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https://www.readbyqxmd.com/read/27895551/oct4-methylation-mediated-silencing-as-an-epigenetic-barrier-preventing-m%C3%A3-ller-glia-dedifferentiation-in-a-murine-model-of-retinal-injury
#1
Luis I Reyes-Aguirre, Monica Lamas
Müller glia (MG) is the most abundant glial type in the vertebrate retina. Among its many functions, it is capable of responding to injury by dedifferentiating, proliferating, and differentiating into every cell types lost to damage. This regenerative ability is notoriously absent in mammals. We have previously reported that cultured mammalian MG undergoes a partial dedifferentiation, but fails to fully acquire a progenitor phenotype and differentiate into neurons. This might be explained by a mnemonic mechanism comprised by epigenetic traits, such as DNA methylation...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27879219/induced-pluripotent-stem-cells-ipscs-derived-from-cerebrotendinous-xanthomatosis-ctx-patient-s-fibroblasts-carrying-a-r395s-mutation
#2
Philip Höflinger, Stefan Hauser, Yvonne Theurer, Stefanie Weißenberger, Carlo Wilke, Ludger Schöls
Induced pluripotent stem cells (iPSCs) were generated from dermal fibroblasts from a 60-year-old cerebrotendinous xanthomatosis (CTX) patient, carrying a homozygous mutation c. [1183C>A]; p. R395S in CYP27A1. Episomal plasmids encoding the pluripotency genes OCT4, SOX2, KLF4, L-MYC and LIN28 were introduced via electroporation. The generated line iPS-CTX-R395S has no sign of plasmid integration or chromosomal aberration and retained the mutation site in CYP27A1. Furthermore, iPSCs express pluripotency markers and are able to differentiate in all germ layers in vitro...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27879208/generation-of-induced-pluripotent-stem-cells-ipscs-from-a-retinoblastoma-patient-carrying-a-c-2663g-a-mutation-in-rb1-gene
#3
Sicong Zeng, Lvjun Liu, Qi Ouyang, Yan Zhao, Ge Lin, Liang Hu, Wen Li
Skin fibroblasts were obtained from a male patient diagnosed with retinoblastoma (RB) carrying a c.2663G>A mutation in the 25 exon of RB1 gene. RB-iPS cells was generated via delivered four reprogramming factors (OCT4, SOX2, NANOG and LIN28) into these skin fibroblasts. The RB-iPS cells retained the RB1 heterozygous mutation resulted in a truncated RB1 mRNA. Characteristic tests proved that the iPSC line presented typical markers of pluripotency and had the capability to form the three germ layers in vitro...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27822179/plasmid-based-generation-of-induced-neural-stem-cells-from-adult-human-fibroblasts
#4
Philipp Capetian, Luis Azmitia, Martje G Pauly, Victor Krajka, Felix Stengel, Eva-Maria Bernhardi, Mariana Klett, Britta Meier, Philip Seibler, Nancy Stanslowsky, Andreas Moser, Andreas Knopp, Gabriele Gillessen-Kaesbach, Guido Nikkhah, Florian Wegner, Máté Döbrössy, Christine Klein
Direct reprogramming from somatic to neural cell types has become an alternative to induced pluripotent stem cells. Most protocols employ viral expression systems, posing the risk of random genomic integration. Recent developments led to plasmid-based protocols, lowering this risk. However, these protocols either relied on continuous presence of a variety of small molecules or were only able to reprogram murine cells. We therefore established a reprogramming protocol based on vectors containing the Epstein-Barr virus (EBV)-derived oriP/EBNA1 as well as the defined expression factors Oct3/4, Sox2, Klf4, L-myc, Lin28, and a small hairpin directed against p53...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27798668/the-lin28-expression-in-stallion-testes
#5
Geumhui Lee, Heejun Jung, Minjung Yoon
The molecular markers for specific germ cell stages can be utilized for identifying, monitoring, and separating a particular stage of germ cells. The RNA-binding protein Lin28 is expressed in gonocytes of human fetal testes. The Lin28 expression is restricted to a very small population of spermatogonial cells in human, mice, and monkey. The main objective of this study was to investigate the expression pattern of Lin28 in stallion testes at different reproductive stages. Based on the presence or absence of full spermatogenesis and lumina in seminiferous tubules, the testicular samples were categorized into two reproductive stages pre-pubertal and post-pubertal...
