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https://www.readbyqxmd.com/read/29779895/identification-and-single-cell-functional-characterization-of-an-endodermally-biased-pluripotent-substate-in-human-embryonic-stem-cells
#1
Thomas F Allison, Andrew J H Smith, Konstantinos Anastassiadis, Jackie Sloane-Stanley, Veronica Biga, Dylan Stavish, James Hackland, Shan Sabri, Justin Langerman, Mark Jones, Kathrin Plath, Daniel Coca, Ivana Barbaric, Paul Gokhale, Peter W Andrews
Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal...
May 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29763649/differentiation-of-umbilical-cord-derived-mesenchymal-stem-cells-to-hepatocyte-cells-by-transfection-of-mir-106a-mir-574-3p-and-mir-451
#2
Maryam Khosravi, Negar Azarpira, Sara Shamdani, Suzzan Hojjat-Assari, Sina Naserian, Mohammad Hossein Karimi
Studying the profile of micro RNAs (miRs) elucidated the highest expressed miRs in hepatic differentiation. In this study, we investigated to clarify the role of three embryonic overexpressed miRs (miR-106a, miR-574-3p and miR-451) during hepatic differentiation of human umbilical cord derived mesenchymal stem cells (UC-MSCs). We furthermore, aimed to explore whether overexpression of any of these miRs alone is sufficient to induce the differentiation of the UC-MSCs into hepatocyte-like cells. UC-MSCs were transfected either alone or together with miR-106a, miR-574-3p and miR-451 and their potential hepatic differentiation and alteration in gene expression profile, morphological changes and albumin secretion ability were investigated...
May 12, 2018: Gene
https://www.readbyqxmd.com/read/29703082/fabrication-of-a-co-culture-micro-bioreactor-device-for-efficient-hepatic-differentiation-of-human-induced-pluripotent-stem-cells-hipscs
#3
Mousa Kehtari, Bahman Zeynali, Masoud Soleimani, Mahboubeh Kabiri, Ehsan Seyedjafari
Primary hepatocytes, as the gold standard cell type for in vitro models, lose their characteristic morphology and functions after few days. There is an urgent need to develop physiologically relevant models that recapitulate liver microenvironment to obtain mature hepatocyte from stem cells. We designed and fabricated a micro-bioreactor device mimicking the physiological shear stress and cell-cell interaction in liver sinusoid microenvironment. Induced pluripotent stem cells (iPSCs) were co-cultured with human umbilical vein endothelial cells (HUVECs) in the micro-bioreactor device with continuous perfusion of hepatic differentiation medium (100 μL/h)...
April 27, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29684040/differentiation-capacities-of-ps-clusters-adult-pituitary-stem-progenitor-cell-clusters-located-in-the-parenchymal-niche-of-the-rat-anterior-lobe
#4
Saishu Yoshida, Naoto Nishimura, Hideaki Yurino, Masaaki Kobayashi, Kotaro Horiguchi, Kentaro Yano, Shin-Ichi Hashimoto, Takako Kato, Yukio Kato
Pituitary endocrine cells are supplied by Sox2-expressing stem/progenitor cells in the anterior lobe of the adult pituitary. In relation to their microenvironment ("niche"), SOX2-positive cells exist in two types of niches; the marginal cell layer-niche and the parenchymal-niche. Recently, we isolated dense stem/progenitor cell clusters from the parenchymal-niche as parenchymal stem/progenitor cell (PS)-clusters. We classified these PS-clusters into three subtypes based on differences in S100β-expression (S100β-positive, -negative, and -mixed type), and reported that S100β-positive PS-clusters exhibited the capacity for differentiation into endocrine cells under 3-dimensional cultivation system...
2018: PloS One
https://www.readbyqxmd.com/read/29666335/identification-molecular-characterization-and-analysis-of-the-expression-pattern-of-soxf-subgroup-genes-the-yellow-river-carp-cyprinus-carpio
#5
Tingting Liang, Yongfang Jia, Ruihua Zhang, Qiyan Du, Zhongjie Chang
Sox7, Sox17 and Sox18 are the members of the Sry-related high-mobility group box family (SoxF) of transcription factors. SoxF factors regulate endothelial cell fate as well as development and differentiation of blood cells and lymphatic vessels. There is very less information about the functions of these genes in fish. We obtained the full-length cDNA sequence of SoxF genes including Sox7, Sox17 and Sox18 in Cyprinus carpio, where Sox7 and Sox18 had two copies. The construction of a phylogenetic tree showed that these genes were homologous to the genes in other species...
