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https://www.readbyqxmd.com/read/29166607/kdm2b-regulates-somatic-reprogramming-through-variant-prc1-complex-dependent-function
#1
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/29163813/the-novel-zip4-regulation-and-its-role-in-ovarian-cancer
#2
Qipeng Fan, Qingchun Cai, Pengfei Li, Wenyan Wang, Jing Wang, Emily Gerry, Tian-Li Wang, Ie-Ming Shih, Kenneth P Nephew, Yan Xu
Our RNAseq analyses revealed that ZIP4 is a top gene up-regulated in more aggressive ovarian cancer cells. ZIP4's role in cancer stem cells has not been reported in any type of cancer. In addition, the role and regulation of ZIP4, a zinc transporter, have been studied in the context of extracellular zinc transporting. Factors other than zinc with ZIP4 regulatory effects are essentially unknown. ZIP4 expression and its regulation in epithelial ovarian cancer cells was assessed by immunoblotting, quantitative PCR, or immunohistochemistry staining in human ovarian tissues...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163026/generation-of-urine-cell-derived-non-integrative-human-ipscs-and-inscs-a-step-by-step-optimized-protocol
#3
Lin Cheng, Qiannan Lei, Chen Yin, Hui-Yun Wang, Kangxin Jin, Mengqing Xiang
Objective: Establishing a practical procedure to generate induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs) from human urine cells (UCs). In this report, we optimized a non-integrative protocol to generate patient-specific iPSC and iNSC lines with high reprogramming efficiency. Methods: UCs were electroporated with the pEP4-EO2S-ET2K and pEP4-M2L plasmids containing the OCT4, SOX2, KLF4, SV40LT, c-MYC, and LIN28 genes, and then cultured with N2B27 medium plus four small molecule compounds (A83-01, PD0325901, Thiazovivin, and CHIR99021)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29162985/cbfa2t2-is-associated-with-a-cancer-stem-cell-state-in-renal-cell-carcinoma
#4
Du-Chu Chen, You-De Liang, Liang Peng, Yi-Ze Wang, Chun-Zhi Ai, Xin-Xing Zhu, Ya-Wei Yan, Yasmeen Saeed, Bin Yu, Jingying Huang, Yuxin Gao, Jiaqi Liu, Yi-Zhou Jiang, Min Liu, Demeng Chen
Background: Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80-90% of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. Methods: OncoLnc was used as a tool for interactively exploring survival correlations. Gene manipulation and expression analysis were carried out using siRNA, RT-PCR and Western blotting...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29162538/metformin-promotes-the-proliferation-and-differentiation-of-murine-preosteoblast-by-regulating-the-expression-of-sirt6-and-oct4
#5
Wei Mu, Zhuoran Wang, Chuanyu Ma, Yunyun Jiang, Nannan Zhang, Kaiqiang Hu, Liyuan Li, Zhao Wang
Osteopenia, osteoporosis and bone salt metabolism disorder are common diseases in the aged and diabetics. From case reports of patients with T2DM, we have observed that metformin can decrease risk of bone fracture and promote bone formation. However, the underlying mechanism of metformin's effect on bone metabolism remains unknown. In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis. Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast...
November 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29162325/scriptaid-improves-the-reprogramming-of-donor-cells-and-enhances-canine-porcine-interspecies-embryo-development
#6
Jin-Gu No, Tai-Young Hur, Minghui Zhao, Seunghoon Lee, Mi-Kyung Choi, Yoon-Seok Nam, Dong-Hyun Yeom, Gi-Sun Im, Dong-Hoon Kim
Histone methylation, histone acetylation, and DNA methylation are the important factors for somatic cell nuclear transfer (SCNT). Histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have been used to improve cloning efficiency. In particular, scriptaid, an HDACi, has been shown to improve SCNT efficiency. However, no studies have been performed on canines. Here, we evaluated the effects of scriptaid on histone modification in canine ear fibroblasts (cEFs) and cloned canine embryos derived from cEFs...
