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Search results for: Thomson Factor Polycistronic

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#24501429   2014/02/05 To Up

ONSL and OSKM cocktails act synergistically in reprogramming human somatic cells into induced pluripotent stem cells.

The advent of human induced pluripotent stem cells (hiPSC) is revolutionizing many research fields including cell-replacement therapy, drug screening, physiopathology of specific diseases and more basic research such as embryonic development or diseases modeling. Despite the large number of reports on reprogramming methods, techniques in use remain globally inefficient. We present here a new optimized approach to improve this efficiency. After having tested different monocistronic vectors with poor results, we adopted a polycistronic cassette encoding Thomson's cocktail OCT4, NANOG, SOX2 and LIN28 (ONSL) separated by 2A peptides. This cassette was tested in various vector backbones, based on lentivirus or retrovirus under a LTR or EF1 alpha promoter. This allowed us to show that ONSL-carrier retrovectors reprogrammed adult fibroblast cells with a much higher efficiency (up to 0.6%) than any other tested. We then compared the reprogramming efficiencies of two different polycistronic genes, ONSL and OCT4, SOX2, KLF4 and cMYC (OSKM) placed in the same retrovector backbone. Interestingly, in this context ONSL gene reprograms more efficiently than OSKM but OSKM reprograms faster suggesting that the two cocktails may reprogram through distinct pathways. By equally mixing RV-LTR-ONSL and RV-LTR-OSKM, we indeed observed a remarkable synergy, yielding a reprogramming efficiency of >2%. We present here a drastic improvement of the reprogramming efficiency, which opens doors to the development of automated and high throughput strategies of hiPSC production. Furthermore, non-integrative reprogramming protocols (i.e. mRNA) may take advantage of this synergy to boost their efficiency.
Laura Jung, Philippe Tropel, Yohann Moal, Marius Teletin, Eric Jeandidier, Régis Gayon, Christian Himmelspach, Fiona Bello, Cécile André, Adeline Tosch, Ahmed Mansouri, Catherine Bruant-Rodier, Pascale Bouillé, Stéphane Viville

2552 related Products with: ONSL and OSKM cocktails act synergistically in reprogramming human somatic cells into induced pluripotent stem cells.

1 mg10 ug5 x 50 ug1.00 flask1 mg50 ug11.00 flask1.00 flask100 ug/vial

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#17135268   2006/11/29 To Up

Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors.

Micro-RNAs (miRNAs) are a class of non-coding RNAs that post-transcriptionally regulate gene expression via the RNA interference pathway. In addition to roles in normal development, miRNAs have recently been implicated in a range of human diseases, including cancer. We recently demonstrated that a polycistronic cluster of miRNAs, miR-17-92, is oncogenic in a mouse model for Burkitt's lymphoma. This is due, in part, to a reduced apoptotic program. In an effort to understand the regulation of miR-17-92, we have studied the promoter structure of this miRNA cluster. The primary transcript initiates from a consensus initiator sequence downstream of a nonconsensus TATA box. The core promoter region contains two functional E2F transcription factor binding sites. Chromatin immunoprecipitation demonstrates that E2F3 is the primary E2F family member that occupies the promoter. These data place miR-17-92 in a regulatory loop between E2F3 and the miR-17 target E2F1. We propose a model whereby miR-17-92 promotes cell proliferation by shifting the E2F transcriptional balance away from the pro-apoptotic E2F1 and toward the proliferative E2F3 transcriptional network.
Keith Woods, J Michael Thomson, Scott M Hammond

2119 related Products with: Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors.

200ug100ug Lyophilized100.00 ul1 Set100.00 ul100 μg100ug Lyophilized508 μg0.1 mg30 micro gram100.00 ug2 Pieces/Box

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#16380711   2005/12/25 To Up

The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.

Understanding the molecular mechanisms that regulate cellular proliferation and differentiation is a central theme of developmental biology. MicroRNAs (miRNAs) are a class of regulatory RNAs of approximately 22 nucleotides that post-transcriptionally regulate gene expression. Increasing evidence points to the potential role of miRNAs in various biological processes. Here we show that miRNA-1 (miR-1) and miRNA-133 (miR-133), which are clustered on the same chromosomal loci, are transcribed together in a tissue-specific manner during development. miR-1 and miR-133 have distinct roles in modulating skeletal muscle proliferation and differentiation in cultured myoblasts in vitro and in Xenopus laevis embryos in vivo. miR-1 promotes myogenesis by targeting histone deacetylase 4 (HDAC4), a transcriptional repressor of muscle gene expression. By contrast, miR-133 enhances myoblast proliferation by repressing serum response factor (SRF). Our results show that two mature miRNAs, derived from the same miRNA polycistron and transcribed together, can carry out distinct biological functions. Together, our studies suggest a molecular mechanism in which miRNAs participate in transcriptional circuits that control skeletal muscle gene expression and embryonic development.
Jian-Fu Chen, Elizabeth M Mandel, J Michael Thomson, Qiulian Wu, Thomas E Callis, Scott M Hammond, Frank L Conlon, Da-Zhi Wang

2590 related Products with: The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.

100ugBacterial streak100ul50 mg25 mg1000 tests100ug100ug100 ul100ul5 x 50 ug100ug

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