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https://www.readbyqxmd.com/read/28813671/oct4-and-sox2-work-as-transcriptional-activators-in-reprogramming-human-fibroblasts
#1
Santosh Narayan, Gene Bryant, Shivangi Shah, Georgina Berrozpe, Mark Ptashne
SOX2 and OCT4, in conjunction with KLF4 and cMYC, are sufficient to reprogram human fibroblasts to induced pluripotent stem cells (iPSCs), but it is unclear if they function as transcriptional activators or as repressors. We now show that, like OCT4, SOX2 functions as a transcriptional activator. We substituted SOX2-VP16 (a strong activator) for wild-type (WT) SOX2, and we saw an increase in the efficiency and rate of reprogramming, whereas the SOX2-HP1 fusion (a strong repressor) eliminated reprogramming...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28809024/chicken-induced-pluripotent-stem-cells-establishment-and-characterization
#2
Aurelie Fuet, Bertrand Pain
In mammals, the introduction of the OSKM (Oct4, Sox2, Klf4, and c-Myc) genes into somatic cells has allowed generating induced pluripotent stem (iPS) cells. So far, this process has been only clearly demonstrated in mammals. Here, using chicken as an avian model, we describe a set of protocols allowing the establishment, characterization, maintenance, differentiation, and injection of putative reprogrammed chicken Induced Pluripotent Stem (iPS) cells.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28807898/hypothalamic-sonic-hedgehog-is-required-for-cell-specification-and-proliferation-of-lhx3-lhx4-pituitary-embryonic-precursors
#3
G Carreno, J Apps, E J Lodge, L Panousopoulos, S Haston, J M Gonzalez-Meljem, H Hahn, C L Andoniadou, J P Martinez-Barbera
Sonic hedgehog (SHH) is an essential morphogenetic signal dictating cell fate decisions in several developing organs in mammals. In vitro data suggest that SHH is required to specify LHX3+/LHX4+ Rathke's pouch (RP) progenitor identity. However, in vivo studies have failed to reveal such a function, supporting instead, a critical role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3+/LHX4+ RP identity in mouse embryos...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28806395/rad6-promotes-dna-repair-and-stem-cell-signaling-in-ovarian-cancer-and-is-a-promising-therapeutic-target-to-prevent-and-treat-acquired-chemoresistance
#4
R R Somasagara, S M Spencer, K Tripathi, D W Clark, C Mani, L Madeira da Silva, J Scalici, H Kothayer, A D Westwell, R P Rocconi, K Palle
Ovarian cancer (OC) is the most deadly gynecological cancer and unlike most other neoplasms, survival rates for OC have not significantly improved in recent decades. We show that RAD6, an ubiquitin-conjugating enzyme, is significantly overexpressed in ovarian tumors and its expression increases in response to carboplatin chemotherapy. RAD6 expression correlated strongly with acquired chemoresistance and malignant behavior of OC cells, expression of stem cell genes and poor prognosis of OC patients, suggesting an important role for RAD6 in ovarian tumor progression...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28803914/targeted-disruption-of-tcf12-reveals-heb-as-essential-in-human-mesodermal-specification-and-hematopoiesis
#5
Yang Li, Patrick M Brauer, Jastaranpreet Singh, Sintia Xhiku, Kogulan Yoganathan, Juan Carlos Zúñiga-Pflücker, Michele K Anderson
Hematopoietic stem cells arise from mesoderm-derived hemogenic endothelium (HE) during embryogenesis in a process termed endothelial-hematopoietic transition (EHT). To better understand the gene networks that control this process, we investigated the role of the transcription factor HEB (TCF12) by disrupting the TCF12 gene locus in human embryonic stem cells (hESCs) and inducing them to differentiate toward hematopoietic outcomes. HEB-deficient hESCs retained key features of pluripotency, including expression of SOX2 and SSEA-4 and teratoma formation, while NANOG expression was reduced...
August 2, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28802580/suppressive-role-of-ogt-mediated-o-glcnacylation-of-bap1-in-retinoic-acid-signaling
#6
Seungtae Moon, Yong-Kyu Lee, Sang-Wang Lee, Soo-Jong Um
BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). Here, we confirmed the physical interaction and investigated its functional significance. The O-GlcNAcylation of BAP1, which requires OGT, was examined in vivo and in vitro, and was proven using alloxan, an OGT inhibitor...
