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https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#1
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28632762/dot1l-inhibitor-improves-early-development-of-porcine-somatic-cell-nuclear-transfer-embryos
#2
Jia Tao, Yu Zhang, Xiaoyuan Zuo, Renyun Hong, Hui Li, Xing Liu, Weiping Huang, Zubing Cao, Yunhai Zhang
Incomplete epigenetic reprogramming of the genome of donor cells causes poor early and full-term developmental efficiency of somatic cell nuclear transfer (SCNT) embryos. Previous research indicate that inhibition of the histone H3 K79 methyltransferase DOT1L, using a selective pharmacological inhibitor EPZ004777 (EPZ), significantly improved reprogramming efficiency during the generation of mouse induced pluripotent stem cells. However, the roles of DOT1L in porcine nuclear transfer-mediated cellular reprogramming are not yet known...
2017: PloS One
https://www.readbyqxmd.com/read/28618452/murine-melanoma-cells-incomplete-reprogramming-using-non-viral-vector
#3
D A D Câmara, A S Porcacchia, A S Costa, R A Azevedo, I Kerkis
OBJECTIVES: The reprogramming of cancer cells into induced pluripotent stem cells or less aggressive cancer cells can provide a modern platform to study cancer-related genes and their interactions with cell environment before and after reprogramming. Herein, we aimed to investigate the reprogramming capacity of murine melanoma B16F10 cells. MATERIALS AND METHODS: The B16F10 was transfected using non-viral circular DNA plasmid containing the genes Sox-2, Oct4, Nanog, Lin28 and green fluorescent protein (GFP)...
June 15, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28614211/mixed-gonadal-germ-cell-tumor-composed-of-a-spermatocytic-tumor-like-component-and-germinoma-arising-in-gonadoblastoma-in-a-phenotypic-woman-with-a-46-xx-peripheral-karyotype-report-of-the-first-case
#4
Alejandro A Gru, Eli S Williams, Dengfeng Cao
We report a unique case of gonadal mixed germ cell tumor (GCT) composed of a predominantly spermatocytic tumor (ST)-like component and a minor component of germinoma arising in gonadoblastoma in a phenotypic woman with a 46, XX peripheral karotype. The patient was a 24-year-old woman (gravida 2, para 1) found to have a 7 cm pelvic mass during routine obstetric ultrasound examination at 20 weeks gestational age. She underwent a left salpingo-gonadectomy at gestational age 23 and 2/7 weeks. She recovered well and delivered a healthy baby at full term...
June 13, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28596507/let-7g-suppresses-both-canonical-and-non-canonical-nf-%C3%AE%C2%BAb-pathways-in-macrophages-leading-to-anti-atherosclerosis
#5
Yung-Song Wang, Edward Hsi, Hsin-Yun Cheng, Shih-Hsien Hsu, Yi-Chu Liao, Suh-Hang H Juo
Transformation of macrophages to foam cells contributes to atherosclerosis. Here, we report that let-7g reduces macrophage transformation and alleviates foam cell apoptosis by suppressing both canonical and non-canonical NF-κB pathways. In the canonical pathway, let-7g inhibits phosphorylation of IKKβ and IκB, down-regulates SREBF2 and miR-33a, and up-regulates ABCA1. In the non-canonical pathway, let-7g directly knocks down MEKK1, IKKα and ablates IKKα phosphorylation. Let-7g's effects in macrophages can be almost completely blocked by inactivation of NF-κB signaling, which suggests that let-7g's effects are primarily mediated through the suppression of NF-κB pathways...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28583172/fluorescent-tagged-episomals-for-stoichiometric-induced-pluripotent-stem-cell-reprogramming
#6
Christopher E Schmitt, Blanca M Morales, Ellen M H Schmitz, John S Hawkins, Carlos O Lizama, Joan P Zape, Edward C Hsiao, Ann C Zovein
BACKGROUND: Non-integrating episomal vectors have become an important tool for induced pluripotent stem cell reprogramming. The episomal vectors carrying the "Yamanaka reprogramming factors" (Oct4, Klf, Sox2, and L-Myc + Lin28) are critical tools for non-integrating reprogramming of cells to a pluripotent state. However, the reprogramming process remains highly stochastic, and is hampered by an inability to easily identify clones that carry the episomal vectors. METHODS: We modified the original set of vectors to express spectrally separable fluorescent proteins to allow for enrichment of transfected cells...