2016: PloS One
https://www.readbyqxmd.com/read/27789410/lymphoblast-derived-integration-free-ipsc-lines-from-a-female-and-male-alzheimer-s-disease-patient-expressing-different-copy-numbers-of-a-coding-cnv-in-the-alzheimer-risk-gene-cr1
#6
Friederike Schröter, Kristel Sleegers, Caroline Van Cauwenberghe, Martina Bohndorf, Wasco Wruck, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a female and male patient diagnosed with Alzheimer's disease (AD) with different genotypes of a functional copy number variation (CNV) in the AD risk gene CR1 were used to generate integration-free induced pluripotent stem cells (iPSCs) employing episomal plasmids expressing OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. The iPSCs retained the CR1 CNV, and comparative transcriptome analyses with the human embryonic stem cell line H1 revealed a Pearson correlation of 0.956 for AD1-CR10 and 0...
October 19, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789408/lymphoblast-derived-integration-free-ips-cell-line-from-a-female-67-year-old-alzheimer-s-disease-patient-with-trem2-r47h-missense-mutation
#7
Friederike Schröter, Kristel Sleegers, Elise Cuyvers, Martina Bohndorf, Wasco Wruck, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a female patient diagnosed with Alzheimer's disease (AD) possessing the missense mutation TREM2 p.R47H were used to generate integration-free induced pluripotent stem cells (iPSCs) employing episomal plasmids expressing OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. The iPSCs retained the TREM2 mutation, and were defined as pluripotent based on (i) expression of pluripotent-associated markers, (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptomes of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0...
October 20, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789405/episomal-plasmid-based-generation-of-an-ipsc-line-from-a-79-year-old-individual-carrying-the-apoe4-4-genotype-i11001
#8
Shadaan Zulfiqar, Barbara Fritz, Katja Nieweg
In this study, lymphoblastoid cells derived from a 79-year old individual with a history of progressive presenile dementia, were used to generate iPS cells, employing episomal plasmids expressing OCT4, SOX2, KLF4, LIN28, L-MYC and a p53 shRNA. The individual was homozygous for the APOE4 allele. The resulting iPS cells had a normal karyotype, retained the APOE4/4 genotype, expressed pluripotency markers, were free of genomically integrated plasmids, and could be differentiated into cell type representatives from the three germ layers in vitro...
September 23, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789402/episomal-plasmid-based-generation-of-an-ipsc-line-from-an-83-year-old-individual-carrying-the-apoe4-4-genotype-i10984
#9
Shadaan Zulfiqar, Barbara Fritz, Katja Nieweg
In this study, lymphoblastoid cells derived from a 83-year old individual with a 15year history of progressive presenile dementia, were used to generate iPS cells, employing episomal plasmids expressing OCT4, SOX2, LIN28, L-MYC and a p53 shRNA. The individual was homozygous for the APOE4 allele. The resulting iPS cells had a normal karyotype, retained the APOE4/4 genotype, expressed pluripotency markers, were free of genomically integrated plasmids, and could be differentiated into cell type representatives from the three germ layers in vitro...
September 24, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789396/derivation-of-induced-pluripotent-stem-cells-from-a-familial-alzheimer-s-disease-patient-carrying-the-l282f-mutation-in-presenilin-1
#10
Anna Poon, Tong Li, Carlota Pires, Troels T Nielsen, Jørgen E Nielsen, Bjørn Holst, Andras Dinnyes, Poul Hyttel, Kristine K Freude
Mutations in presenilin 1 (PSEN1) lead to the most aggressive form of familial Alzheimer's disease (AD). Human induced pluripotent stem cells (hiPSCs) derived from AD patients can be differentiated and used for disease modeling. Here, we derived hiPSC from skin fibroblasts obtained from an AD patient carrying a L282F mutation in PSEN1. We transfected skin fibroblasts with episomal iPSC reprogramming vectors targeting human OCT4, SOX2, L-MYC, KLF4, NANOG, LIN28, and short hairpin RNA against TP53. Our hiPSC line, L282F-hiPSC, displayed typical stem cell characteristics with consistent expression of pluripotency genes and the ability to differentiation into the three germ layers...