August 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28802012/the-inhibitory-effect-of-5-7-dmf-on-pancreatic-sphere-forming-cell-function-mediated-by-foxm1-gene-expression
#7
Deyu Zeng, Jian Ma, Rongrong Li, Jianfeng Yang, Xianli Yin
Pancreatic cancer is one of the major human malignant tumors severely endangering human health and life with high mortality due to the concealment of early symptoms and lack of effective therapies during advanced stages. The identification of pancreatic cancer stem cell functions has been as important strategy for understanding of pancreatic cancer biology and novel drug and therapy development. In the present study, we successfully isolated the pancreatic sphere-forming cells from pancreatic cancer cell line PANC-1 by sphere-forming method and we found that the sphere-forming ability and the cell migration rate of pancreatic sphere-forming cells were significantly inhibited by 5,7-DMF treatment, which was supported by the corresponding changes of several EMT biomarkers after being treated with 5,7-DMF...
August 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28798691/fentanyl-promotes-breast-cancer-cell-stemness-and-epithelial-mesenchymal-transition-by-upregulating-%C3%AE-1-6-fucosylation-via-wnt-%C3%AE-catenin-signaling-pathway
#8
Hong-Fang Yang, Ming Yu, Hui-Dan Jin, Jia-Qi Yao, Zhi-Li Lu, Iddrisu B Yabasin, Qiu Yan, Qing-Ping Wen
Cancer pain is a common and severe complication of human breast cancer, and relieving pain is fundamental strategy in the treatment. Fentanyl, as an opioid analgesic, is widely used in breast cancer patients. However, little is known about its effects on stemness and epithelial-mesenchymal transition (EMT) of breast cancer cells. Aberrant protein glycosylation is involved in cancer malignancy. The α1, 6-fucosylation is an important type of glycosylation, and the elevated α1, 6-fucosylation catalyzed by fucosyltransferase VIII (FUT8) is found in many tumors...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28795331/cells-expressing-prominin-1-in-neonatal-murine-inferior-colliculus-differentiate-into-neurons-and-glia
#9
Haruka Okazaki, Akira Kanda, Seiji Kanda, Takaki Shimono, Yasutaka Yun, Yoshiki Kobayashi, Zeyun Wang, Hisashi Ooka, Kensuke Suzuki, Dan Bui Van, Koichi Tomoda, Hiroshi Iwai, Toshimasa Nishiyama
Inferior colliculus (IC) is a major center for the integration and processing of acoustic information from ascending auditory pathways. Damage to the IC as well as normal aging can impair auditory function. Novel strategies such as stem cell (SC)-based regenerative therapy are required for functional recovery because mature neural cells have a minimal regenerative capacity after an injury. However, it is not known if there are neural stem cells (NSCs) in the IC. Herein, we screened for NSCs by surface marker analysis using flow cytometry...
August 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28795134/in-vivo-analysis-of-the-neurovascular-niche-in-the-developing-xenopus-brain
#10
Melissa Lau, Jianli Li, Hollis T Cline
The neurovascular niche is a specialized microenvironment formed by the interactions between neural progenitor cells (NPCs) and the vasculature. While it is thought to regulate adult neurogenesis by signaling through vascular-derived soluble cues or contacted-mediated cues, less is known about the neurovascular niche during development. In Xenopus laevis tadpole brain, NPCs line the ventricle and extend radial processes tipped with endfeet to the vascularized pial surface. Using in vivo labeling and time-lapse imaging in tadpoles, we find that intracardial injection of fluorescent tracers rapidly labels Sox2/3-expressing NPCs and that vascular-circulating molecules are endocytosed by NPC endfeet...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28794048/hepatitis-c-virus-core-protein-modulates-endoglin-cd105-signaling-pathway-for-liver-pathogenesis
#11
Young-Chan Kwon, Reina Sasaki, Keith Meyer, Ranjit Ray
Endoglin is part of the TGF-β receptor complex and has a crucial role in fibrogenesis and angiogenesis. It is also an important protein for tumor growth, survival, and cancer cell metastasis. In our previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition state (EMT) and cancer stem-like cell (CSC) properties in human hepatocytes. Our array data suggested that endoglin (CD105) mRNA is significantly upregulated in HCV associated CSCs. In this study, we have observed increased endoglin expression on the cell surface of HCV core expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28794006/identification-of-the-sox2-interactome-by-bioid-reveals-ep300-as-a-mediator-of-sox2-dependent-squamous-differentiation-and-lung-squamous-cell-carcinoma-growth
#12
Bo Ram Kim, Etienne Coyaud, Estelle Laurent, Jonathan St-Germain, Emily Van de Laar, Ming Sound Tsao, Brian Raught, Nadeem Moghal
Lung cancer is the leading cause of cancer mortality worldwide, with squamous cell carcinoma (SQCC) being the second most common form. SQCCs are thought to originate in bronchial basal cells through an injury response to smoking, which results in this stem cell population committing to hyperplastic squamous rather than mucinous and ciliated fates. Copy number gains in SOX2 in the region of 3q26-28 occur in 94% of SQCCs, and appear to act both early and late in disease progression by stabilizing the initial squamous injury response in stem cells and promoting growth of invasive carcinoma...
