mechanisms underlying the function of these regulators are not fully elucidated. Chromodomain helicase DNA-binding protein 4 (Chd4), an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28238063/functional-germline-variants-in-driver-genes-of-breast-cancer
#17
Stella Göhler, Miguel Inacio Da Silva Filho, Robert Johansson, Kerstin Enquist-Olsson, Roger Henriksson, Kari Hemminki, Per Lenner, Asta Försti
PURPOSE: Germline mutations in tumour suppressor genes cause various cancers. These genes are also somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic breast tumours. METHODS: After excluding the well-characterized breast cancer (BC) genes, we screened 15 novel genes consistently classified as BC driver genes in next-generation sequencing approaches for single nucleotide polymorphisms (SNPs)...
April 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#18
E Zacksenhaus, J C Liu, Z Jiang, Y Yao, L Xia, M Shrestha, Y Ben-David
Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28205312/essential-roles-of-tbx3-in-embryonic-skin-development-during-epidermal-stratification
#19
Ryo Ichijo, Yui Iizuka, Hirokazu Kubo, Fumiko Toyoshima
Stepwise differentiation of epidermal cells is essential for development of stratified epithelium, but the underlying mechanisms remain unclear. Here, we show that Tbx3, a member of the T-box family of transcription factors, plays a pivotal role in this mechanism. Tbx3 is expressed in both basal and suprabasal cells in the interfollicular epidermis of mouse embryos. Epidermis-specific Tbx3 conditional knockout (cKO) embryos are small in size and display a thinner epidermis with an impaired barrier function...
March 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28169326/novel-peptides-for-deciphering-structural-and-signalling-functions-of-e-cadherin-in-mouse-embryonic-stem-cells
#20
Joe M Segal, Christopher M Ward
We have previously shown that E-cadherin regulates the naive pluripotent state of mouse embryonic stem cells (mESCs) by enabling LIF-dependent STAT3 phosphorylation, with E-cadherin null mESCs exhibiting over 3000 gene transcript alterations and a switch to Activin/Nodal-dependent pluripotency. However, elucidation of the exact mechanisms associated with E-cadherin function in mESCs is compounded by the difficulty in delineating the structural and signalling functions of this protein. Here we show that mESCs treated with the E-cadherin neutralising antibody DECMA-1 or the E-cadherin binding peptide H-SWELYYPLRANL-NH2 (Epep) exhibit discrete profiles for pluripotent transcripts and NANOG protein expression, demonstrating that the type of E-cadherin inhibitor employed dictates the cellular phenotype of mESCs...
February 7, 2017: Scientific Reports
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