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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
November 8, 2016: Cell Research
https://www.readbyqxmd.com/read/27814480/inhibition-of-apoptosis-overcomes-stage-related-compatibility-barriers-to-chimera-formation-in-mouse-embryos
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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 pre-operatively. Cases (n=150) had pathological confirmation of node negative (stage I and IIA) non-small cell lung cancer...
October 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27722841/integrated-analysis-of-gene-expression-and-methylation-profiles-of-48-candidate-genes-in-breast-cancer-patients
#13
Zibo Li, Jianfu Heng, Jinhua Yan, Xinwu Guo, Lili Tang, Ming Chen, Limin Peng, Yepeng Wu, Shouman Wang, Zhi Xiao, Zhongping Deng, Lizhong Dai, Jun Wang
PURPOSE: Gene-specific methylation and expression have shown biological and clinical importance for breast cancer diagnosis and prognosis. Integrated analysis of gene methylation and gene expression may identify genes associated with biology mechanism and clinical outcome of breast cancer and aid in clinical management. METHODS: Using high-throughput microfluidic quantitative PCR, we analyzed the expression profiles of 48 candidate genes in 96 Chinese breast cancer patients and investigated their correlation with gene methylation and associations with breast cancer clinical parameters...
November 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27720607/the-germ-cell-fate-of-cynomolgus-monkeys-is-specified-in-the-nascent-amnion
#14
Kotaro Sasaki, Tomonori Nakamura, Ikuhiro Okamoto, Yukihiro Yabuta, Chizuru Iwatani, Hideaki Tsuchiya, Yasunari Seita, Shinichiro Nakamura, Naoto Shiraki, Tetsuya Takakuwa, Takuya Yamamoto, Mitinori Saitou
The germ cell lineage ensures reproduction and heredity. The mechanism for germ cell specification in primates, including humans, has remained unknown. In primates, upon implantation the pluripotent epiblast segregates the amnion, an extra-embryonic membrane eventually ensheathing an embryo, and thereafter initiates gastrulation to generate three germ layers. Here, we show that in cynomolgus monkeys, the SOX17/TFAP2C/BLIMP1-positive primordial germ cells (cyPGCs) originate from the dorsal amnion at embryonic day 11 (E11) prior to gastrulation...
October 24, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27671002/a-six-cpg-panel-with-dna-methylation-biomarkers-predicting-treatment-response-of-chemoradiation-in-esophageal-squamous-cell-carcinoma
#15
Wei-Lun Chang, Wu-Wei Lai, I-Ying Kuo, Chien-Yu Lin, Pei-Jung Lu, Bor-Shyang Sheu, Yi-Ching Wang
BACKGROUND: Prognosis of esophageal squamous cell carcinoma (ESCC) patients remains poor, and the chemoradiotherapy (CRT) applied to ESCC patients often failed. Therefore, development of biomarkers to predict CRT response is immensely important for choosing the best treatment strategy of an individual patient. METHODS: The methylation array and pyrosequencing methylation assay were performed in pre-treatment endoscopic biopsies to identify probes with differential CpG methylation levels between good and poor CRT responders in a cohort of 12 ESCC patients...
September 26, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27651798/ftir-spectroscopic-and-molecular-analysis-during-differentiation-of-pluripotent-stem-cells-to-pancreatic-cells
#16
Gustavo Jesus Vazquez-Zapien, Monica Maribel Mata-Miranda, Virginia Sanchez-Monroy, Raul Jacobo Delgado-Macuil, David Guillermo Perez-Ishiwara, Marlon Rojas-Lopez
Some of the greatest challenges in stem cells (SCs) biology and regenerative medicine are differentiation control of SCs and ensuring the purity of differentiated cells. In this work, we differentiated mouse pluripotent stem cells (mPSCs) toward pancreatic cells characterizing this differentiation process by molecular and spectroscopic technics. Both mPSCs and Differentiated Pancreatic Cells (DPCs) were subjected to a genetic, phenotypic, and biochemical analysis by real-time quantitative PCR (RT-qPCR), immunocytochemistry, and Fourier Transform Infrared (FTIR) spectroscopy...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27569862/differentiation-of-human-foreskin-fibroblast-derived-induced-pluripotent-stem-cells-into-hepatocyte-like-cells
#17
Jianjun Wang, Ping Zhao, Zhihong Wan, Xueyuan Jin, Yongqian Cheng, Tao Yan, Song Qing, Ning Ding, Shaojie Xin
: The aim of this study was to investigate the differentiation potential of induced pluripotent stem cells (iPSCs) derived from human foreskin fibroblasts (HFFs) into hepatocyte-like cells (HLCs). The iPSCs were firstly induced by transduction of OCT4, SOX2, KLF4, and c-MYC into HFFs using retrovirus. Afterwards, expressions of pluripotency factors were identified by semiquantitative reverse transcription-polymerase chain reaction and immunofluorescence staining, and karyotype, embryoid, and teratoma were observed by microscope...
October 2016: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27528602/soxf-transcription-factors-are-positive-feedback-regulators-of-vegf-signaling
#18
Kangsan Kim, Il-Kug Kim, Jee Myung Yang, Eunhyeong Lee, Bong Ihn Koh, Sukhyun Song, Junseong Park, Sungsu Lee, Chulhee Choi, Jin Woo Kim, Yoshiaki Kubota, Gou Young Koh, Injune Kim
RATIONALE: Vascular endothelial growth factor (VEGF) signaling is a key pathway for angiogenesis and requires highly coordinated regulation. Although the Notch pathway-mediated suppression of excessive VEGF activity via negative feedback is well known, the positive feedback control for augmenting VEGF signaling remains poorly understood. Transcription factor Sox17 is indispensable for angiogenesis, but its association with VEGF signaling is largely unknown. The contribution of other Sox members to angiogenesis also remains to be determined...
September 16, 2016: Circulation Research
https://www.readbyqxmd.com/read/27521520/molecular-basis-for-the-genome-engagement-by-sox-proteins
#19
Linlin Hou, Yogesh Srivastava, Ralf Jauch
The Sox transcription factor family consists of 20 members in the human genome. Many of them are key determinants of cellular identities and possess the capacity to reprogram cell fates by pioneering the epigenetic remodeling of the genome. This activity is intimately tied to their ability to specifically bind and bend DNA alone or with other proteins. Here we discuss our current knowledge on how Sox transcription factors such as Sox2, Sox17, Sox18 and Sox9 'read' the genome to find and regulate their target genes and highlight the roles of partner factors including Pax6, Nanog, Oct4 and Brn2...
August 10, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27513557/5-azacytidine-suppresses-ec9706-cell-proliferation-and-metastasis-by-upregulating-the-expression-of-sox17-and-cdh1
#20
Wenli Li, Dan Wu, Ziyu Niu, Dalei Jiang, Huan Ma, Heming He, Xiuli Zuo, Xiangjun Xie, Yuanlong He
5-Azacytidine is a well-known anticancer drug that is clinically used in the treatment of breast cancer, melanoma and colon cancer. It has been reported that 5-azacytidine suppresses the biological behavior of esophageal cancer cells. However, corresponding mechanisms remain unclear. In this study, using Transwell invasion and cell proliferation assays, we demonstrated that 5-azacytidine significantly inhibited the metastasis and proliferation of EC9706 cells, and upregulated the expression of cadherin 1 (CDH1) and SRY-box containing gene 17 (SOX17)...
October 2016: International Journal of Molecular Medicine
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