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https://www.readbyqxmd.com/read/28533192/in-vitro-effects-of-reprogramming-factors-on-the-expressions-of-pluripotent-genes-and-cd34-gene-in-human-acute-promyelocytic-leukemia-hl-60-cells
#1
Liang-Fang Zhu, Min Xiao, Yong-Quan Chen, Ling-Yan Wang, Xiao-Feng Luo, Xiao-Hong Yuan, Jin-Hua Ren, Zhi-Zhe Chen, Jian-Da Hu, Ting Yang
OBJECTIVE: Our study aims to explore the in vitro effects of reprogramming factors on the expressions of pluripotent genes and CD34 gene in HL-60 cells. METHODS: According to the construction of retroviral vector LV-OSCK of reprogramming factors (Oct-4, Sox2, Klf4, c-Myc), 293T cells were transfected to detect virus titer. The endogenous pluripotent genes (Oct4, SOX2, c-Myc and Klf4) and CD34 mRNA and protein expressions were detected by AP staining, immunofluorescence staining, qRT-PCR and flow cytometry...
May 19, 2017: Genomics
https://www.readbyqxmd.com/read/28529134/direct-reprogramming-epigenetics-and-cardiac-regeneration
#2
REVIEW
Shota Kurotsu, Takeshi Suzuki, Masaki Ieda
The discovery of induced pluripotent stem cells (iPSCs) has revolutionized regenerative medicine. Autologous iPSCs can be generated by introducing 4 stem cell-specific factors (Oct4, Sox2, Klf4, c-Myc) into fibroblasts. iPSCs can propagate indefinitely and differentiate into clinically important cell types including cardiomyocytes, in vitro. The iPSC-derived cardiomyocytes represent a promising source of cells for cell-based therapeutic approaches for cardiac regeneration. However, there are several challenges in the clinical application of iPSCs: tumorigenicity of immature cells, poor survival of the transplanted myocardial cells, and cost and efficacy of this therapeutic approach...
May 18, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28528696/reprogramming-of-dermal-fibroblasts-into-osteo-chondrogenic-cells-with-elevated-osteogenic-potency-by-defined-transcription-factors
#3
Yinxiang Wang, Ming-Hoi Wu, May Pui Lai Cheung, Mai Har Sham, Haruhiko Akiyama, Danny Chan, Kathryn S E Cheah, Martin Cheung
Recent studies using defined transcription factors to convert skin fibroblasts into chondrocytes have raised the question of whether osteo-chondroprogenitors expressing SOX9 and RUNX2 could also be generated during the course of the reprogramming process. Here, we demonstrated that doxycycline-inducible expression of reprogramming factors (KLF4 [K] and c-MYC [M]) for 6 days were sufficient to convert murine fibroblasts into SOX9(+)/RUNX2(+) cellular aggregates and together with SOX9 (S) promoted the conversion efficiency when cultured in a defined stem cell medium, mTeSR...
May 15, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28524086/dietary-green-pea-protects-against-dss-induced-colitis-in-mice-challenged-with-high-fat-diet
#4
Shima Bibi, Luís Fernando de Sousa Moraes, Noelle Lebow, Mei-Jun Zhu
Obesity is a risk factor for developing inflammatory bowel disease. Pea is unique with its high content of dietary fiber, polyphenolics, and glycoproteins, all of which are known to be health beneficial. We aimed to investigate the impact of green pea (GP) supplementation on the susceptibility of high-fat diet (HFD)-fed mice to dextran sulfate sodium (DSS)-induced colitis. Six-week-old C57BL/6J female mice were fed a 45% HFD or HFD supplemented with 10% GP. After 7-week dietary supplementation, colitis was induced by adding 2...