November 18, 2017: Reproductive Biology
https://www.readbyqxmd.com/read/29162051/in-vitro-characterization-of-cd133-lo-cancer-stem-cells-in-retinoblastoma-y79-cell-line
#7
Rohini M Nair, Murali Ms Balla, Imran Khan, Ravi Kiran Reddy Kalathur, Paturu Kondaiah, Geeta K Vemuganti
BACKGROUND: Retinoblastoma (Rb), the most common childhood intraocular malignant tumor, is reported to have cancer stem cells (CSCs) similar to other tumors. Our previous investigation in primary tumors identified the small sized cells with low CD133 (Prominin-1) and high CD44 (Hyaluronic acid receptor) expression to be putative Rb CSCs using flow cytometry (FSC(lo)/SSC(lo)/CD133(lo)/CD44(hi)). With this preliminary data, we have now utilized a comprehensive approach of in vitro characterization of Y79 Rb cell line following CSC enrichment using CD133 surface marker and subsequent validation to confirm the functional properties of CSCs...
November 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29161957/induced-pluripotent-stem-cells-from-a-marsupial-the-tasmanian-devil-sarcophilus-harrisii-insight-into-the-evolution-of-mammalian-pluripotency
#8
Prasanna Weeratunga, Arash Shahsavari, Dmitry A Ovchinnikov, Ernst Jurgen Wolvetang, Deanne Jeanette Whitworth
We demonstrate the generation of Tasmanian devil (Sarcophilus harrisii) induced pluripotent stem cells (DeviPSCs) from dermal fibroblasts by lentiviral delivery of human transcription factors. DeviPSCs display characteristic pluripotent stem cell colony morphology, with individual cells having a high nuclear to cytoplasmic ratio and alkaline phosphatase activity. DeviPSCs are leukemia inhibitory factor-dependent and have reactivated endogenous OCT4 (POU5F1), POU2 (POU5F3), SOX2, NANOG and DAX1 genes, retained a normal karyotype, and concurrently silenced exogenous human transgenes...
November 22, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29159771/cldn6-enhances-chemoresistance-to-adm-via-af-6-erks-pathway-in-tnbc-cell-line-mdamb231
#9
Minlan Yang, Yanru Li, Yang Ruan, Yan Lu, Dongjing Lin, Yinping Xie, Bing Dong, Qihua Dang, Chengshi Quan
Claudin-6 (CLDN6), a critical tight junction protein acting as a tumor suppressor in breast cancer, is also considered to be a stem cell marker. Triple-negative breast cancer (TNBC) is a subtype of claudin-low and stem cell-like breast cancer which is chemoresistant to multiple anti-cancer drugs. The aim of our study was to determine whether CLDN6 plays a role in chemoresistance of TNBC. We found that overexpression of CLDN6 in TNBC cell line MDAMB231 significantly inhibited cell growth, migration, and invasion...
November 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29155325/promoter-activity-and-regulation-of-the-pou5f1-homolog-from-a-teleost-nile-tilapia
#10
Wei Jing, Huang Xiaohuan, Fan Zhenhua, Yang Zhuo, Da Fan, Tao Wenjing, Zhou Linyan, Wang Deshou
Mammalian POU5F1 (also known as OCT4) is an essential transcription factor that induces and controls stemness in the inner cell mass and embryonic stem (ES) cells. Its expression results from intricate regulatory networks involving its 5' upstream DNA elements and numerous transcription factors. Pou5f3, the ortholog of POU5F1, has been identified in non-mammalians including fish. However, little is known about the molecular mechanisms controlling its expression up to date. Here we report the promoter activity and regulation of Nile tilapia (Oreochromis niloticus) pou5f3 (Onpou5f3) in fish early-stage embryos and ES cells...
November 16, 2017: Gene
https://www.readbyqxmd.com/read/29153991/serine-347-phosphorylation-by-jnks-negatively-regulates-oct4-protein-stability-in-mouse-embryonic-stem-cells
#11
Ki Beom Bae, Dong Hoon Yu, Kun Yeong Lee, Ke Yao, Joohyun Ryu, Do Young Lim, Tatyana A Zykova, Myoung Ok Kim, Ann M Bode, Zigang Dong
The POU transcription factor OCT4 is critical for maintaining the undifferentiated state of embryonic stem cells (ESCs) and generating induced pluripotent stem cells (iPSCs), but its precise mechanisms of action remain poorly understood. Here, we investigated the role of OCT4 phosphorylation in the biological functions of ESCs. We observed that c-Jun N-terminal kinases (JNKs) directly interacted with and phosphorylated OCT4 at serine 347, which inhibited the transcriptional activity of OCT4. Moreover, phosphorylation of OCT4 induced binding of FBXW8, which reduced OCT4 protein stability and enhanced its proteasomal degradation...
