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https://www.readbyqxmd.com/read/28298334/erythropoietin-facilitates-definitive-endodermal-differentiation-of-mouse-embryonic-stem-cells-via-activation-of-erk-signaling
#1
Taku Kaitsuka, Kohei Kobayashi, Wakako Otsuka, Takuya Kubo, Farzana Hakim, Fan-Yan Wei, Nobuaki Shiraki, Shoen Kume, Kazuhito Tomizawa
Artificially generated pancreatic β-cells from pluripotent stem cells are expected for cell replacement therapy for type 1 diabetes. Several strategies are adopted to direct pluripotent stem cells toward pancreatic differentiation. However, a standard differentiation method for clinical application has not been established. It is important to develop more effective and safer methods for generating pancreatic β-cells without toxic or mutagenic chemicals. In the present study, we screened several endogenous factors involved in organ development to identify the factor, which induced the efficiency of pancreatic differentiation and found that treatment with erythropoietin (EPO) facilitated the differentiation of mouse embryonic stem cells (ESCs) into definitive endoderm...
March 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28283910/hyperglycemia-impedes-definitive-endoderm-differentiation-of-human-embryonic-stem-cells-by-modulating-histone-methylation-patterns
#2
A C H Chen, Y L Lee, S W Fong, C C Y Wong, E H Y Ng, W S B Yeung
Exposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency...
March 10, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28237397/sox17-regulates-cholangiocyte-differentiation-and-acts-as-a-tumor-suppressor-in-cholangiocarcinoma
#3
M Merino-Azpitarte, E Lozano, M J Perugorria, A Esparza-Baquer, O Erice, A Santos-Laso, C J O'Rourke, J B Andersen, R Jiménez-Agüero, A Lacasta, M D'Amato, O Briz, N Jalan-Sakrikar, R C Huebert, K M Thelen, S A Gradilone, A M Aransay, J L Lavín, M G Fernández-Barrena, A Matheu, M Marzioni, G J Gores, L Bujanda, J J G Marin, J M Banales
BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a biliary malignancy linked to genetic and epigenetic abnormalities, such as hypermethylation of SOX17 promoter. Here, the role of SOX17 in cholangiocyte differentiation and cholangiocarcinogenesis was studied. METHODS: SOX17 expression/function was evaluated along the differentiation of human induced pluripotent stem cells (iPSC) into cholangiocytes, in the dedifferentiation process of normal human cholangiocytes (NHC) in culture and in cholangiocarcinogenesis...
February 22, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28235674/thrombopoietin-contributes-to-the-formation-and-the-maintenance-of-hematopoietic-progenitor-containing-cell-clusters-in-the-aorta-gonad-mesonephros-region
#4
Kaho Harada, Ikuo Nobuhisa, Maha Anani, Kiyoka Saito, Tetsuya Taga
In the midgestation mouse embryo, hematopoietic cell clusters containing hematopoietic stem/progenitor cells arise in the aorta-gonad-mesonephros (AGM) region. We have previously reported that forced expression of the Sox17 transcription factor in CD45(low)c-Kit(high) AGM cells, which are the hematopoietic cellular component of the cell clusters, and subsequent coculture with OP9 stromal cells in the presence of three cytokines, stem cell factor (SCF), interleukin-3 (IL-3), and thrombopoietin (TPO), led to the formation and the maintenance of cell clusters with cells at an undifferentiated state in vitro...
February 21, 2017: Cytokine
https://www.readbyqxmd.com/read/28185954/wip1-directly-dephosphorylates-nlk-and-increases-wnt-activity-during-germ-cell-development
#5
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), enhancing its interaction with β-catenin...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28152181/purification-of-definitive-endoderm-generated-from-pluripotent-stem-cells-by-magnetic-cell-sorting
#6
Ulf Diekmann, Claudia Davenport, Jasmin Kresse, Ortwin Naujok
Pluripotent stem cells have the capability to differentiate into any somatic cell type of the human body. The generation of surrogate cells for the treatment of liver, lung, and pancreatic diseases is of great medical interest. First, the in vitro formation into cells of the definitive endoderm is required. Upon commitment into this lineage, the cells express transcription factors such as FOXA2, SOX17, HNF1B; GATA family members; and the surface protein CXCR4. Unfortunately, some pluripotent stem cells resist the differentiation and contaminate the culture...