March 2018: Journal of Genetics
https://www.readbyqxmd.com/read/29650961/identification-of-rare-sequence-variation-underlying-heritable-pulmonary-arterial-hypertension
#6
Stefan Gräf, Matthias Haimel, Marta Bleda, Charaka Hadinnapola, Laura Southgate, Wei Li, Joshua Hodgson, Bin Liu, Richard M Salmon, Mark Southwood, Rajiv D Machado, Jennifer M Martin, Carmen M Treacy, Katherine Yates, Louise C Daugherty, Olga Shamardina, Deborah Whitehorn, Simon Holden, Micheala Aldred, Harm J Bogaard, Colin Church, Gerry Coghlan, Robin Condliffe, Paul A Corris, Cesare Danesino, Mélanie Eyries, Henning Gall, Stefano Ghio, Hossein-Ardeschir Ghofrani, J Simon R Gibbs, Barbara Girerd, Arjan C Houweling, Luke Howard, Marc Humbert, David G Kiely, Gabor Kovacs, Robert V MacKenzie Ross, Shahin Moledina, David Montani, Michael Newnham, Andrea Olschewski, Horst Olschewski, Andrew J Peacock, Joanna Pepke-Zaba, Inga Prokopenko, Christopher J Rhodes, Laura Scelsi, Werner Seeger, Florent Soubrier, Dan F Stein, Jay Suntharalingam, Emilia M Swietlik, Mark R Toshner, David A van Heel, Anton Vonk Noordegraaf, Quinten Waisfisz, John Wharton, Stephen J Wort, Willem H Ouwehand, Nicole Soranzo, Allan Lawrie, Paul D Upton, Martin R Wilkins, Richard C Trembath, Nicholas W Morrell
Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-β pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29626713/differentiation-of-hepatocyte-like-cells-from-human-pluripotent-stem-cells-using-small-molecules
#7
Faizal Z Asumda, Konstantinos E Hatzistergos, Derek M Dykxhoorn, Silvia Jakubski, Jasmine Edwards, Emmanuel Thomas, Eugene R Schiff
A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific differentiation into definitive endoderm, hepatoblast and hepatocyte-like derivatives...
March 27, 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29549430/cells-with-hematopoietic-potential-reside-within-mouse-proepicardium
#8
Ewa Jankowska-Steifer, Justyna Niderla-Bielińska, Bogdan Ciszek, Marek Kujawa, Mateusz Bartkowiak, Aleksandra Flaht-Zabost, Daria Klosinska, Anna Ratajska
During embryonic development, hematopoietic cells are present in areas of blood-vessel differentiation. These hematopoietic cells emerge from a specific subpopulation of endothelial cells called the hemogenic endothelium. We have previously found that mouse proepicardium contained its own population of endothelial cells forming a network of vascular tubules. We hypothesize that this EC population contains cells of hematopoietic potential. Therefore, we investigated an in vitro hematopoietic potential of proepicardial cell populations...
March 16, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29541226/sox2-and-sox12-are-predictive-of-prognosis-in-patients-with-clear-cell-renal-cell-carcinoma
#9
Weijie Gu, Beihe Wang, Fangning Wan, Junlong Wu, Xiaolin Lu, Hongkai Wang, Yao Zhu, Hailiang Zhang, Guohai Shi, Bo Dai, Dingwei Ye
Sex-determining region Y-box protein (SOX) genes serve an important role in cancer growth and metastasis. The present study aimed to determine the predictive ability of SOX and associated genes identified through molecular network in clear cell renal cell carcinoma (RCC). A total of 505 patients with clear cell RCC from The Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression profile of SOX and associated genes were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, gender, tumor grade, stage, laterality disease-free-survival and overall survival (OS) were collected...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29533390/human-pluripotent-stem-cell-derived-hlc-transcriptome-data-enables-molecular-dissection-of-hepatogenesis
#10
Wasco Wruck, James Adjaye
Induced pluripotent stem cells (iPSCs) and human embryonic stem cells (hESCs) differentiated into hepatocyte-like cells (HLCs) provide a defined and renewable source of cells for drug screening, toxicology and regenerative medicine. We previously reprogrammed human fetal foreskin fibroblast cells (HFF1) into iPSCs employing an episomal plasmid-based integration-free approach, this iPSC-line and the hESC lines H1 and H9 were used to model hepatogenesis in vitro. Biochemical characterisation confirmed glycogen storage, ICG uptake and release, urea and bile acid production, as well as CYP3A4 activity...