November 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29141367/-differentiation-of-induced-pluripotent-stem-cells-into-neural-stem-cells-induced-by-brain-derived-neurotrophic-factor-via-wnt-%C3%AE-catenin-and-extracellular-signal-regulated-kinase-mitogen-activated-protein-kinases-signal-pathway
#12
S Q Chen, M Huang, C L Liu, Y Y Shen, Q Cai, P J Wang
Objective: To investigate the mechanism of brain-derived neurotrophic factor (BDNF) promoting induced pluripotent stem cells (iPSCs) to differentiate into neural stem cells (NSCs) via Wnt/β-catenin and extracellular signal-regulated kinase/mitogen-activated protein kinases (ERK/MAPK) signal pathways. Methods: iPSCs were cultured and identified. The iPSCs were induced to differentiate into NSCs by BDNF and retinoic acid (RA). Nestin was detected by immunofluorescence and flow cytometry after iPSCs differentiated...
November 7, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29141221/chemotherapy-induced-depletion-of-oct4-positive-cancer-stem-cells-in-a-mouse-model-of-malignant-testicular-cancer
#13
Timothy M Pierpont, Amy M Lyndaker, Claire M Anderson, Qiming Jin, Elizabeth S Moore, Jamie L Roden, Alicia Braxton, Lina Bagepalli, Nandita Kataria, Hilary Zhaoxu Hu, Jason Garness, Matthew S Cook, Blanche Capel, Donald H Schlafer, Teresa Southard, Robert S Weiss
Testicular germ cell tumors (TGCTs) are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140111/purging-exhausted-virus-specific-cd8-t-cell-phenotypes-by-somatic-cell-reprogramming
#14
Joshua Chan, Patrick Y Kim, Emiko Kranz, Yoshiko Nagaoka, YooJin Lee, Jing Wen, Heidi J Elsaesser, Meng Qin, David G Brooks, Gene-Errol Ringpis, Irvin S Y Chen, Masakazu Kamata
Cytotoxic T cells are critical in controlling virus infections. However, continuous antigen stimulation and negative regulatory factors cause CD8 T cells to enter a dysfunctional state (T cell exhaustion), resulting in viral persistence. We hypothesized that the exhausted T cell state could be molecularly rejuvenated using a somatic cell reprogramming technology, which is technically able to convert any types of cells to induced pluripotent stem cells (iPSCs), to regenerate functional T cells capable of purging chronic infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29138277/coupling-shrna-screens-with-single-cell-rna-seq-identifies-a-dual-role-for-mtor-in-reprogramming-induced-senescence
#15
Marieke Aarts, Athena Georgilis, Meryam Beniazza, Patrizia Beolchi, Ana Banito, Thomas Carroll, Marizela Kulisic, Daniel F Kaemena, Gopuraja Dharmalingam, Nadine Martin, Wolf Reik, Johannes Zuber, Keisuke Kaji, Tamir Chandra, Jesús Gil
Expression of the transcription factors OCT4, SOX2, KLF4, and cMYC (OSKM) reprograms somatic cells into induced pluripotent stem cells (iPSCs). Reprogramming is a slow and inefficient process, suggesting the presence of safeguarding mechanisms that counteract cell fate conversion. One such mechanism is senescence. To identify modulators of reprogramming-induced senescence, we performed a genome-wide shRNA screen in primary human fibroblasts expressing OSKM. In the screen, we identified novel mediators of OSKM-induced senescence and validated previously implicated genes such as CDKN1A We developed an innovative approach that integrates single-cell RNA sequencing (scRNA-seq) with the shRNA screen to investigate the mechanism of action of the identified candidates...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29137267/tumacrophage-macrophages-transformed-into-tumor-stem-like-cells-by-virulent-genetic-material-from-tumor-cells
#16
Yizhuang Zhang, Na Zhou, Xiuyan Yu, Xuehui Zhang, Shanxin Li, Zhen Lei, Ruobi Hu, Hui Li, Yiqing Mao, Xi Wang, Jinshu Zhang, Yuan Li, Hongyan Guo, David M Irwin, Gang Niu, Huanran Tan