February 2, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28148542/predicting-the-grade-of-dysplasia-of-pancreatic-cystic-neoplasms-using-cyst-fluid-dna-methylation-markers
#7
Tatsuo Hata, Marco Dal Molin, Seung-Mo Hong, Koji Tamura, Masaya Suenaga, Jun Yu, Hiraku Sedogawa, Matthew J Weiss, Christopher L Wolfgang, Anne Marie Lennon, Ralph H Hruban, Michael G Goggins
PURPOSE: Pancreatic cysts are common and pose diagnostic and management challenges. Pancreatic cyst fluid markers have the potential to aid in the management of cysts with concerning imaging findings. Our aim was to evaluate cyst fluid methylated DNA markers for their accuracy for predicting the histologic grade of neoplastic pancreatic cysts. EXPERIMENTAL DESIGN: Pancreatic cyst fluid samples from 183 patients (29 discovery, 154 validation) aspirated after surgical resection were analyzed for methylated DNA at selected genes (SOX17, BNIP3, FOXE1, PTCHD2, SLIT2, EYA4 and SFRP1) using methylation-specific droplet-digital PCR (dd-QMSP)...
February 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28132771/structural-insight-mutation-and-interactions-in-human-beta-catenin-and-sox17-protein-a-molecular-level-outlook-for-organogenesis
#8
Arundhati Banerjee, Sujay Ray
Essential human proteins; SOX17-HMG domain and beta-catenin uphold a major responsibility for vertebrate gastrulation and embryonic development. Earlier experimental assays document their interaction and states that upon M76A and G103R mutation, their interaction varied. Till date, there was no computational analysis for either of proteins as well as their respective residues for the interaction. The present study extracted and analyzed the experimentally validated 3D models of SOX17-HMG domain and beta-catenin...
April 30, 2017: Gene
https://www.readbyqxmd.com/read/28094799/activation-of-wnt-%C3%AE-catenin-signalling-via-gsk3-inhibitors-direct-differentiation-of-human-adipose-stem-cells-into-functional-hepatocytes
#9
Jieqiong Huang, Xinyue Guo, Weihong Li, Haiyan Zhang
The generation of hepatocytes that are derived from human adipose stem cells (hASCs) represents an alternative to human hepatocytes for individualized therapeutic and pharmaceutical applications. However, the mechanisms facilitating hepatocyte differentiation from hASCs are not well understood. Here, we show that upon exposure to glycogen synthase kinase 3 (GSK3) inhibitors alone, the expression of definitive endoderm specific genes GATA4, FOXA2, and SOX17 in hASCs significantly increased in a manner with activation of Wnt/β-catenin signalling...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28091527/sox17-drives-functional-engraftment-of-endothelium-converted-from-non-vascular-cells
#10
William Schachterle, Chaitanya R Badwe, Brisa Palikuqi, Balvir Kunar, Michael Ginsberg, Raphael Lis, Masataka Yokoyama, Olivier Elemento, Joseph M Scandura, Shahin Rafii
Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies...
January 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/27937745/ionizing-radiation-alters-human-embryonic-stem-cell-properties-and-differentiation-capacity-by-diminishing-the-expression-of-activin-receptors
#11
Sabine Luft, Onetsine Arrizabalaga, Ireen Kulish, Elena Nasonova, Marco Durante, Sylvia Ritter, Insa S Schroeder
Exposure of the embryo to ionizing radiation (IR) is detrimental as it can cause genotoxic stress leading to immediate and latent consequences such as functional defects, malformations, or cancer. Human embryonic stem (hES) cells can mimic the preimplantation embryo and help to assess the biological effects of IR during early development. In this study, we describe the alterations H9 hES cells exhibit after X-ray irradiation in respect to cell cycle progression, apoptosis, genomic stability, stem cell signaling, and their capacity to differentiate into definitive endoderm...