September 28, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27777941/a-review-of-rett-syndrome-rtt-with-induced-pluripotent-stem-cells
#11
Vellingiri Balachandar, Venkatesan Dhivya, Mohan Gomathi, Subramaniam Mohanadevi, Balasubramanian Venkatesh, Bharathi Geetha
Human induced pluripotent stem cells (hiPSCs) are pluripotent stem cells generated from somatic cells by the introduction of a combination of pluripotency-associated genes such as OCT4, SOX2, along with either KLF4 and c-MYC or NANOG and LIN28 via retroviral or lentiviral vectors. Most importantly, hiPSCs are similar to human embryonic stem cells (hESCs) functionally as they are pluripotent and can potentially differentiate into any desired cell type when provided with the appropriate cues, but do not have the ethical issues surrounding hESCs...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27776272/mature-let-7-mirnas-fine-tune-expression-of-lin28b-in-pluripotent-human-embryonic-stem-cells
#12
Nelly Rahkonen, Aki Stubb, Maia Malonzo, Sanna Edelman, Maheswara Reddy Emani, Elisa Närvä, Harri Lähdesmäki, Hannele Ruohola-Baker, Riitta Lahesmaa, Riikka Lund
MicroRNAs (miRNA) are central regulators of diverse biological processes and are important in the regulation of stem cell self-renewal. One of the widely studied miRNA-protein regulators is the Lin28-Let-7 pair. In this study, we demonstrate that contrary to the well-established models of mouse ES cells (mESC) and transformed human cancer cells, the pluripotent state of human ES cells (hESC) involves expression of mature Let-7 family miRNAs with concurrent expression of all LIN28 proteins. We show that mature Let-7 miRNAs are regulated during hESC differentiation and have opposite expression profile with LIN28B...
September 24, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27773931/the-lin28b-let-7-axis-is-a-novel-therapeutic-pathway-in-multiple-myeloma
#13
S Manier, J T Powers, A Sacco, S V Glavey, D Huynh, M R Reagan, K Z Salem, M Moschetta, J Shi, Y Mishima, C Roche-Lestienne, X Leleu, A M Roccaro, G Q Daley, I M Ghobrial
MYC is a major oncogenic driver of multiple myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA-sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM...
November 11, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27731469/identification-of-small-molecule-inhibitors-of-the-lin28-mediated-blockage-of-pre-let-7g-processing
#14
Helen L Lightfoot, Eric A Miska, Shankar Balasubramanian
The protein Lin28 and microRNA let-7 play critical roles in mammalian development and human disease. Lin28 inhibits let-7 biogenesis through direct interaction with let-7 precursors (pre-let-7). Accumulating evidence in vitro and in vivo suggests this interaction plays a dominant role in embryonic stem cell self-renewal and tumorigenesis. Thus the Lin28-let-7 interaction might be an attractive drug target, if not for the well-known difficulties in targeting protein-RNA interactions with drugs. The identification and development of suitable probe molecules to further elucidate therapeutic potential, as well as mechanistic details of this pathway will be valuable...
October 12, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27681429/wnt-regulates-proliferation-and-neurogenic-potential-of-m%C3%A3-ller-glial-cells-via-a-lin28-let-7-mirna-dependent-pathway-in-adult-mammalian-retinas
#15
Kai Yao, Suo Qiu, Lin Tian, William D Snider, John G Flannery, David V Schaffer, Bo Chen
In cold-blooded vertebrates such as zebrafish, Müller glial cells (MGs) readily proliferate to replenish lost retinal neurons. In mammals, however, MGs lack regenerative capability as they do not spontaneously re-enter the cell cycle unless the retina is injured. Here, we show that gene transfer of β-catenin in adult mouse retinas activates Wnt signaling and MG proliferation without retinal injury. Upstream of Wnt, deletion of GSK3β stabilizes β-catenin and activates MG proliferation. Downstream of Wnt, β-catenin binds to the Lin28 promoter and activates transcription...
September 27, 2016: Cell Reports
https://www.readbyqxmd.com/read/27668966/discovery-of-a-small-molecule-inhibitor-of-protein-microrna-interaction-using-binding-assay-with-a-site-specifically-labeled-lin28
#16
Donghyun Lim, Wan Gi Byun, Ja Young Koo, Hankum Park, Seung Bum Park
MicroRNAs (miRNAs) regulate gene expression by targeting protein-coding transcripts that are involved in various cellular processes. Thus, miRNA biogenesis has been recognized as a novel therapeutic target. Especially, the let-7 miRNA family is well-known for its tumor suppressor functions and is downregulated in many cancer cells. Lin28 protein binds to let-7 miRNA precursors to inhibit their maturation. Herein, we developed a FRET-based, high-throughput screening system to identify small-molecule inhibitors of the Lin28-let-7 interaction...