March 13, 2018: Scientific Data
https://www.readbyqxmd.com/read/29528446/characterization-of-migratory-primordial-germ-cells-in-the-aorta-gonad-mesonephros-of-a-4-5-week-old-human-embryo-a-toolbox-to-evaluate-in-vitro-early-gametogenesis
#11
Maria Gomes Fernandes, Monika Bialecka, Daniela C F Salvatori, Susana M Chuva de Sousa Lopes
STUDY QUESTION: Which set of antibodies can be used to identify migratory and early post-migratory human primordial germ cells (hPGCs)? STUDY FINDING: We validated the specificity of 33 antibodies for 31 markers, including POU5F1, NANOG, PRDM1 and TFAP2C as specific markers of hPGCs at 4.5 weeks of development of Carnegie stage (CS12-13), whereas KIT and SOX17 also marked the intra-aortic hematopoietic stem cell cluster in the aorta-gonad-mesonephros (AGM). WHAT IS KNOWN ALREADY: The dynamics of gene expression during germ cell development in mice is well characterized and this knowledge has proved crucial to allow the development of protocols for the in-vitro derivation of functional gametes...
March 8, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29458175/maintenance-of-hematopoietic-stem-and-progenitor-cells-in-fetal-intra-aortic-hematopoietic-clusters-by-the-sox17-notch1-hes1-axis
#12
Kiyoka Saito, Ikuo Nobuhisa, Kaho Harada, Satomi Takahashi, Maha Anani, Heiko Lickert, Masami Kanai-Azuma, Yoshiakira Kanai, Tetsuya Taga
The aorta-gonad-mesonephros region, from which definitive hematopoiesis first arises in midgestation mouse embryos, has intra-aortic hematopoietic clusters (IAHCs) containing hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). We previously reported expression of the transcription factor Sox17 in IAHCs, and overexpression of Sox17 in CD45low c-KIThigh cells comprising IAHCs maintains the formation of cell clusters and their multipotency in vitro over multiple passages. Here, we demonstrate the importance of NOTCH1 in IAHC formation and maintenance of the HSC/HPC phenotype...
April 1, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29444818/sox7-promotes-high-grade-glioma-by-increasing-vegfr2-mediated-vascular-abnormality
#13
Il-Kug Kim, Kangsan Kim, Eunhyeong Lee, Dong Sun Oh, Chan Soon Park, Seongyeol Park, Jee Myung Yang, Ju-Hee Kim, Hyung-Seok Kim, David T Shima, Jeong Hoon Kim, Seok Ho Hong, Young Hyun Cho, Young Hoon Kim, Jong Bae Park, Gou Young Koh, Young Seok Ju, Heung Kyu Lee, Seungjoo Lee, Injune Kim
High-grade glioma (HGG) is highly angiogenic, but antiangiogenic therapy has transient clinical benefit in only a fraction of patients. Vascular regulators of these heterogeneous responses remain undetermined. We found up-regulation of Sox7 and down-regulation of Sox17 in tumor endothelial cells (tECs) in mouse HGG. Sox7 deletion suppressed VEGFR2 expression, vascular abnormality, hypoxia-driven invasion, regulatory T cell infiltration, and tumor growth. Conversely, Sox17 deletion exacerbated these phenotypes by up-regulating Sox7 in tECs...
March 5, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29435983/epigenetic-dysregulation-of-key-developmental-genes-in-radiation-induced-rat-mammary-carcinomas
#14
Kazuhiro Daino, Mayumi Nishimura, Tatsuhiko Imaoka, Masaru Takabatake, Takamitsu Morioka, Yukiko Nishimura, Yoshiya Shimada, Shizuko Kakinuma
With the increase in the number of long-term cancer survivors worldwide, there is a growing concern about the risk of secondary cancers induced by radiotherapy. Epigenetic modifications of genes associated with carcinogenesis are attractive targets for the prevention of cancer owing to their reversible nature. To identify genes with possible changes in functionally relevant DNA methylation patterns in mammary carcinomas induced by radiation exposure, we performed microarray-based global DNA methylation and expression profiling in γ-ray-induced rat mammary carcinomas and normal mammary glands...
February 13, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29320761/expandable-arterial-endothelial-precursors-from-human-cd34-cells-differ-in-their-proclivity-to-undergo-an-endothelial-to-mesenchymal-transition
#15
Auston Z Miller, Alexander Satchie, Alex P Tannenbaum, Aman Nihal, James A Thomson, David T Vereide
Arterial diseases continue to pose a major health concern but in vitro studies are limited because explanted cells can exhibit poor proliferative capacity and a loss of specificity. Here, we find that two transcription factors, MYCN and SOX17, induce and indefinitely expand in culture precursors of human arterial endothelial cells (expandable arterial endothelial precursors [eAEPs]). The eAEPs are derived from CD34+ cells found in umbilical cord blood or adult bone marrow. Independent eAEP lines differ in their proclivity to undergo an endothelial-to-mesenchymal transition (EndoMT), a hallmark event in a broad array of vascular diseases and disorders...
