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https://www.readbyqxmd.com/read/28198062/curcumin-suppresses-lung-cancer-stem-cells-via-inhibiting-wnt-%C3%AE-catenin-and-sonic-hedgehog-pathways
#1
Jian-Yun Zhu, Xue Yang, Yue Chen, Ye Jiang, Shi-Jia Wang, Yuan Li, Xiao-Qian Wang, Yu Meng, Ming-Ming Zhu, Xiao Ma, Cong Huang, Rui Wu, Chun-Feng Xie, Xiao-Ting Li, Shan-Shan Geng, Jie-Shu Wu, Cai-Yun Zhong, Hong-Yu Han
Cancer stem cells (CSCs) are highly implicated in the progression of human cancers. Thus, targeting CSCs may be a promising strategy for cancer therapy. Wnt/β-catenin and Sonic Hedgehog pathways play an important regulatory role in maintaining CSC characteristics. Natural compounds, such as curcumin, possess chemopreventive properties. However, the interventional effect of curcumin on lung CSCs has not been clarified. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells...
February 15, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28193206/inducing-goat-pluripotent-stem-cells-with-four-transcription-factor-mrnas-that-activate-endogenous-promoters
#2
Hao Chen, Qisheng Zuo, Yingjie Wang, Jiuzhou Song, Huilin Yang, Yani Zhang, Bichun Li
BACKGROUND: Traditional approaches for generating goat pluripotent stem cells (iPSCs) suffer from complexity and low preparation efficiency. Therefore, we tried to derive goat iPSCs with a new method by transfecting exogenous Oct4, Sox2, Klf4 and c-Myc mRNAs into goat embryonic fibroblasts (GEFs), and explore the mechanisms regarding the transcription regulation of the reprogramming factors in goat iPSCs induction. RESULTS: mRNAs of the four reprogramming factors were transfected into GEFs, and were localized in nucleus with approximately 90% transfection efficiency...
February 13, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28192421/g1-cyclins-link-proliferation-pluripotency-and-differentiation-of-embryonic-stem-cells
#3
Lijun Liu, Wojciech Michowski, Hiroyuki Inuzuka, Kouhei Shimizu, Naoe Taira Nihira, Joel M Chick, Na Li, Yan Geng, Alice Y Meng, Alban Ordureau, Aleksandra Kołodziejczyk, Keith L Ligon, Roderick T Bronson, Kornelia Polyak, J Wade Harper, Steven P Gygi, Wenyi Wei, Piotr Sicinski
Progression of mammalian cells through the G1 and S phases of the cell cycle is driven by the D-type and E-type cyclins. According to the current models, at least one of these cyclin families must be present to allow cell proliferation. Here, we show that several cell types can proliferate in the absence of all G1 cyclins. However, following ablation of G1 cyclins, embryonic stem (ES) cells attenuated their pluripotent characteristics, with the majority of cells acquiring the trophectodermal cell fate. We established that G1 cyclins, together with their associated cyclin-dependent kinases (CDKs), phosphorylate and stabilize the core pluripotency factors Nanog, Sox2 and Oct4...
February 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28188976/influence-of-hypoxia-on-the-stemness-of-umbilical-cord-matrix-derived-mesenchymal-stem-cells-cultured-on-chitosan-films
#4
Takashi Taguchi, Jane Y Cho, Jijun Hao, Yvette S Nout-Lomas, Kyung-Sun Kang, Dominique J Griffon
Chitosan is attractive as a substrate for stem cell expansion because it improves stemness through formation of spheroids. Hypoxia has also been proposed as a strategy to enhance stemness and survival of stem cells after in vivo implantation. This study was therefore designed to evaluate the influence of hypoxia on chitosan-induced behavior of stem cells. Umbilical cord matrix-derived stem cells were cultured on chitosan film or standard plate under normoxia and hypoxia, for 3 and 7 days. Based on immunophenotyping, chitosan strongly suppresses the expression of CD90 and CD105 cell surface markers, changes partially reversed by combined exposure to hypoxia...