December 22, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27861428/hepatogenic-differentiation-of-human-induced-pluripotent-stem-cells-on-collagen-coated-polyethersulfone-nanofibers
#12
Maryam Mahmoodinia Maymand, Hamid Reza Soleimanpour-Lichaei, Abdolreza Ardeshirylajimi, Masoud Soleimani, Samaneh Mirzaei, Athena Hajarizadeh, Maryam Kabir Salmani
Many scientists have been fascinated with Induced pluripotent stem cells (iPSCs) for cell replacement therapies. Nanofibrous biocompatible scaffolds have been shown to promote better cell adhesion and improve stem cell differentiation. In the present study, after fabrication using electrospinning technique and surface modifications, the characteristics of Polyethersulfone (PES) nanofibers were determined by scanning electron microscopy (SEM), ATR-FTIR and MTT assay. Then, the hepatogenic potential of iPSCs was evaluated using Real-Time RT-PCR and immunocytochemistry (ICC) after culture on collagen coated polyethersulfone (PES/COL) scaffolds...
November 15, 2016: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/27852316/defined-three-dimensional-culture-conditions-mediate-efficient-induction-of-definitive-endoderm-lineage-from-human-umbilical-cord-wharton-s-jelly-mesenchymal-stem-cells
#13
Ashraf Al Madhoun, Hamad Ali, Sarah AlKandari, Valerie Lopez Atizado, Nadeem Akhter, Fahd Al-Mulla, Maher Atari
BACKGROUND: Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are gaining increasing interest as an alternative source of stem cells for regenerative medicine applications. Definitive endoderm (DE) specification is a prerequisite for the development of vital organs such as liver and pancreas. Hence, efficient induction of the DE lineage from stem cells is crucial for subsequent generation of clinically relevant cell types. Here we present a defined 3D differentiation protocol of WJ-MSCs into DE cells...
November 16, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27824029/dna-methylation-and-chromatin-accessibility-profiling-of-mouse-and-human-fetal-germ-cells
#14
Hongshan Guo, Boqiang Hu, Liying Yan, Jun Yong, Yan Wu, Yun Gao, Fan Guo, Yu Hou, Xiaoying Fan, Ji Dong, Xiaoye Wang, Xiaohui Zhu, Jie Yan, Yuan Wei, Hongyan Jin, Wenxin Zhang, Lu Wen, Fuchou Tang, Jie Qiao
Chromatin remodeling is important for the epigenetic reprogramming of human primordial germ cells. However, the comprehensive chromatin state has not yet been analyzed for human fetal germ cells (FGCs). Here we use nucleosome occupancy and methylation sequencing method to analyze both the genome-wide chromatin accessibility and DNA methylome at a series of crucial time points during fetal germ cell development in both human and mouse. We find 116 887 and 137 557 nucleosome-depleted regions (NDRs) in human and mouse FGCs, covering a large set of germline-specific and highly dynamic regulatory genomic elements, such as enhancers...
February 2017: Cell Research
https://www.readbyqxmd.com/read/27814480/inhibition-of-apoptosis-overcomes-stage-related-compatibility-barriers-to-chimera-formation-in-mouse-embryos
#15
Hideki Masaki, Megumi Kato-Itoh, Yusuke Takahashi, Ayumi Umino, Hideyuki Sato, Keiichi Ito, Ayaka Yanagida, Toshinobu Nishimura, Tomoyuki Yamaguchi, Masumi Hirabayashi, Takumi Era, Kyle M Loh, Sean M Wu, Irving L Weissman, Hiromitsu Nakauchi
Cell types more advanced in development than embryonic stem cells, such as EpiSCs, fail to contribute to chimeras when injected into pre-implantation-stage blastocysts, apparently because the injected cells undergo apoptosis. Here we show that transient promotion of cell survival through expression of the anti-apoptotic gene BCL2 enables EpiSCs and Sox17(+) endoderm progenitors to integrate into blastocysts and contribute to chimeric embryos. Upon injection into blastocyst, BCL2-expressing EpiSCs contributed to all bodily tissues in chimeric animals while Sox17(+) endoderm progenitors specifically contributed in a region-specific fashion to endodermal tissues...