May 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28514649/widespread-mitotic-bookmarking-by-histone-marks-and-transcription-factors-in-pluripotent-stem-cells
#5
Yiyuan Liu, Bobbie Pelham-Webb, Dafne Campigli Di Giammartino, Jiexi Li, Daleum Kim, Katsuhiro Kita, Nestor Saiz, Vidur Garg, Ashley Doane, Paraskevi Giannakakou, Anna-Katerina Hadjantonakis, Olivier Elemento, Effie Apostolou
During mitosis, transcription is halted and many chromatin features are lost, posing a challenge for the continuity of cell identity, particularly in fast cycling stem cells, which constantly balance self-renewal with differentiation. Here we show that, in pluripotent stem cells, certain histone marks and stem cell regulators remain associated with specific genomic regions of mitotic chromatin, a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes are bookmarked by both H3K27ac and the master regulators OCT4, SOX2, and KLF4, while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a cell-type invariant manner...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28509990/transient-activation-of-reprogramming-transcription-factors-using-protein-transduction-facilitates-conversion-of-human-fibroblasts-toward-cardiomyocyte-like-cells
#6
Zaniar Ghazizadeh, Hassan Rassouli, Hananeh Fonoudi, Mehdi Alikhani, Mahmood Talkhabi, Amir Darbandi-Azar, Shuibing Chen, Hossein Baharvand, Nasser Aghdami, Ghasem Hosseini Salekdeh
Derivation of cardiomyocytes directly from patients' own fibroblasts could offer a new therapeutic approach for those with ischemic heart disease. An essential step toward clinical application is to establish safe conversion of human fibroblasts into a cardiac fate. Here we aimed to efficiently and safely generate cardiomyocytes from human fibroblasts by direct delivery of reprogramming recombinant cell permeant form of reprogramming proteins followed by cardio-inductive signals. Human fetal and adult fibroblasts were transiently exposed to transactivator of transcription-fused recombinant OCT4, SOX2, KLF4 and c-MYC for 2 weeks and then were directly differentiated toward protein-induced cardiomyocyte-like cells (p-iCLCs) in a cardiac fate niche, carried out by treatment with a set of cardiogenic small molecules (sequential treatment of Chir, and IWP-2, SB431542 and purmorphamine)...
May 16, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28503428/soluble-expression-of-recomb-inant-cmyc-klf4-oct4-and-sox2-proteins-in-bacteria-and-transduction-into-living-cells
#7
Guo-Dan Liu, Shi-Feng Zhou, Xu-Chen Ding, Chun-Lai Fang, Shu-Yong Mi, Xiang-Chun Gao, Qing Han
AIM: To develop a new method to produce recombinant reprogramming proteins, cMyc, Klf4, Oct4, and Sox2, in soluble format with low cost for the generation of induced pluripotent stem cells (iPSCs). METHODS: A short polypeptide sequence derived from the HIV trans-activator of transcription protein (TAT) and the nucleus localization signal (NLS) polypeptide were fused to the N terminus of the reprogramming proteins and they were constructed into pCold-SUMO vector which can extremely improve the solubility of recombinant proteins...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28490810/establishment-of-induced-pluripotent-stem-cells-from-normal-b-cells-and-inducing-aid-expression-in-their-differentiation-into-hematopoietic-progenitor-cells
#8
Fumihiko Kawamura, Makoto Inaki, Atsushi Katafuchi, Yu Abe, Naohiro Tsuyama, Yumiko Kurosu, Aki Yanagi, Mitsunori Higuchi, Satoshi Muto, Takumi Yamaura, Hiroyuki Suzuki, Hideyoshi Noji, Shinichi Suzuki, Mitsuaki A Yoshida, Megumi Sasatani, Kenji Kamiya, Masafumi Onodera, Akira Sakai
B cell derived induced pluripotent stem cells (BiPSCs) were recently established from peripheral blood B cells by the simultaneous transfection of Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) and C/EBPα using a Sendai virus vector. Here, using a different method, we established BiPSCs with immunoglobulin heavy chain (IgH) gene rearrangement from normal B cells purified from lymph nodes. The critical points of our method are pre-stimulation of B cells with IL-21 and CD40-ligand (CD40L), followed by consecutive transfection of highly concentrated Yamanaka factors using a retroviral vector...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28482067/frequent-akt1e17k-mutations-in-skull-base-meningiomas-are-associated-with-mtor-and-erk1-2-activation-and-reduced-time-to-tumor-recurrence
#9
Ümmügülsüm Yesilöz, Elmar Kirches, Christian Hartmann, Johannes Scholz, Siegfried Kropf, Felix Sahm, Makoto Nakamura, Christian Mawrin
Background.: Skull base meningiomas are considered to be difficult for surgical treatment. We wondered whether genetic alterations recently identified in benign non-NF2-mutated World Health Organization (WHO) grade I meningiomas are related to clinical features of skull base meningiomas and whether druggable signaling pathways are activated. Methods.: We analyzed 93 skull base meningiomas (82 WHO grade I, 11 WHO grade II) for mutations of hot spots or the most relevant exons of AKT1, KLF4/TRAF7, SMO, PI3K, and the TERT promoter...
May 6, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28479419/novel-tumor-suppressor-function-of-klf4-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#10
REVIEW
Ye Shen, Taylor J Chen, H Daniel Lacorazza
Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in pediatric patients. Despite advances in the treatment of this disease, many children with T-cell ALL (T-ALL) die from disease relapse due to low responses to standard chemotherapy and the lack of a targeted therapy that selectively eradicates the chemoresistant leukemia-initiating cells (LICs) responsible for disease recurrence. We recently reported that the reprogramming factor KLF4 has tumor-suppressive function in children with T-ALL...
