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Yi-Chao Hsu, Yu-Ting Wu, Chia-Ling Tsai, Yau-Huei Wei
In mammalian cells, there are seven members of the sirtuin protein family (SIRT1-7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a-SIRT1-p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells...
March 2018: Experimental Biology and Medicine
Jiao Ji, Yan Yu, Zhi-Ling Li, Ming-Yuan Chen, Rong Deng, Xiang Huang, Guang-Feng Wang, Meng-Xia Zhang, Qi Yang, Senthilkumar Ravichandran, Gong-Kan Feng, Xue-Lian Xu, Chen-Lu Yang, Miao-Zhen Qiu, Lin Jiao, Dajun Yang, Xiao-Feng Zhu
Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties...
2018: Theranostics
Stephen Keysar, Justin Eagles, Bettina Miller, Brian C Jackson, Farshad N Chowdhury, Julie Reisinger, Tugs-Saikhan Chimed, Phuong N Le, J Jason Morton, Hilary Somerset, Marileila Varella-Garcia, Aik-Choon Tan, John I Song, Daniel W Bowles, Mary E Reyland, Antonio Jimeno
PURPOSE: Salivary gland cancers (SGC) frequently present with distant metastases many years after diagnosis, suggesting a cancer stem cell (CSC) subpopulation that initiates late recurrences; however current models are limited both in their availability and suitability to characterize these rare cells. EXPERIMENTAL DESIGN: Patient-derived xenografts (PDX) were generated by engrafting patient tissue onto nude mice from one acinic cell carcinoma (AciCC), four adenoid cystic carcinoma (ACC), and three mucoepidermoid carcinoma (MEC) cases, which were derived from successive relapses from the same MEC patient...
March 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Aarne Fleischer, Iván M Lorenzo, Esther Palomino, Trond Aasen, Fernando Gómez, Miguel Servera, Víctor J Asensio, Víctor Gálvez, Juan Carlos Izpisúa-Belmonte, Daniel Bachiller
Cystic Fibrosis (CF) is a monogenic, lethal disease caused by mutations in the cystic fibrosis transmembrane conductance (CFTR) gene. Here we report the production of CF-iPS cell lines from two different p.F508del homozygous female patients (Table 1). Two different primary cell types, skin fibroblasts and keratinocytes, were transfected with retroviral cocktails containing four: c-MYC, KLF4, OCT4 and SOX2 (MKOS) or three: KLF4, OCT4 and SOX2 (KOS) reprogramming factors. Two fibroblast-derived MKOS lines are described in the main text...
March 11, 2018: Stem Cell Research
Patrick J Atkinson, Yaodong Dong, Shuping Gu, Wenwen Liu, Elvis Huarcaya Najarro, Tomokatsu Udagawa, Alan G Cheng
During development, Sox2 is indispensable for cell division and differentiation, yet its roles in regenerating tissues are less clear. Here, we used combinations of transgenic mouse models to reveal that Sox2 haploinsufficiency (Sox2haplo) increases rather than impairs cochlear regeneration in vivo. Sox2haplo cochleae had delayed terminal mitosis and ectopic sensory cells, yet normal auditory function. Sox2haplo amplified and expanded domains of damage-induced Atoh1+ transitional cell formation in neonatal cochlea...
March 19, 2018: Journal of Clinical Investigation
Rinat Sultanov, Olga Lebedeva, Georgij Arapidi, Maria Lagarkova, Sergei Kiselev
The genetic reprogramming technology allows generation of induced pluripotent stem cells (iPSCs) from somatic cells (Takahashi and Yamanaka, 2006) [1]. iPSCs have the ability to self-renew, and to differentiate into any type of somatic cells, and are considered as a promising tool for drug development, disease modeling, and regenerative medicine. The reprogramming factors (oct4, sox2, klf4, c-myc) can be delivered to the cell nucleus either by vectors integrating into the genome (lentiviruses, retroviruses) or by non-integrative methods (e...
April 2018: Data in Brief
Weiwei Chen, Jiajia An, Jiwei Guo, Yan Wu, Lijuan Yang, Juanjuan Dai, Kaikai Gong, Shuang Miao, Sichuan Xi, Jing Du
PURPOSE: Sodium selenite (SS) has been widely reported to induce apoptosis in various cancer cell types. However, the underlying molecular mechanisms governing SS-mediated repression of lung cancer stem cells remain largely undefined. METHODS: In vitro assays of cell proliferation, clonal formation, apoptosis, migration and cancer stemness cell sphere formation were performed to examine the inhibitory effects of SS on lung adenocarcinoma (LAD) cells with or without the overexpression of SRY-related high-mobility-group box 2 (SOX2)...