November 3, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27802172/interplay-between-sox7-and-runx1-regulates-hemogenic-endothelial-fate-in-the-yolk-sac
#16
Andrew J Lilly, Guilherme Costa, Anne Largeot, Muhammad Z H Fadlullah, Michael Lie-A-Ling, Georges Lacaud, Valerie Kouskoff
Endothelial to hematopoietic transition (EHT) is a dynamic process involving the shutting down of endothelial gene expression and switching on of hematopoietic gene transcription. Although the factors regulating EHT in hemogenic endothelium (HE) of the dorsal aorta have been relatively well studied, the molecular regulation of yolk sac HE remains poorly understood. Here, we show that SOX7 inhibits the expression of RUNX1 target genes in HE, while having no effect on RUNX1 expression itself. We establish that SOX7 directly interacts with RUNX1 and inhibits its transcriptional activity...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27748754/differentiation-of-human-embryonic-stem-cells-to-hoxa-hemogenic-vasculature-that-resembles-the-aorta-gonad-mesonephros
#17
Elizabeth S Ng, Lisa Azzola, Freya F Bruveris, Vincenzo Calvanese, Belinda Phipson, Katerina Vlahos, Claire Hirst, Vanta J Jokubaitis, Qing C Yu, Jovana Maksimovic, Simone Liebscher, Vania Januar, Zhen Zhang, Brenda Williams, Aude Conscience, Jennifer Durnall, Steven Jackson, Magdaline Costa, David Elliott, David N Haylock, Susan K Nilsson, Richard Saffery, Katja Schenke-Layland, Alicia Oshlack, Hanna K A Mikkola, Edouard G Stanley, Andrew G Elefanty
The ability to generate hematopoietic stem cells from human pluripotent cells would enable many biomedical applications. We find that hematopoietic CD34(+) cells in spin embryoid bodies derived from human embryonic stem cells (hESCs) lack HOXA expression compared with repopulation-competent human cord blood CD34(+) cells, indicating incorrect mesoderm patterning. Using reporter hESC lines to track the endothelial (SOX17) to hematopoietic (RUNX1C) transition that occurs in development, we show that simultaneous modulation of WNT and ACTIVIN signaling yields CD34(+) hematopoietic cells with HOXA expression that more closely resembles that of cord blood...
October 17, 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/27738313/sox17-is-a-tumor-suppressor-in-endometrial-cancer
#18
Yongli Zhang, Wei Bao, Kai Wang, Wen Lu, Huihui Wang, Huan Tong, Xiaoping Wan
β-catenin is a key regulatory factor for the Wnt signaling pathway. SOX17 is an important β-catenin inhibitor, while MAML3 is a co-activator of β-catenin-mediated transcription. Out of 120 endometrial cancer (EC) patients, we found that those with tumors expressing higher SOX17 (n=68) had longer recurrence-free survival (P=0.024), while higher MAML3 expression (n=76) was associated with shorter recurrence-free survival (P=0.022). Immunohistochemical and immunoprecipitation analyses revealed that SOX17 and MAML3 co-localized in EC cell nuclei, and the MAML3 C-terminal region was necessary for SOX17 binding...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27734359/efficient-induction-and-isolation-of-human-primordial-germ-cell-like-cells-from-competent-human-pluripotent-stem-cells
#19
Naoko Irie, M Azim Surani
We recently reported a robust and defined culture system for the specification of human primordial germ cell-like cells (hPGCLCs) from human pluripotent stem cells (hPSCs), both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro (Irie et al. Cell 160: 253-268, 2015). Similar attempts previously produced hPGCLCs from hPSCs at a very low efficiency, and the resulting cells were not fully characterized. A key step, which facilitated efficient hPGCLC specification from hPSCs, was the induction of a "competent" state for PGC fate via the medium containing a cocktail of four inhibitors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27729459/early-detection-of-lung-cancer-using-dna-promoter-hypermethylation-in-plasma-and-sputum
#20
Alicia Hulbert, Ignacio Jusue-Torres, Alejandro Stark, Chen Chen, Kristen Rodgers, Beverly Lee, Candace Griffin, Andrew Yang, Peng Huang, John Wrangle, Steven A Belinsky, Tza-Huei Wang, Stephen C Yang, Stephen B Baylin, Malcolm V Brock, James G Herman
PURPOSE: CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of lung cancer screening using ultrasensitive methods and a lung cancer-specific gene panel to detect DNA methylation in sputum and plasma. EXPERIMENTAL DESIGN: This is a case-control study of subjects with suspicious nodules on CT imaging. Plasma and sputum were obtained preoperatively. Cases (n = 150) had pathologic confirmation of node-negative (stages I and IIA) non-small cell lung cancer...
October 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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