February 11, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28186969/high-oct4a-levels-drive-tumorigenicity-and-metastatic-potential-of-medulloblastoma-cells
#5
Patrícia Benites Gonçalves da Silva, Márcia Cristina Teixeira Dos Santos, Carolina Oliveira Rodini, Carolini Kaid, Márcia Cristina Leite Pereira, Gabriela Furukawa, Daniel Sanzio Gimenes da Cruz, Mauricio Barbugiani Goldfeder, Clarissa Ribeiro Reily Rocha, Carla Rosenberg, Oswaldo Keith Okamoto
Medulloblastoma is a highly aggressive pediatric brain tumor, in which sporadic expression of the pluripotency factor OCT4 has been recently correlated with poor patient survival. However the contribution of specific OCT4 isoforms to tumor aggressiveness is still poorly understood. Here, we report that medulloblastoma cells stably overexpressing the OCT4A isoform displayed enhanced clonogenic, tumorsphere generation, and invasion capabilities. Moreover, in an orthotopic metastatic model of medulloblastoma, OCT4A overexpressing cells generated more developed, aggressive and infiltrative tumors, with tumor-bearing mice attaining advanced metastatic disease and shorter survival rates...
7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185954/wip1-directly-dephosphorylates-nlk-and-increases-wnt-activity-during-germ-cell-development
#6
Seung-Ju Cho, Bok-Sik Cha, Ok-Seon Kwon, Jisun Lim, Dong-Myung Shin, Dong Wook Han, Tohru Ishitani, Eek-Hoon Jho, Albert J Fornace, Hyuk-Jin Cha
Mice null for wild-type p53-induced phosphatase 1 (WIP1) display defects in testis development and spermatogenesis, resulting in reduced fertility. However, the molecular mechanism underlying these abnormalities in the testis remains uncharacterized. We report that the phosphatase activity of WIP1 increases Wnt activity through Nemo-like kinase (NLK). WIP1 directly interacted with NLK, which is highly homologous to p38 MAPK, a WIP1 substrate, and dephosphorylated its activation site. The WIP1-mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer-binding factor 1 (LEF1), disrupting its interaction with β-catenin...
February 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28170296/muse-cells-derived-from-dermal-tissues-can-differentiate-into-melanocytes
#7
Ting Tian, Ru-Zhi Zhang, Yu-Hua Yang, Qi Liu, Di Li, Xiao-Ru Pan
The objective of the authors has been to obtain multilineage-differentiating stress-enduring cells (Muse cells) from primary cultures of dermal fibroblasts, identify their pluripotency, and detect their ability to differentiate into melanocytes. The distribution of SSEA-3-positive cells in human scalp skin was assessed by immunohistochemistry, and the distribution of Oct4, Sox2, Nanog, and SSEA-3-positive cells was determined by immunofluorescence staining. The expression levels of Sox2, Oct4, hKlf4, and Nanog mRNAs and proteins in Muse cells were determined by reverse transcription polymerase chain reaction (RT-PCR) analyses and Western blots, respectively...
February 7, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28166455/structural-and-mechanistic-insights-into-nuclear-transport-and-delivery-of-the-critical-pluripotency-factor-oct4-to-dna
#8
Takahide Okuyama, Ryosuke Yamagishi, Jiro Shimada, Masaaki Ikeda, Yayoi Maruoka, Hiroki Kaneko
Oct4 is a master regulator of the induction and maintenance of cellular pluripotency, and has crucial roles in early stages of differentiation. It is the only factor that cannot be substituted by other members of the same protein family to induce pluripotency. However, although Oct4 nuclear transport and delivery to target DNA are critical events for reprogramming to pluripotency, little is known about the molecular mechanism. Oct4 is imported to the nucleus by the classical nuclear transport mechanism, which requires importin α as an adaptor to bind the nuclear localization signal (NLS)...
February 6, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28166426/the-elusive-role-of-mitotic-bookmarking-in-transcriptional-regulation-insights-from-sox2
#9
Cédric Deluz, Daniel Strebinger, Elias T Friman, David M Suter
The ability of some transcription factors to remain bound to specific genes on condensed mitotic chromosomes has been suggested to play a role in their rapid transcriptional reactivation upon mitotic exit. We have recently shown that SOX2 and OCT4 remain associated to mitotic chromosomes, and that depletion of SOX2 at the mitosis-G1 (M-G1) transition impairs its ability to maintain pluripotency and drive neuroectodermal commitment. Here we report on the role of SOX2 at the M-G1 transition in regulating transcriptional activity of embryonic stem cells...
