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https://www.readbyqxmd.com/read/28500655/discovery-and-validation-of-candidate-host-dna-methylation-markers-for-detection-of-cervical-precancer-and-cancer
#1
Megan A Clarke, Patricia Luhn, Julia C Gage, Clara Bodelon, S Terence Dunn, Joan Walker, Rosemary Zuna, Stephen Hewitt, J Keith Killian, Liying Yan, Andrew Miller, Mark Schiffman, Nicolas Wentzensen
Human papillomavirus (HPV) testing has been recently introduced as an alternative to cytology for cervical cancer screening. However, since most HPV infections clear without causing clinically relevant lesions, additional triage tests are required to identify women who are at high risk of developing cancer. We performed DNA methylation profiling on formalin-fixed, paraffin-embedded tissue specimens from women with benign HPV16 infection and histologically confirmed cervical intraepithelial neoplasia grade 3 (CIN3), and cancer using a bead-based microarray covering 1,500 CpG sites in over 800 genes...
May 13, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28432216/embryonic-cholecystitis-and-defective-gallbladder-contraction-in-the-sox17-haploinsufficient-model-of-biliary-atresia
#2
Hiroki Higashiyama, Aisa Ozawa, Hiroyuki Sumitomo, Mami Uemura, Ko Fujino, Hitomi Igarashi, Kenya Imaimatsu, Naoki Tsunekawa, Yoshikazu Hirate, Masamichi Kurohmaru, Yukio Saijoh, Masami Kanai-Azuma, Yoshiakira Kanai
The gallbladder excretes cytotoxic bile acids to the duodenum through the cystic duct and common bile duct system. Sox17 haploinsufficiency causes the biliary atresia-like phenotypes and hepatitis in late organogenesis mouse embryos. However, the molecular and cellular mechanisms in the Sox17-haploinsufficient gallbladder and liver in the etiology of biliary atresia remain unclear. In this study, transcriptomic analyses revealed the early onset of cholecystitis in the Sox17(+/-) embryos, together with the appearance of ectopic cystic duct-like epithelia in their gallbladders...
April 21, 2017: Development
https://www.readbyqxmd.com/read/28412976/hepatic-population-derived-from-human-pluripotent-stem-cells-is-effectively-increased-by-selective-removal-of-undifferentiated-stem-cells-using-ym155
#3
Seok-Jin Kang, Young-Il Park, So-Ryeon Hwang, Hee Yi, Nga Tham, Hyun-Ok Ku, Jae-Young Song, Hwan-Goo Kang
BACKGROUND: Pluripotent stem cells (PSCs) such as embryonic stem cells and induced pluripotent stem cells are promising target cells for cell regenerative medicine together with recently advanced technology of in-vitro differentiation. However, residual undifferentiated stem cells (USCs) during in-vitro differentiation are considered a potential risk for development of cancer cells and nonspecific lineage cell types. In this study we observed that USCs still exist during hepatic differentiation, consequently resulting in poor quality of the hepatic population and forming teratoma in vivo...
April 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28381471/sox17-regulates-conversion-of-human-fibroblasts-into-endothelial-cells-and-erythroblasts-via-de-differentiation-into-cd34-progenitor-cells
#4
Lianghui Zhang, Ankit Jambusaria, Zhigang Hong, Glenn Marsboom, Peter T Toth, Brittney-Shea Herbert, Asrar B Malik, Jalees Rehman
Background -The mechanisms underlying the de-differentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is not known whether fibroblast de-differentiation recapitulates the generation of multipotent progenitors during embryonic development which give rise to endothelial and hematopoietic cell lineages. Here we established the role of the developmental transcription factor SOX17 in regulating the bi-lineage conversion of fibroblasts via the generation of intermediate progenitors...