October 7, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27608441/expression-of-six-proteins-causes-reprogramming-of-porcine-fibroblasts-into-induced-pluripotent-stem-cells-with-both-active-x-chromosomes
#17
Tomokazu Fukuda, Tetsuya Tani, Seiki Haraguchi, Kenichiro Donai, Nobuyoshi Nakajima, Hirohide Uenishi, Takahiro Eitsuka, Makoto Miyagawa, Sanghoun Song, Manabu Onuma, Yumi Hoshino, Eimei Sato, Arata Honda
In this study, we created porcine-induced pluripotent stem (iPS) cells with the expression of six reprogramming factors (Oct3/4, Klf4, Sox2, c-Myc, Lin28, and Nanog). The resulting cells showed growth dependent on LIF (leukemia inhibitory factor) and expression of multiple stem cell markers. Furthermore, the iPS cells caused teratoma formation with three layers of differentiation and had both active X chromosomes (XaXa). Our iPS cells satisfied the both of important characteristics of stem cells: teratoma formation and activation of both X chromosomes...
September 8, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27589897/sarcomatoid-adrenocortical-carcinoma-a-comprehensive-pathological-immunohistochemical-and-targeted-next-generation-sequencing-analysis
#18
Thomas G Papathomas, Eleonora Duregon, Esther Korpershoek, David F Restuccia, Ronald van Marion, Rocco Cappellesso, Nathalie Sturm, Giulio Rossi, Antonella Coli, Nicola Zucchini, Hans Stoop, Wolter Oosterhuis, Laura Ventura, Marco Volante, Ambrogio Fassina, Winand N M Dinjens, Mauro Papotti, Ronald R de Krijger
Adrenocortical carcinomas (ACCs) with sarcomatous areas represent an extremely rare type of highly aggressive malignancy of unknown molecular pathogenesis. The current study was planned to gain insight into its molecular genetics using a targeted next-generation sequencing approach and to explore the status of epithelial-mesenchymal transition (EMT)-associated markers (E-/P-/N-Cadherins, MMP-2/-9 and Caveolin-1), downstream transcriptional regulators of EMT-related signaling pathways (ZEB-1/-2, Slug), stem cell factors (Oct3/4, LIN28, SOX2, SO17, NANOG, CD133, nestin) and markers of adrenocortical origin/ tumorigenesis (SF-1, β-catenin, p53) in phenotypically diverse tumor components of six cases...
August 30, 2016: Human Pathology
https://www.readbyqxmd.com/read/27559824/human-lin28-forms-a-high-affinity-1-1-complex-with-the-106-363-cluster-mirna-mir-363
#19
Daniel T Peters, Herman K H Fung, Vladimir M Levdikov, Tobias Irmscher, Fiona C Warrander, Sandra J Greive, Oleg Kovalevskiy, Harry V Isaacs, Mark Coles, Alfred A Antson
Lin28A is a post-transcriptional regulator of gene expression that interacts with and negatively regulates the biogenesis of let-7 family miRNAs. Recent data suggested that Lin28A also binds the putative tumor suppressor miR-363, a member of the 106~363 cluster of miRNAs. Affinity for this miRNA and the stoichiometry of the protein-RNA complex are unknown. Characterization of human Lin28's interaction with RNA has been complicated by difficulties in producing stable RNA-free protein. We have engineered a maltose binding protein fusion with Lin28, which binds let-7 miRNA with a Kd of 54...
September 13, 2016: Biochemistry
https://www.readbyqxmd.com/read/27559294/characterization-of-gene-expression-patterns-among-artificially-developed-cancer-stem-cells-using-spherical-self-organizing-map
#20
Akimasa Seno, Tomonari Kasai, Masashi Ikeda, Arun Vaidyanath, Junko Masuda, Akifumi Mizutani, Hiroshi Murakami, Tetsuya Ishikawa, Masaharu Seno
We performed gene expression microarray analysis coupled with spherical self-organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors (OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC-specific genes (POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7...
2016: Cancer Informatics
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