May 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28477135/lentiviral-reprogramming-of-a-t-patient-fibroblasts-to-induced-pluripotent-stem-cells
#11
Sam Nayler, Sergei V Kozlov, Martin F Lavin, Ernst Wolvetang
Reprogramming of cells enables generation of pluripotent stem cells and resulting progeny through directed differentiation, making this technology an invaluable tool for the study of human development and disease. Reprogramming occurs with a wide range of efficiency, a culmination of intrinsic and extrinsic factors including the tissue of origin, the passage number and culture history of the target cells. Another major factor affecting reprogramming is the methodology used and the quality of the reprogramming process itself, including for conventional viral-based approaches viral titer and subsequent viral transduction efficiency, including downstream transgene insertion and stoichiometry...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28473707/dna-methylation-and-transcriptome-changes-associated-with-cisplatin-resistance-in-ovarian-cancer
#12
Riikka J Lund, Kaisa Huhtinen, Jussi Salmi, Juha Rantala, Elizabeth V Nguyen, Robert Moulder, David R Goodlett, Riitta Lahesmaa, Olli Carpén
High-grade serous ovarian cancer is the most common ovarian cancer type. Although the combination of surgery and platinum-taxane chemotherapy provide an effective treatment, drug resistance frequently occurs leading to poor outcome. In order to clarify the molecular mechanisms of drug resistance, the DNA methylation and transcriptomic changes, associated with the development of drug resistance in high-grade serous ovarian cancer, were examined from patient derived malignant ascites cells. In parallel with large-scale transcriptome changes, cisplatin resistance was associated with loss of hypermethylation at several CpG sites primarily localized in the intergenic regions of the genome...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28467928/hybrid-cellular-metabolism-coordinated-by-zic3-and-esrrb-synergistically-enhances-induction-of-naive-pluripotency
#13
Masamitsu Sone, Nobuhiro Morone, Tomonori Nakamura, Akito Tanaka, Keisuke Okita, Knut Woltjen, Masato Nakagawa, John E Heuser, Yasuhiro Yamada, Shinya Yamanaka, Takuya Yamamoto
Naive pluripotent stem cells (PSCs) utilize both glycolysis and oxidative phosphorylation (OXPHOS) to satisfy their metabolic demands. However, it is unclear how somatic cells acquire this hybrid energy metabolism during reprogramming toward naive pluripotency. Here, we show that when transduced with Oct4, Sox2, and Klf4 (OSK) into murine fibroblasts, Zic3 and Esrrb synergistically enhance the reprogramming efficiency by regulating cellular metabolic pathways. These two transcription factors (TFs) cooperatively activate glycolytic metabolism independently of hypoxia inducible factors (HIFs)...
May 2, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28465093/generation-genome-edition-and-characterization-of-ipsc-lines-from-a-patient-with-coenzyme-q10-deficiency-harboring-a-heterozygous-mutation-in-coq4-gene
#14
Damià Romero-Moya, Julio Castaño, Carlos Santos-Ocaña, Plácido Navas, Pablo Menendez
We report the generation, CRISPR/Cas9-edition and characterization of induced pluripotent stem cell (iPSC) lines from a patient with coenzyme Q10 deficiency harboring the heterozygous mutation c.483G>C in the COQ4 gene. iPSCs were generated using non-integrative Sendai Viruses containing the reprogramming factors OCT4, SOX2, KLF4 and C-MYC. The iPSC lines carried the c.483G>C COQ4 mutation, silenced the OKSM expression and were mycoplasma-free. They were bona fide pluripotent cells as characterized by morphology, immunophenotype/gene expression for pluripotent-associated markers/genes, NANOG and OCT4 promoter demethylation, karyotype and teratoma formation...
September 16, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/28460880/transdifferentiation-and-reprogramming-overview-of-the-processes-their-similarities-and-differences
#15
REVIEW
Artur Cieślar-Pobuda, Viktoria Knoflach, Mikael V Ringh, Joachim Stark, Wirginia Likus, Krzysztof Siemianowicz, Saeid Ghavami, Andrzej Hudecki, Jason L Green, Marek J Łos
Reprogramming, or generation of induced pluripotent stem (iPS) cells (functionally similar to embryonic stem cells or ES cells) by the use of transcription factors (typically: Oct3/4, Sox2, c-Myc, Klf4) called "Yamanaka factors" (OSKM), has revolutionized regenerative medicine. However, factors used to induce stemness are also overexpressed in cancer. Both, ES cells and iPS cells cause teratoma formation when injected to tissues. This raises a safety concern for therapies based on iPS derivates. Transdifferentiation (lineage reprogramming, or -conversion), is a process in which one mature, specialized cell type changes into another without entering a pluripotent state...