March 15, 2018: Cancer Chemotherapy and Pharmacology
Tingchao Mao, Chengquan Han, Ruizhi Deng, Biao Wei, Peng Meng, Yan Luo, Yong Zhang
Epigenetic modifications extensively occur in mammalian embryonic development and cell differentiation process. They play an essential role in the reprogramming of nuclei during somatic cell nuclear transfer (SCNT) and subsequent in vitro embryonic development. Recently, SCNT embryos have been verified to contain a subnormal level of histone H3K4 dimethylation (H3K4me2) in contrast to in vitro fertilized embryos. This finding suggested that increasing H3K4me2 levels may ameliorate the aberrant development of cloned embryos...
March 15, 2018: Systems Biology in Reproductive Medicine
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
Tulika Mitra, Parash Prasad, Pritha Mukherjee, Susri Ray Chaudhuri, Urmi Chatterji, Sib S Roy
Ovarian cancer (OC) is the fourth most common gynecological malignancy due to its highly aggressive, recurrent, and drug-resistant nature. The last two features are rendered by the presence of cancer stem cells (CSCs). Factors like TGFβ1 and their downstream signaling pathways are upregulated in most cancers and are known to induce EMT and stemness, but the exact mechanisms underlying the process remain unelucidated. In our study, TGFβ1 induced enhanced stem-like properties like high expression of the pluripotent markers SOX2, OCT4a, and NANOG, along with CD44, and CD117 in the OC cells...
March 14, 2018: Journal of Cellular Biochemistry
Jia-Ming Zhang, Kai Wei, Ming Jiang
BACKGROUND: Octamer-binding transcription factor 4 (OCT4) and SRY (sex determining region Y)-box 2 (SOX2) are common biomarkers of cancer stem cells, which contribute to the pathological processes of several carcinomas, while little is known about the effects of OCT4 and SOX2 on the prognosis of triple-negative breast cancer (TNBC). The purpose was to evaluate the correlation of tumor tissue OCT4 and SOX2 expressions with clinicopathological features and overall survival (OS) in surgical TNBC patients...
March 13, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Qiang Zhuang, Wenjuan Li, Christina Benda, Zhijian Huang, Tanveer Ahmed, Ping Liu, Xiangpeng Guo, David P Ibañez, Zhiwei Luo, Meng Zhang, Mazid Md Abdul, Zhongzhou Yang, Jiayin Yang, Yinghua Huang, Hui Zhang, Dehao Huang, Jianguo Zhou, Xiaofen Zhong, Xihua Zhu, Xiuling Fu, Wenxia Fan, Yulin Liu, Yan Xu, Carl Ward, Muhammad Jadoon Khan, Shahzina Kanwal, Bushra Mirza, Micky D Tortorella, Hung-Fat Tse, Jiayu Chen, Baoming Qin, Xichen Bao, Shaorong Gao, Andrew P Hutchins, Miguel A Esteban
Somatic cell reprogramming by exogenous factors requires cooperation with transcriptional co-activators and co-repressors to effectively remodel the epigenetic environment. How this interplay is regulated remains poorly understood. Here, we demonstrate that NCoR/SMRT co-repressors bind to pluripotency loci to create a barrier to reprogramming with the four Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC), and consequently, suppressing NCoR/SMRT significantly enhances reprogramming efficiency and kinetics. The core epigenetic subunit of the NCoR/SMRT complex, histone deacetylase 3 (HDAC3), contributes to the effects of NCoR/SMRT by inducing histone deacetylation at pluripotency loci...
March 12, 2018: Nature Cell Biology
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
Navroop K Dhaliwal, Kamelia Miri, Scott Davidson, Hala Tamim El Jarkass, Jennifer A Mitchell
Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation...