June 5, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28582547/the-torc1-2-inhibitor-tak228-sensitizes-atypical-teratoid-rhabdoid-tumors-to-cisplatin-induced-cytotoxicity
#7
Jeffrey A Rubens, Sabrina Z Wang, Antoinette Price, Melanie F Weingart, Sariah J Allen, Brent A Orr, Charles G Eberhart, Eric H Raabe
Background: Atypical teratoid/rhabdoid tumors (AT/RTs) are deadly pediatric brain tumors driven by LIN28. Mammalian target of rapamycin (mTOR) is activated in many deadly, drug-resistant cancers and governs important cellular functions such as metabolism and survival. LIN28 regulates mTOR in normal cells. We therefore hypothesized that mTOR is activated downstream of LIN28 in AT/RT, and the brain-penetrating mTOR complex 1 and 2 (mTORC1/2) kinase inhibitor TAK228 would reduce AT/RT tumorigenicity...
June 3, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28577895/sox2-regulates-m%C3%A3-ller-glia-reprogramming-and-proliferation-in-the-regenerating-zebrafish-retina-via-lin28-and-ascl1a
#8
Ryne A Gorsuch, Manuela Lahne, Clare E Yarka, Michael E Petravick, Jingling Li, David R Hyde
Sox2 is a well-established neuronal stem cell-associated transcription factor that regulates neural development and adult neurogenesis in vertebrates, and is one of the critical genes used to reprogram differentiated cells into induced pluripotent stem cells. We examined if Sox2 was involved in the early reprogramming-like events that Müller glia undergo as they upregulate many pluripotency- and neural stem cell-associated genes required for proliferation in light-damaged adult zebrafish retinas. In the undamaged adult zebrafish retina, Sox2 is expressed in Müller glia and a subset of amacrine cells, similar to other vertebrates...
May 31, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28557624/rna-guided-activation-of-pluripotency-genes-in-human-fibroblasts
#9
Kai Xiong, Yan Zhou, Kristian Aabo Blichfeld, Poul Hyttel, Lars Bolund, Kristine Karla Freude, Yonglun Luo
Specific activation of endogenous genes can be achieved by programmable artificial transcription factors (ATFs). In this study, we compared two artificial, programmable, clustered regularly interspaced short palindromic repeats (CRISPR)-based, ubiquitous transcription factors: deficient CRISPR-associated protein 9 (dCas9)-VP64 (CRISPRa) alone, or a combination of dCas9-VP64 and MS2-P65-HSF1 [synergistic activation mediator (SAM) system] mediated activation of five pluripotency genes: KLF4 (K), LIN28 (L), MYC (M), OCT4 (O), and SOX2 (S) in human cells (HEK293T, HeLa, HepG2, and primary fibroblasts)...