April 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28460480/htert-promotes-gastric-intestinal-metaplasia-by-upregulating-cdx2-via-nf-%C3%AE%C2%BAb-signaling-pathway
#16
Bai-Jun Chen, Shuo Zeng, Rui Xie, Chang-Jiang Hu, Su-Ming Wang, Yu-Yun Wu, Yu-Feng Xiao, Shi-Ming Yang
BACKGROUND: hTERT has been reported involved in the proliferation and metastasis of gastric cancer, but the role of hTERT in gastric intestinal metaplasia, a premalignant lesion of the gastric mucosa was unknown. The aim of the present study was to investigate the role of hTERT in GIM and the effect of hTERT on CDX2 expression in gastric cells. RESULTS: Experiments showed that expression of hTERT was significantly higher in GIM than in normal gastric mucosa. Moreover, hTERT increased the KLF4 level via NF-κB during GIM...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28460458/inactivation-of-p38-mapk-contributes-to-stem-cell-like-properties-of-non-small-cell-lung-cancer
#17
Yan Fang, Juan Wang, Guanwen Wang, Chen Zhou, Peng Wang, Shuangtao Zhao, Shaorong Zhao, Shan Huang, Weijun Su, Pengling Jiang, Antao Chang, Rong Xiang, Peiqing Sun
Cancer stem cells (CSCs) are recognized as the major source for cancer initiation and recurrence. Yet, the mechanism by which the cancer stem cell properties are acquired and maintained in a cancer cell population is not well understood. In the current study, we observed that the level of active p38 MAPK is downregulated, while the level of the stemness marker SOX2 is upregulated in lung cancer tissues as compared to normal tissues. We further demonstrated that inactivation of p38 is a potential mechanism contributing to acquisition and maintenance of cancer stem cell properties in non-small cell lung cancer (NSCLC) cells...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28456659/n-myc-downstream-regulated-gene-1-ndrg1-promotes-the-stem-like-properties-of-lung-cancer-cells-through-stabilized-c-myc
#18
Yongfang Wang, You Zhou, Feng Tao, Shoujie Chai, Xia Xu, Ying Yang, Yiming Yang, Haiyan Xu, Kai Wang
Tumor-initiating cells (TICs) play an important role in tumorigenesis and development for many various tissue origin cancers including non-small cell lung cancer (NSCLC). However, the mechanism to maintain TICs in NSCLC is still largely unknown. Here, we evaluated differences of mRNA expression between parental and oncosphere cells that enriched TICs. We found that N-myc downstream regulated gene 1(NDRG1) was upregulated in oncosphere cells derived from human NSCLC cell lines and primary NSCLC cells. NDRG1 promoted stem-like properties of LTICs in NSCLC including iPSC (induced pluripotent stem cell) factors (OCT4, SOX2, KLF4, and C-MYC), the spheres-forming ability and the tumorigenicity of NSCLC...
April 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28455313/transient-transcription-factor-oskm-expression-is-key-towards-clinical-translation-of-in%C3%A2-vivo-cell-reprogramming
#19
Irene de Lázaro, Giulio Cossu, Kostas Kostarelos
Reprogramming adult, fully differentiated cells to pluripotency in vivo via Oct3/4, Sox2, Klf4 and c-Myc (OSKM) overexpression has proved feasible in various independent studies and could be used to induce tissue regeneration owing to the proliferative capacity and differentiation potential of the reprogrammed cells. However, a number of these reports have described the generation of teratomas caused by sustained reprogramming, which precludes the therapeutic translation of this technology. A recent study by the Izpisúa-Belmonte laboratory described a cyclic regime for short-term OSKM expression in vivo that prevents complete reprogramming to the pluripotent state as well as tumorigenesis...
April 28, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28455240/hepatitis-b-virus-pres1-facilitates-hepatocellular-carcinoma-development-by-promoting-appearance-and-self-renewal-of-liver-cancer-stem-cells
#20
Zhixin Liu, Xuechen Dai, Tianci Wang, Chengcheng Zhang, Wenjun Zhang, Wei Zhang, Qi Zhang, Kailang Wu, Fang Liu, Yingle Liu, Jianguo Wu
Hepatitis B virus (HBV) is a major etiologic agent of hepatocellular carcinoma (HCC). However, the molecular mechanism by which HBV infection contributes to HCC development is not fully understood. Here, we initially showed that HBV stimulates the production of cancer stem cells (CSCs)-related markers (CD133, CD117 and CD90) and CSCs-related genes (Klf4, Sox2, Nanog, c-Myc and Oct4) and facilitates the self-renewal of CSCs in human hepatoma cells. Cellular and clinical studies revealed that HBV facilitates hepatoma cell growth and migration, enhances white blood cell (WBC) production in the sera of patients, stimulates CD133 and CD117 expression in HCC tissues, and promotes the CSCs generation of human hepatoma cells and clinical cancer tissues...
April 25, 2017: Cancer Letters
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