April 5, 2017: Circulation
https://www.readbyqxmd.com/read/28377629/early-embryonic-development-and-spatiotemporal-localization-of-mammalian-primordial-germ-cell-associated-proteins-in-the-basal-rodent-lagostomus-maximus
#5
Noelia P Leopardo, Alfredo D Vitullo
The gene network controlling primordial germ cell (PGC) specification in eutherian mammals has been exhaustively investigated in mice. The egg-cylinder morphology of the mouse embryo is the key event enabling inductive signals from the extra-embryonic ectoderm (ExE) to specify epiblast cells as PGCs early on. We investigated the embryonic development and the spatiotemporal localization of PGC-associated proteins in the basal Hystricognathi rodent Lagostomus maximus. L. maximus develops through a flat-disc epiblast far apart from the ExE...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28342773/generation-of-enhanced-definitive-endoderm-from-human-embryonic-stem-cells-under-an-albumin-insulin-free-and-chemically-defined-condition
#6
Su Qu, Liang Yan, Bo Fang, Shoudong Ye, Ping Li, Shengyang Ge, Jian Wu, Di Qu, Houyan Song
AIM: To enhance survival and generation of definitive endoderm cells from human embryonic stem cells in a simple and reproducible system. MAIN METHODS: Definitive endoderm (DE) differentiation from human embryonic stem cells (hESCs) was induced under a chemical-defined condition withdrawn insulin supplement and serum albumin. We dissected influence of "alternative growth factors", WNT3A, BMP4 and bFGF in activin A-driven differentiation by detection of DE-associated genes expression and cell viability...
April 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28334711/quantitative-proteomics-analysis-of-ischemia-reperfusion-injury-modulated-proteins-in-cardiac-microvascular-endothelial-cells-and-the-protective-role-of-tongxinluo
#7
Qing Li, He-He Cui, Yue-Jin Yang, Xiang-Dong Li, Gui-Hao Chen, Xia-Qiu Tian, Chen Jin, Qiu-Ting Dong, Pei-Sen Huang, Jun Xu
BACKGROUND: The protection of endothelial cells (ECs) against reperfusion injury has received little attention. In this study, we used Tandem Mass Tag (TMT) labeling proteomics to investigate the modulated proteins in an in vitro model of cardiac microvascular endothelial cells (CMECs) subjected to ischemia/reperfusion (I/R) injury and their alteration by traditional Chinese medicine Tongxinluo (TXL). METHODS: Human CMECs were subjected to 2 h of hypoxia followed by 2 h of reoxygenation with different concentrations of TXL Protein expression profiles of CMECs were determined using tandem mass spectrometry...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28298334/erythropoietin-facilitates-definitive-endodermal-differentiation-of-mouse-embryonic-stem-cells-via-activation-of-erk-signaling
#8
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
#9
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...
June 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28237397/sox17-regulates-cholangiocyte-differentiation-and-acts-as-a-tumor-suppressor-in-cholangiocarcinoma
#10
Maite Merino-Azpitarte, Elisa Lozano, María J Perugorria, Aitor Esparza-Baquer, Oihane Erice, Álvaro Santos-Laso, Colm J O'Rourke, Jesper B Andersen, Raúl Jiménez-Agüero, Adelaida Lacasta, Mauro D'Amato, Óscar Briz, Nidhi Jalan-Sakrikar, Robert C Huebert, Kristen M Thelen, Sergio A Gradilone, Ana M Aransay, José L Lavín, Maite G Fernández-Barrena, Ander Matheu, Marco Marzioni, Gregory J Gores, Luis Bujanda, José J G Marin, Jesús 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
#11
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
#12
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
#13
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
#14
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 and 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
#15
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
#16
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
#17
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
#18
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
#19
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 foster better cell adhesion and improve stem cell differentiation. In the current study, after fabrication using electrospinning technique and surface modifications, the characteristics of polyethersulfone (PES) nanofibers were determined by scanning electron microscopy, attenuated total reflection Fourier transform infrared spectroscopy, and 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide (MTT) assay...
May 2017: 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
#20
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
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