June 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28545044/differentiation-of-spontaneously-contracting-cardiomyocytes-from-non-virally-reprogrammed-human-amniotic-fluid-stem-cells
#10
Aaron J Velasquez-Mao, Christopher J M Tsao, Madeline N Monroe, Xavier Legras, Beatrice Bissig-Choisat, Karl-Dimiter Bissig, Rodrigo Ruano, Jeffrey G Jacot
Congenital heart defects are the most common birth defect. The limiting factor in tissue engineering repair strategies is an autologous source of functional cardiomyocytes. Amniotic fluid contains an ideal cell source for prenatal harvest and use in correction of congenital heart defects. This study aims to investigate the potential of amniotic fluid-derived stem cells (AFSC) to undergo non-viral reprogramming into induced pluripotent stem cells (iPSC) followed by growth-factor-free differentiation into functional cardiomyocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28536261/the-let-7-lin28-axis-regulates-activation-of-hepatic-stellate-cells-in-alcoholic-liver-injury
#11
Kelly McDaniel, Li Huang, Keisaku Sato, Nan Wu, Tami Annable, Tianhao Zhou, Sugeily Ramos-Lorenzo, Ying Wan, Qiaobing Huang, Heather Francis, Shannon Glaser, Hidekazu Tsukamoto, Gianfranco Alpini, Fanyin Meng
The let-7/lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs (miRNAs) in different human disorders and cancer development. This study evaluated the role of the let-7/lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly downregulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (hHSCs) with lipopolysaccharide (LPS) and TGF-β significantly decreased the expressions of let-7a and let-7b...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28505005/gastric-cancer-with-primitive-enterocyte-phenotype-an-aggressive-subgroup-of-intestinal-type-adenocarcinoma
#12
Sho Yamazawa, Tetsuo Ushiku, Aya Shinozaki-Ushiku, Akimasa Hayashi, Akiko Iwasaki, Hiroyuki Abe, Amane Tagashira, Hiroharu Yamashita, Yasuyuki Seto, Hiroyuki Aburatani, Masashi Fukayama
A primitive cell-like gene expression signature is associated with aggressive phenotypes of various cancers. We assessed the expression of phenotypic markers characterizing primitive cells and its correlation with clinicopathologic and molecular characteristics in gastric cancer. Immunohistochemical analysis of a panel of primitive phenotypic markers, including embryonic stem cell markers (OCT4, NANOG, SALL4, CLDN6, and LIN28) and known oncofetal proteins (AFP and GPC3), was performed using tissue microarray on 386 gastric cancers...
May 12, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28500786/dovitinib-enhances-temozolomide-efficacy-in-glioblastoma-cells
#13
Thatchawan Thanasupawat, Suchitra Natarajan, Amy Rommel, Aleksandra Glogowska, Hugo Bergen, Jerry Krcek, Marshall Pitz, Jason Beiko, Sherry Krawitz, Inder M Verma, Saeid Ghavami, Thomas Klonisch, Sabine Hombach-Klonisch
The multikinase inhibitor and FDA-approved drug dovitinib (Dov) crosses the blood-brain barrier and was recently used as single drug application in clinical trials for GB patients with recurrent disease. The Dov-mediated molecular mechanisms in GB cells are unknown. We used GB patient cells and cell lines to show that Dov downregulated the stem cell protein Lin28 and its target high-mobility group protein A2 (HMGA2). The Dov-induced reduction in pSTAT3(Tyr705) phosphorylation demonstrated that Dov negatively affects the STAT3/LIN28/Let-7/HMGA2 regulatory axis in GB cells...
May 13, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28494471/inhibition-of-neurotensin-receptor-1-induces-intrinsic-apoptosis-via-let-7a-3p-bcl-w-axis-in-glioblastoma
#14
Zhen Dong, Qian Lei, Rui Yang, Shunqin Zhu, Xiao-Xue Ke, Liqun Yang, Hongjuan Cui, Liang Yi
Backgroud:Glioblastoma is a kind of highly malignant and aggressive tumours in the central nervous system. Previously, we found that neurotensin (NTS) and its high-affinity receptor 1 (NTSR1) had essential roles in cell proliferation and invasiveness of glioblastoma. Unexpectedly, cell death also appeared by inhibition of NTSR1 except for cell cycle arrest. However, the mechanisms were remained to be further explored. METHODS: Cells treated with SR48692, a selective antagonist of NTSR1, or NTSR1 shRNA were stained with Annexin V-FITC/PI and the apoptosis was assessed by flow cytometry...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28482074/carbon-ion-irradiation-abrogates-lin28b-induced-x-ray-resistance-in-melanoma-cells
#15
Seong-Joon Park, Kyu Heo, Chulwon Choi, Kwangmo Yang, Akiko Adachi, Hiroko Okada, Yukari Yoshida, Tatsuya Ohno, Takashi Nakano, Akihisa Takahashi
The Lin28/let-7 axis plays an important role in tumor initiation and developmental processes. Lin28B is upregulated in a variety of cancers, and its overexpression enhances cancer cell proliferation and radioresistance through the suppression of let-7 micro RNA expression. In this study, we investigated the role of the Lin28/let7 axis as a target for radiosensitization of melanoma cancer cells. The overexpression of Lin28B reduced mature let-7 microRNA expression in melanoma cell lines, and enhanced the sphere-forming ability of melanoma cell lines, which is a characteristic of cancer stem cell (CSC) populations...