February 6, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28165055/human-embryonic-and-induced-pluripotent-stem-cells-maintain-phenotype-but-alter-their-metabolism-after-exposure-to-rock-inhibitor
#10
Spyros I Vernardis, Konstantinos Terzoudis, Nicki Panoskaltsis, Athanasios Mantalaris
Human pluripotent stem cells (hPSCs) are adhesion-dependent cells that require cultivation in colonies to maintain growth and pluripotency. Robust differentiation protocols necessitate single cell cultures that are achieved by use of ROCK (Rho kinase) inhibitors. ROCK inhibition enables maintenance of stem cell phenotype; its effects on metabolism are unknown. hPSCs were exposed to 10 μM ROCK inhibitor for varying exposure times. Pluripotency (TRA-1-81, SSEA3, OCT4, NANOG, SOX2) remained unaffected, until after prolonged exposure (96 hrs)...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28162122/analysis-of-cyclin-e1-functions-in-porcine-preimplantation-embryonic-development-by-fluorescence-microscopy
#11
Jing Guo, Kyung-Tae Shin, Xiang-Shun Cui
Cyclin E1 (CCNE1) is a core component of cell cycle regulation that drives the transition into the S phase. CCNE1 plays critical roles in cell cycle, cell proliferation, and cellular functions. However, the function of CCNE1 in early embryonic development is limited. In the present study, the function and expression of Ccne1 in porcine early parthenotes were examined. Immunostaining experiments showed that CCNE1 localized in the nucleus, starting at the four-cell stage. Knockdown of Ccne1 by double-stranded RNA resulted in the failure of blastocyst formation and induced blastocyst apoptosis...
February 6, 2017: Microscopy and Microanalysis
https://www.readbyqxmd.com/read/28157483/distinct-enhancer-activity-of-oct4-in-naive-and-primed-mouse-pluripotency
#12
Hyun Woo Choi, Jin Young Joo, Yean Ju Hong, Jong Soo Kim, Hyuk Song, Jeong Woong Lee, Guangming Wu, Hans R Schöler, Jeong Tae Do
Naive and primed pluripotent stem cells (PSCs) and germ cells express the Oct4 gene. The Oct4 gene contains two cis-regulatory elements, the distal enhancer (DE) and proximal enhancer (PE), which differentially control Oct4 expression in a cell-type-specific and stage-specific manner. Here, we generated double transgenic mice carrying both Oct4-ΔPE-GFP and Oct4-ΔDE-tdTomato (RFP), enabling us to simultaneously monitor the activity of DE and PE. Oct4 expression is stage-specifically regulated by DE and PE during embryonic and germ cell development...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/28157205/epex-epcam-and-oct4-or-klf4-alone-are-sufficient-to-generate-induced-pluripotent-stem-cells-through-stat3-and-hif2%C3%AE
#13
I-I Kuan, Kang-Hao Liang, Yi-Ping Wang, Ting-Wen Kuo, Yaa-Jyuhn James Meir, Sareina Chiung-Yuan Wu, Shang-Chih Yang, Jean Lu, Han-Chung Wu
Epithelial cell adhesion molecule (EpCAM) was reported to be cleaved into extracellular domain of EpCAM (EpEX) and intracellular domain of EpCAM (EpICD). We previously reported that EpCAM serves as a potent stem cell marker which is highly and selectively expressed by undifferentiated rather than differentiated hESC. However, the functional role of EpCAM remains elusive. Here, we found that EpEX and EpCAM enhance the efficiency of OSKM reprogramming. Interestingly, Oct4 or Klf4 alone, but not Sox2, can successfully reprogram fibroblasts into iPSCs with EpEX and EpCAM...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28155862/synergetic-effects-of-dna-methylation-and-histone-modification-during-mouse-induced-pluripotent-stem-cell-generation
#14
Guiying Wang, Rong Weng, Yuanyuan Lan, Xudong Guo, Qidong Liu, Xiaoqin Liu, Chenqi Lu, Jiuhong Kang
DNA methylation and histone methylation (H3K27me3) have been reported as major barriers to induced pluripotent stem cell (iPSC) generation using four core transcription factors (Oct4, Sox2, Klf4, and c-Myc, termed OSKM). Here, to illustrate the possibility of deriving iPSCs via demethylation, as well as the exact effects of DNA methylation and histone modification on gene expression regulation, we performed RNA sequencing to characterize the transcriptomes of ES cells and iPSCs derived by demethylation with miR-29b or shDnmt3a, and carried out integrated analyses...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28153093/human-amniocytes-are-receptive-to-chemically-induced-reprogramming-to-pluripotency
#15
Kate E Hawkins, Dafni Moschidou, Danilo Faccenda, Wasco Wruck, Alex Martin-Trujillo, Kwan-Leong Hau, Anna Maria Ranzoni, Veronica Sanchez-Freire, Fabio Tommasini, Simon Eaton, Paolo De Coppi, David Monk, Michelangelo Campanella, Adrian J Thrasher, James Adjaye, Pascale V Guillot
Restoring pluripotency using chemical compounds alone would be a major step forward in developing clinical-grade pluripotent stem cells, but this has not yet been reported in human cells. We previously demonstrated that VPA_AFS cells, human amniocytes cultivated with valproic acid (VPA) acquired functional pluripotency while remaining distinct from human embryonic stem cells (hESCs), questioning the relationship between the modulation of cell fate and molecular regulation of the pluripotency network. Here, we used single-cell analysis and functional assays to reveal that VPA treatment resulted in a homogeneous population of self-renewing non-transformed cells that fulfill the hallmarks of pluripotency, i...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28146140/tumor-and-normal-thyroid-spheroids-from-tissues-to-zebrafish
#16
Valentina Cirello, Germano Gaudenzi, Elisa S Grassi, Carla Colombo, Leonardo Vicentini, Stefano Ferrero, Luca Persani, Giovanni Vitale, Laura Fugazzola
BACKGROUND: Multicellular spheroids represent an interesting experimental model with promising applications in the pre-clinical studies on anticancer drugs. We recently demonstrated that thyroid spheroids recapitulate the features of the original tissues, in either the differentiated and "stem-like" components. Here we were aimed to characterize thyroid spheroids and to investigate in vivo the proangiogenic potential of patient-derived xenografts (PDX) of spheroids obtained from papillary thyroid cancer (PTC) and the matched normal tissues...