August 9, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28793245/sox2-is-a-marker-for-stem-like-tumor-cells-in-bladder-cancer
#13
Fengyu Zhu, Weiqing Qian, Haojie Zhang, Yu Liang, Mingqing Wu, Yingyin Zhang, Xiuhong Zhang, Qian Gao, Yang Li
It has been reported that functionally distinct cancer stem cells (CSCs) exist in human bladder cancer (BCa). Here, we found that Sox2, a transcription factor that is well characterized as a marker for stem cells, is upregulated in both mouse and human BCa. Sox2 expression is absent in normal urothelial cells, but it begins to be expressed in pre-neoplastic bladder tumors and continues to be expressed in invasive mouse BCa. Using s as a reporter of Sox2 transcriptional expression, we demonstrated that Sox2-expressing cells mark a subpopulation of tumor cells that fuel the growth of established BCa...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28778071/suppression-of-pancreatic-adenocarcinoma-upregulated-factor-pauf-increases-the-sensitivity-of-pancreatic-cancer-to-gemcitabine-and-5fu-and-inhibits-the-formation-of-pancreatic-cancer-stem-like-cells
#14
Jae Hee Cho, Sun A Kim, Soo Been Park, Hee Man Kim, Si Young Song
Pancreatic cancer stem cells (CSCs) play a crucial role in tumorigenesis and chemoresistance of pancreatic ductal adenocarcinoma. Pancreatic adenocarcinoma up-regulated factor (PAUF), a novel secretory protein, has been shown to contribute to cancer progression and metastasis. Because the clinical relationship between PAUF and pancreatic CSCs is largely unknown, we investigated the associations between the functional role of PAUF and pancreatic CSCs. Pancreatic cancer sphere cultured from the CFPAC-1 cells showed elevated expression of PAUF and pluripotent stemness genes (Oct4, Nanog, Stat3, and Sox2), and the mRNA of PAUF were increased in CD44+CD24+ESA+ pancreatic CSCs...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28776863/artificial-acceleration-of-mammalian-cell-reprogramming-by-bacterial-proteins
#15
Takashi Ikeda, Ikuo Uchiyama, Mio Iwasaki, Tetsuhiko Sasaki, Masato Nakagawa, Keisuke Okita, Shinji Masui
The molecular mechanisms of cell reprogramming and differentiation involve various signaling factors. Small molecule compounds have been identified to artificially influence these factors through interacting cellular proteins. Although such small molecule compounds are useful to enhance reprogramming and differentiation and to show the mechanisms that underlie these events, the screening usually requires a large number of compounds to identify only a very small number of hits (e.g., one hit among several tens of thousands of compounds)...
August 4, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28774835/current-and-emerging-biomarkers-in-tumors-of-the-central-nervous-system-possible-diagnostic-prognostic-and-therapeutic-applications
#16
REVIEW
Ishaq N Khan, Najeeb Ullah, Deema Hussein, Kulvinder S Saini
Recent investments in research associated with the discovery of specific tumor biomarkers important for efficient diagnosis and prognosis of the patients are beginning to bear fruit. Key biomarkers could potentially outweigh traditional radiological or pathological methods by enabling specificity of early detection, when coupled with tumor molecular profiling and clinical associations. Only few biomarkers are approved by regulatory authorities for Central Nervous System Tumors (CNSTs), despite the evaluation of a large number of CNST related markers during clinical trials...