January 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29298619/developing-a-cost-effective-and-scalable-production-of-human-hepatic-competent-endoderm-from-size-controlled-pluripotent-stem-cell-aggregates
#16
Zahra Farzaneh, Mostafa Najarasl, Saeed Abbasalizadeh, Massoud Vosough, Hossein Baharvand
Dynamic suspension culture of human pluripotent stem cells (hPSCs) in stirred bioreactors provides a valuable scalable culture platform for integrated differentiation toward different lineages for potential research and therapeutic applications. However, current protocols for scalable and integrated differentiation of hPSCs limited due to high cost of growth factors and technical challenges. Here, hPSCs aggregates primed with 6 and 12 μM of CHIR99021 (CHIR), a Wnt agonist, in combination with different concentrations of high cost Activin A (10, 25, 50, 100 ng/mL)...
February 15, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29191544/association-of-sox17-gene-polymorphisms-and-intracranial-aneurysm-a-case-control-study-and-meta-analysis
#17
Eun Pyo Hong, Bong Jun Kim, Chulho Kim, Hyuk Jai Choi, Jin Pyeong Jeon
BACKGROUND: Genome-wide association studies have revealed an association between SRY-box 17 (SOX17) gene and intracranial aneurysm (IA) formation. However, results were mainly derived from European and Japanese populations. We investigated the association between SOX17 gene polymorphisms and IA in a homogeneous Korean population. We performed a meta-analysis to assess these results in East-Asian populations. METHODS: This cross-sectional study included 187 age- and sex-matched patients with IA and 372 control subjects...
February 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29190932/multigene-methylation-analysis-of-enriched-circulating-tumor-cells-associates-with-poor-progression-free-survival-in-metastatic-breast-cancer-patients
#18
Theresa Benezeder, Verena Tiran, Alexandra A N Treitler, Christoph Suppan, Christopher Rossmann, Herbert Stoeger, Richard J Cote, Ram H Datar, Marija Balic, Nadia Dandachi
Blood-based biomarkers such as circulating tumor cells (CTCs) provide dynamic real-time assessment of molecular tumor characteristics beyond the primary tumor. The aim of this study was to evaluate the feasibility of a size-based microfilter to assess multigene methylation analysis of enriched CTCs in a prospective proof-of principle study. We examined the quantitative methylation status of nine genes ( AKR1B1, BMP6, CST6, HOXB4, HIST1H3C, ITIH5, NEUROD1, RASSF1, SOX17 ) in enriched CTCs from metastatic breast cancer patients...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29166607/kdm2b-regulates-somatic-reprogramming-through-variant-prc1-complex-dependent-function
#19
Zhiwei Zhou, Xuejie Yang, Jiangping He, Jing Liu, Fang Wu, Shengyong Yu, Yuting Liu, Runxia Lin, He Liu, Yuanbin Cui, Chunhua Zhou, Xiaoshan Wang, Jian Wu, Shangtao Cao, Lin Guo, Lihui Lin, Tao Wang, Xiaozhong Peng, Boqing Qiang, Andrew P Hutchins, Duanqing Pei, Jiekai Chen
Polycomb repressive complex 1 (PRC1) plays essential roles in cell-fate determination. Recent studies have found that the composition of mammalian PRC1 is particularly varied and complex; however, little is known about the functional consequences of these variant PRC1 complexes on cell-fate determination. Here, we show that Kdm2b promotes Oct4-induced somatic reprogramming through recruitment of a variant PRC1 complex (PRC1.1) to CpG islands (CGIs). Furthermore, we find that bone morphogenetic protein (BMP) represses Oct4/Kdm2b-induced somatic reprogramming selectively...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29090037/performance-of-a-methylation-specific-real-time-pcr-assay-as-a-triage-test-for-hpv-positive-women
#20
Martina Schmitz, Kristina Wunsch, Heike Hoyer, Cornelia Scheungraber, Ingo B Runnebaum, Alfred Hansel, Matthias Dürst
BACKGROUND: HPV DNA testing as a primary screening marker is being implemented in several countries. Due to the high HPV prevalence in the screening population, effective triage strategies for HPV-positive cases are required. The aim of this study was to evaluate the performance of a methylation-specific real-time PCR  assay (GynTect®) comprising six marker regions as a triage test. RESULTS: An analytical sensitivity of 0.1 ng genomic DNA corresponding to 15 SiHa cells was achieved...
2017: Clinical Epigenetics
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