March 1, 2018: Stem Cell Reports
Hui Li, Ying Wang, Jiali Yang, Xiaoming Liu, Juan Shi
BACKGROUND: The incidence of lung cancer is gradually increased, and the cystic fibrosis transmembrane conductance regulator (CFTR) has recently demonstrated to have an implication in the deoncogenesis and malignant transformation of many types of cancers. The aim of this study is to investigate impacts of CFTR on the malignant features of lung adenocarcinoma A549 cells. METHODS: The capacity of cell proliferation, migration, invasion and clonogenicity of non-small cell lung cancer A549 cells were detected by CCK8 cell proliferation assay, cell scratch assay, Transwell cell invasion assay and clone formation assay, respectively...
February 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Yu Bin Lee, Eun Mi Kim, Hayeon Byun, Hyung-Kwan Chang, Kwanghee Jeong, Zachary M Aman, Yu Suk Choi, Jungyul Park, Heungsoo Shin
Numerous methods have been reported for the fabrication of 3D multi-cellular spheroids and their use in stem cell culture. Current methods typically relying on the self-assembly of trypsinized, suspended stem cells, however, show limitations with respect to cell viability, throughput, and accurate recapitulation of the natural microenvironment. In this study, we developed a new system for engineering cell spheroids by self-assembly of micro-scale monolayer of stem cells. We prepared synthetic hydrogels with the surface of chemically formed micropatterns (squares/circles with width/diameter of 200 μm) on which mesenchymal stem cells isolated from human nasal turbinate tissue (hTMSCs) were selectively attached and formed a monolayer...
March 1, 2018: Biomaterials
Charlotte Aaberg-Jessen, Mia D Sørensen, Ana L S A Matos, José M Moreira, Nils Brünner, Arnon Knudsen, Bjarne W Kristensen
BACKGROUND: We have previously identified tissue inhibitor of metalloproteinases-1 (TIMP-1) as a prognostic marker in glioblastomas. TIMP-1 has been associated with chemotherapy resistance, and CD63, a known TIMP-1-binding protein, has been suggested to be responsible for this effect. The aim of this study was to assess CD63 expression in astrocytomas focusing on the prognostic potential of CD63 alone and in combination with TIMP-1. METHODS: CD63 expression was investigated immunohistochemically in a cohort of 111 astrocytomas and correlated to tumor grade and overall survival by semi-quantitative scoring...
March 9, 2018: BMC Cancer
Nikos Schizas, N König, B Andersson, S Vasylovska, J Hoeber, E N Kozlova, N P Hailer
The acute phase of spinal cord injury is characterized by excitotoxic and inflammatory events that mediate extensive neuronal loss in the gray matter. Neural crest stem cells (NCSCs) can exert neuroprotective and anti-inflammatory effects that may be mediated by soluble factors. We therefore hypothesize that transplantation of NCSCs to acutely injured spinal cord slice cultures (SCSCs) can prevent neuronal loss after excitotoxic injury. NCSCs were applied onto SCSCs previously subjected to N-methyl-D-aspartate (NMDA)-induced injury...
March 7, 2018: Cell and Tissue Research
Yanfei Deng, Guiting Huang, Lingxiu Zou, Tianying Nong, Xiaoling Yang, Jiayu Cui, Yingming Wei, Sufang Yang, Deshun Shi
Amniotic mesenchymal stem cells (AMSCs) from livestock are valuable resources for animal reproduction and veterinary therapeutic. The purpose of this study is to explore a suitable way to isolate and culture the buffalo AMSCs (bAMSCs), and to identify their biological characteristics. Digestion with a combination of trypsin-EDTA and collagenase type I could obtain pure bAMSCs more effectively than trypsin-EDTA or collagenase type I alone. bAMSCs could proliferate steadily in vitro culture and exhibited fibroblastic-like morphology in vortex-shaped colony...
March 8, 2018: Journal of Veterinary Medical Science
Hassan Akrami, Behrouz Moradi, Diba Borzabadi Farahani, Kiumars Mehdizadeh
Nowadays, most studies focused on cancer stem cells (CSCs) through their abilities to cause tumorigenicity, drug resistance, and cancer recurrence. On the other side, nonsteroidal anti-inflammatory drugs (NSAIDs) have been taken into consideration because of cheapness and availability. For the reasons mentioned above, we have studied the effect of ibuprofen as an NSAID on CSCs derived from AGS and MKN-45 gastric cancer cell lines to perform effective cancer therapy. We evaluated cell viability, spheroid body formation, monolayer and soft agar colony formation to express the anti-cancer effect of ibuprofen on CSCs...
March 7, 2018: Cell Biology International
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