January 31, 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/28145881/il-17b-activated-mesenchymal-stem-cells-enhance-proliferation-and-migration-of-gastric-cancer-cells
#17
Qingli Bie, Bin Zhang, Caixia Sun, Xiaoyun Ji, Prince Amoah Barnie, Chen Qi, Jingjing Peng, Danyi Zhang, Dong Zheng, Zhaoliang Su, Shengjun Wang, Huaxi Xu
Mesenchymal stem cells are important cells in tumor microenvironment. We have previously demonstrated that IL-17B/IL-17RB signal promoted progression of gastric cancer. In this study, we further explored the effect of IL-17B on mesenchymal stem cells in tumor microenvironment and its impact on the tumor progression. The results showed that IL-17B induced the expression of stemness-related genes Nanog, Sox2, and Oct4 in mesenchymal stem cells and enhanced its tumor-promoting effect. The supernatant from cultured mesenchymal stem cells after treating with exogenous rIL-17B promoted the proliferation and migration of MGC-803, therefor suggesting that rIL-17B might promote mesenchymal stem cells to produce soluble factors...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28145507/transplanted-mir-219-overexpressing-oligodendrocyte-precursor-cells-promoted-remyelination-and-improved-functional-recovery-in-a-chronic-demyelinated-model
#18
Hong-Bin Fan, Li-Xia Chen, Xue-Bin Qu, Chuan-Lu Ren, Xiu-Xiang Wu, Fu-Xing Dong, Bao-Le Zhang, Dian-Shuai Gao, Rui-Qin Yao
Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28139300/identification-of-a-novel-12-bp-insertion-deletion-indel-of-ips-related-oct4-gene-and-its-association-with-reproductive-traits-in-male-piglets
#19
Fa Ren, Shuai Yu, Rui Chen, Xiaoyan Lv, Chuanying Pan
As a key factor of cellular reprogramming, Oct4 is one of vital transcription factors for induced pluripotent stem cells (iPSCs). Loss of its function or deletion causes apoptosis in primordial germ cells (PGCs), which affect reproductive traits in mammals. In this study, a novel 12-bp insertion/deletion (indel) polymorphism (NC_010449:g.2759-2760insGGTTTTTGTCTA) within the Oct4 gene was identified in 442 pigs of Large White (LW) and Landrace (LD) breeds, showing three genotypes designated as II, ID, and DD...
January 23, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28124980/evolutionary-conservation-of-pou5f3-genomic-organization-and-its-dynamic-distribution-during-embryogenesis-and-in-adult-gonads-in-japanese-flounder-paralichthys-olivaceus
#20
Jinning Gao, Xubo Wang, Quanqi Zhang
Octamer-binding transcription factor 4 (Oct4) is a member of POU (Pit-Oct-Unc) transcription factor family Class V that plays a crucial role in maintaining the pluripotency and self-renewal of stem cells. Though it has been deeply investigated in mammals, its lower vertebrate homologue, especially in the marine fish, is poorly studied. In this study, we isolated the full-length sequence of Paralichthys olivaceus pou5f3 (Popou5f3), and we found that it is homologous to mammalian Oct4. We identified two transcript variants with different lengths of 3'-untranslated regions (UTRs) generated by alternative polyadenylation (APA)...
January 23, 2017: International Journal of Molecular Sciences
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