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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
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
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
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
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
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 6, 2016: Developmental Cell
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
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
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
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
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
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
C Parisi, S Mastoraki, A Markou, A Strati, M Chimonidou, V Georgoulias, E S Lianidou
BACKGROUND: Liquid biopsy is based on minimally invasive blood tests and has the potential to characterize the evolution of a solid tumor in real time, by extracting molecular information from circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Epigenetic silencing of tumor and metastasis suppressor genes plays a key role in survival and metastatic potential of cancer cells. Our group was the first to show the presence of epigenetic alterations in CTCs. METHODS: We present the development and analytical validation of a highly specific and sensitive Multiplex Methylation Specific PCR-coupled liquid bead array (MMSPA) for the simultaneous detection of the methylation status of three tumor and metastasis suppressor genes (CST6, SOX17 and BRMS1) in liquid biopsy material (CTCs, corresponding ctDNA) and paired primary breast tumors...
October 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Andrew J Lilly, Georges Lacaud, Valerie Kouskoff
Cardiovascular development during embryogenesis involves complex changes in gene regulatory networks regulated by a variety of transcription factors. In this review we discuss the various reported roles of the SOXF factors: SOX7, SOX17 and SOX18 in cardiac, vascular and lymphatic development. SOXF factors have pleiotropic roles during these processes, and there is significant redundancy and functional compensation between SOXF family members. Despite this, evidence suggests that there is some specificity in the transcriptional programs they regulate which is necessary to control the differentiation and behaviour of endothelial subpopulations...
July 25, 2016: Seminars in Cell & Developmental Biology
Zibo Li, Xinwu Guo, Lili Tang, Limin Peng, Ming Chen, Xipeng Luo, Shouman Wang, Zhi Xiao, Zhongping Deng, Lizhong Dai, Kun Xia, Jun Wang
Circulating cell-free DNA (cfDNA) has been considered as a potential biomarker for non-invasive cancer detection. To evaluate the methylation levels of six candidate genes (EGFR, GREM1, PDGFRB, PPM1E, SOX17, and WRN) in plasma cfDNA as biomarkers for breast cancer early detection, quantitative analysis of the promoter methylation of these genes from 86 breast cancer patients and 67 healthy controls was performed by using microfluidic-PCR-based target enrichment and next-generation bisulfite sequencing technology...
July 23, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Stephanie Bonney, Susan Harrison-Uy, Swati Mishra, Amber M MacPherson, Youngshik Choe, Dan Li, Shou-Ching Jaminet, Marcus Fruttiger, Samuel J Pleasure, Julie A Siegenthaler
UNLABELLED: As neural structures grow in size and increase metabolic demand, the CNS vasculature undergoes extensive growth, remodeling, and maturation. Signals from neural tissue act on endothelial cells to stimulate blood vessel ingression, vessel patterning, and acquisition of mature brain vascular traits, most notably the blood-brain barrier. Using mouse genetic and in vitro approaches, we identified retinoic acid (RA) as an important regulator of brain vascular development via non-cell-autonomous and cell-autonomous regulation of endothelial WNT signaling...
July 20, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Daniel Nettersheim, Isabell Arndt, Rakesh Sharma, Stefanie Riesenberg, Sina Jostes, Simon Schneider, Michael Hölzel, Glen Kristiansen, Hubert Schorle
BACKGROUND: Cancer/testis-antigens (CTAs) are specifically expressed in human malignancies and testis tissue, but their molecular functions are poorly understood. CTAs serve as regulators of gene expression, cell cycle and spermatogenesis, as well as targets for immune-based therapies. The CTA PRAME is expressed in various cancers, antagonises retinoic acid signalling and is regulated by DNA methylation and histone acetylation. METHODS: We analysed the molecular function of the CTA PRAME in primordial germ cells (PGC) and testicular germ cell cancers (GCC)...
August 9, 2016: British Journal of Cancer
Sara Cuvertino, Georges Lacaud, Valerie Kouskoff
During embryogenesis, the three SOXF transcription factors, SOX7, SOX17 and SOX18, regulate the specification of the cardiovascular system and are also involved in the development of haematopoiesis. The ectopic expression of SOX17 in both embryonic and adult blood cells enhances self-renewal. Likewise, the enforced expression of SOX7 during embryonic development promotes the proliferation of early blood progenitors and blocks lineage commitment. However, whether SOX7 expression can also affect the self-renewal of adult blood progenitors has never been explored...
July 2016: Open Biology
Keisuke Sako, Saurabh J Pradhan, Vanessa Barone, Álvaro Inglés-Prieto, Patrick Müller, Verena Ruprecht, Daniel Čapek, Sanjeev Galande, Harald Janovjak, Carl-Philipp Heisenberg
During metazoan development, the temporal pattern of morphogen signaling is critical for organizing cell fates in space and time. Yet, tools for temporally controlling morphogen signaling within the embryo are still scarce. Here, we developed a photoactivatable Nodal receptor to determine how the temporal pattern of Nodal signaling affects cell fate specification during zebrafish gastrulation. By using this receptor to manipulate the duration of Nodal signaling in vivo by light, we show that extended Nodal signaling within the organizer promotes prechordal plate specification and suppresses endoderm differentiation...
July 19, 2016: Cell Reports
Mohammad Kazemi Ashtiani, Mojgan Zandi, Jalal Barzin, Yaser Tahamtani, Mohammad Hossein Ghanian, Azadeh Moradmand, Morteza Ehsani, Hossein Nezari, Mehran Rezaei Larijani, Hossein Baharvand
Human embryonic stem cell (hESC)-derived endodermal cells are of interest for the development of cellular therapies to treat disorders such as liver failure. The soluble form of activin A (Act) has been widely used as an in vitro inducer of definitive endoderm (DE). In this study, we have developed a nanofibrous poly (ɛ-caprolactone) substrate, biofunctionalized with Act, for directed differentiation of hESCs into DE. Bioconjugation of Act on nanofibrous meshes was confirmed by enzyme-linked immunosorbent assay (ELISA) and immunostaining...
November 2016: Journal of Biomedical Materials Research. Part A
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