May 8, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28434825/rna-binding-proteins-in-human-oogenesis-balancing-differentiation-and-self-renewal-in-the-female-fetal-germline
#16
Roseanne Rosario, Andrew J Childs, Richard A Anderson
Primordial germ cells undergo three significant processes on their path to becoming primary oocytes: the initiation of meiosis, the formation and breakdown of germ cell nests, and the assembly of single oocytes into primordial follicles. However at the onset of meiosis, the germ cell becomes transcriptionally silenced. Consequently translational control of pre-stored mRNAs plays a central role in coordinating gene expression throughout the remainder of oogenesis; RNA binding proteins are key to this regulation...
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28423547/genomic-imbalances-are-involved-in-mir-30c-and-let-7a-deregulation-in-ovarian-tumors-implications-for-hmga2-expression
#17
Antonio Agostini, Marta Brunetti, Ben Davidson, Claes G Tropé, Sverre Heim, Ioannis Panagopoulos, Francesca Micci
The High-mobility group AT-hook 2 protein (HMGA2) is involved in different processes during tumorigenesis. High expression levels of HMGA2 are found in various types of cancer, with recent studies highlighting the important role of miRNAs in the regulation of HMGA2 expression. We report a study of 155 ovarian tumors (30 sex-cord stromal tumors, 22 borderline tumors, and 103 carcinomas) analyzed for HMGA2 expression as well as the expression of two miRNAs targeting this gene, let-7a and miR-30c. We also evaluated the expression of the fragile histidine triad (FHIT) and lin28 homologues (LIN28A/B) genes which are known to be an enhancer of miR-30c expression and a repressor of let-7a, respectively...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400788/the-lin28-let-7-pathway-in-cancer
#18
REVIEW
Julien Balzeau, Miriam R Menezes, Siyu Cao, John P Hagan
Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28395807/generation-and-characterization-of-human-ipsc-line-from-cd34-cells-isolated-from-umbilical-cord-blood-belonging-to-indian-origin
#19
Sophia Fernandes, Manasi Talwadekar, Raju Agarwal, Velu Nair, Vaijayanti Kale, Lalita Limaye
We describe here the reprogramming of CD34(+) cells isolated from umbilical cord blood obtained after full term delivery of a healthy female child of Indian origin. The cells were nucleofected by episomal vectors expressing Oct4, Sox2, L-Myc, Klf4, Lin28 and p53DD (negative mutation in p53). Colonies were identified by alkaline phosphatase staining and characterized for expression of pluripotency markers at protein level by immunofluorescence, flow cytometry and at transcript level by PCR. Genomic stability of the cell line was checked by G-banded karyotype...
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28395748/generation-of-induced-pluripotent-stem-cells-from-peripheral-blood-cd34-hematopoietic-progenitors-of-a-31year-old-healthy-woman
#20
Amornrat Tangprasittipap, Bunyada Jittorntrum, Wasinee Wongkummool, Narisorn Kitiyanant, Alisa Tubsuwan
The MUi019-A human induced pluripotent stem cell line was generated from peripheral blood CD34+ hematopoietic progenitors of a healthy woman using a non-integrative reprogramming method. Episomal vectors carrying reprogramming factors OCT4, SOX2, KLF4, L-MYC, LIN28, and shRNA of TP53 and EBNA-1 were delivered using electroporation. The iPSC line can be used as a control in studying disease mechanisms. Furthermore, gene editing approaches can be used to introduce specific mutations into the MUi019-A to model disease while the cell type affected by the disease is inaccessible...
April 2017: Stem Cell Research
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