Tumor-associated macrophages are regarded as tumor-enhancers as they have key roles in the subversion of adaptive immunity and in inflammatory circuits that promote tumor progression. Here, we show that cancer cells can subvert macrophages yielding cells that have gained pro-tumor functions. When macrophages isolated from mice or humans are co-cultured with dead cancer cell line cells, induced to undergo apoptosis to mimic chemotherapy, up-regulation of pro-tumor gene expression was identified. Phagocytosis of apoptotic cancer cells by macrophages resulted in their transformation into tumor stem (initiating)-like cells, as indicated by the expression of epithelial markers (e...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135280/factors-affecting-mouse-somatic-cell-nuclear-reprogramming-by-rabbit-ooplasms
#17
Xia Huang, Lili Song, Zhiyan Zhan, Haihui Gu, Haizhong Feng, Yanxin Li
Successful development of interspecies somatic cell nuclear transfer (iSCNT) embryos depends on compatibilities between ooplasmic and nuclear components. However, the mechanisms by which the compatibilities are regulated are still unknown. In this study, using mouse Oct4-green fluorescent protein (GFP) cells as donors and rabbit oocytes as recipients, we show that Oct4 and other pluripotency related genes were reactivated in some of mouse-rabbit iSCNT embryos, which could also activate Oct4 promoter-driven GFP reporter gene expression...
November 14, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/29134714/identification-of-perivascular-and-stromal-mesenchymal-stem-progenitor-cells-in-porcine-endometrium
#18
J Wiater, M Niedziela, A Posmysz, K Wartalski, B Gajda, Z Smorąg, Z Rajfur, J Karasiński
Mammalian uterus contains a population of mesenchymal stem/progenitor cells that likely contribute to endometrial regeneration during each reproductive cycle. In human and mouse, they reside in perivascular, epithelial and stromal compartments of the endometrial functionalis and basalis. Here, we aimed to identify tissue resident cells expressing mesenchymal stem cell markers CD29, CD44, CD90, CD105, CD140b and CD146 in the porcine endometrium. We used single immunofluorescence and Western blotting. Each of these markers was detected in small cells surrounding endometrial blood vessels...
November 14, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/29131256/the-expression-of-oct4-and-its-clinical-significance-in-laryngeal-squamous-carcinoma-tissues
#19
H-Y Chen, X-L Han, R-G Wang, X-F Song, H-Z Zhang
OBJECTIVE: To investigate the expression of OCT4 and its clinical significance in laryngeal squamous carcinoma tissues. PATIENTS AND METHODS: Immunohistochemical staining was used to analyze the expression of OCT4 in 61 cases of laryngeal squamous carcinoma and 10 cases of the adjacent normal laryngeal tissues. RESULTS: The expression of OCT4 was not detected in normal laryngeal tissues, but could be detected in the nucleus of laryngeal carcinoma...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29125994/enhanced-human-somatic-cell-reprogramming-efficiency-by-fusion-of-the-myc-transactivation-domain-and-oct4
#20
Ling Wang, Delun Huang, Chang Huang, Yexuan Yin, Kaneha Vali, Ming Zhang, Young Tang
The development of human induced pluripotent stem cells (iPSCs) holds great promise for regenerative medicine. However the iPSC induction efficiency is still very low and with lengthy reprogramming process. We utilized the highly potent transactivation domain (TAD) of MYC protein to engineer the human OCT4 fusion proteins. Applying the MYC-TAD-OCT4 fusion proteins in mouse iPSC generation leads to shorter reprogramming dynamics, with earlier activation of pluripotent markers in reprogrammed cells than wild type OCT4 (wt-OCT4)...
October 26, 2017: Stem Cell Research
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