July 31, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28768706/the-prevalence-of-cancer-associated-autoantibodies-in-patients-with-gastric-cancer-and-progressive-grades-of-premalignant-lesions
#17
Irēna Meistere, Simone Werner, Pawel Zayakin, Karīna Siliņa, Undīne Rulle, Angelina Pismennaja, Daiga Šantare, Ilze Kikuste, Sergejs Isajevs, Marcis Leja, Limas Kupčinskas, Juozas Kupčinskas, Laimas Jonaitis, Chun-Ying Wu, Hermann Brenner, Aija Linē, Zane Kalniņa
BACKGROUND: Serum autoantibodies against tumor-associated antigens (TAA) are detectable in early stage gastric cancer patients; however, the time point during cancerogenesis when they appear in circulation is still obscure. METHODS: In this study, we developed a recombinant antigen microarray and analyzed the prevalence of autoantibodies against 102 TAAs in 829 gastric cancer patients and 929 healthy controls from Caucasian and Asian populations, as well as 100 patients with chronic atrophic gastritis and 775 individuals staged according to different grades of intestinal metaplasia...
August 2, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28765173/a2a-adenosine-receptors-control-pancreatic-dysfunction-in-high-fat-diet-induced-obesity
#18
Balázs Csóka, Gábor Törő, Joana Vindeirinho, Zoltán V Varga, Balázs Koscsó, Zoltán H Németh, Endre Kókai, Luca Antonioli, Mara Suleiman, Piero Marchetti, Karolina Cseri, Ádám Deák, László Virág, Pál Pacher, Péter Bai, György Haskó
Adenosine, a key extracellular signaling mediator, regulates several aspects of metabolism by activating 4 G protein-coupled receptors, the A1, A2A, A2B, and A3 adenosine receptors (ARs). The role of A2AARs in regulating high-fat-diet (HFD)-induced metabolic derangements is unknown. To evaluate the role of A2AARs in regulating glucose and insulin homeostasis in obesity, we fed A2AAR knockout (KO) and control mice an HFD for 16 wk to initiate HFD-induced metabolic disorder. We found that genetic deletion of A2AARs caused impaired glucose tolerance in mice fed an HFD...
August 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28758191/il-27-signaling-induces-stem-cell-antigen-1-expression-in-t-lymphocytes-in-vivo
#19
Zhihao Liu, Lisha Wu, Jing Zhu, Xiaotong Zhu, Jianmin Zhu, Jin-Qing Liu, Jianchao Zhang, Jonathan P Davis, Sanjay Varikuti, Abhay R Satoskar, Jie Zhou, Ming-Song Li, Xue-Feng Bai
Stem cell antigen-1 (Sca-1/Ly6A/E) is a cell surface glycoprotein that is often used as a biomarker for stem cells and cell stemness. However, it is not clear what factors can directly induce the expression of Sca-1/Ly6A/E in T lymphocytes in vivo, and if induction of Sca-1 is associated with T cell stemness. In this study, we show that IL-27, a member of the IL-12 family of cytokines, directly induces Sca-1 expression in T cells in vivo. We found that mice-deficient for IL-27 (either P28 or EBI3) or its signaling (IL-27Rα) had profound reduction of Sca-1 expression in naïve (CD62L(+) CD44(-) ), memory (CD62L(+) CD44(+) ) and effector (CD62L(-) CD44(+) ) T cells...
July 31, 2017: Immunology
https://www.readbyqxmd.com/read/28753574/functional-characterization-of-lysine-specific-demethylase-2-lsd2-kdm1b-in-breast-cancer-progression
#20
Lin Chen, Shauna N Vasilatos, Ye Qin, Tiffany A Katz, Chunyu Cao, Hao Wu, Nilgun Tasdemir, Kevin M Levine, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Flavin-dependent histone demethylases govern histone H3K4 methylation and act as important chromatin modulators that are extensively involved in regulation of DNA replication, gene transcription, DNA repair, and heterochromatin gene silencing. While the activities of lysine-specific demethylase 1 (LSD1/KDM1A) in facilitating breast cancer progression have been well characterized, the roles of its homolog LSD2 (KDM1B) in breast oncogenesis are relatively less understood. In this study, we showed that LSD2 protein level was significantly elevated in malignant breast cell lines compared with normal breast epithelial cell line...
July 19, 2017: Oncotarget
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