Reprogramming of Mouse and Human Cells to Pluripotency Using Mature MicroRNAs

Miyoshi, Norikatsu; Ishii, Hideshi; Nagano, Hiroaki; Haraguchi, Naotsugu; Dewi, Dyah Laksmi; Kano, Yoshihiro; Nishikawa, Shinpei; Tanemura, Masahiro; Mimori, Koshi; Tanaka, Fumiaki; Saito, Toshiyuki; Nishimura, Junichi; Takemasa, Ichiro; Mizushima, Tsunekazu; Ikeda, Masataka; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Doki, Yuichiro; Mori, Masaki

doi:10.1016/j.stem.2011.05.001

Cited by 688 publications

(531 citation statements)

References 30 publications

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“…1a). In brief, RNA-iPSCs are reprogrammed from human skin fibroblasts by a single transfection of an miR cocktail (miR-200c, miR-302a-d and miR-369) 31 and subsequent daily transfections of mature mRNA transcripts encoding Klf4, Oct4, Sox2, c-Myc and Lin28 for 10-12 d, until the formation of mature iPSC colonies 32 (Fig. 1b).…”

Section: Resultsmentioning

confidence: 99%

miR-128 represses L1 retrotransposition by binding directly to L1 RNA

Hamdorf

Idica

Zisoulis

et al. 2015

Nat Struct Mol Biol

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VOLUME 22 NUMBER 10 OCTOBER 2015 nature structural & molecular biology a r t i c l e s microRNAs (miRs) are a class of small (~22-nt) genomically encoded molecules that inhibit translational initiation and stimulate decay of mRNA targets 1,2 . miRs are transcribed by RNA polymerase II and processed by the RNase III enzymes-Dicer and Drosha with its binding partner, DGCR8-to produce short double-stranded RNAs in the nucleus. One strand associates with the Argonaute (Ago) protein, thus forming the miR-mediated silencing complex (miRISC). miRs guide the pairing of miRISC, with imperfect complementarity, to sequences in target mRNAs, thus resulting in their subsequent destabilization and translational repression of the target 3 . The 'seed sequence' , at nucleotides 2-8, is a key determinant for miRISC-target recognition 4,5 . Recent data have shown that 35-40% of miR-binding sites are found in 3′ untranslated regions (UTRs), 40-50% in coding regions and <5% in 5′-UTR regions of mRNAs 6,7 . More than 60% of the human transcriptome has been predicted to be under miR regulation, thus making this post-transcriptional control pathway as important as protein pathways in the regulation of cell functions 2 . It is clear that miRs have essential roles in regulating diverse functions in normal and diseased cells 8,9 .L1 belongs to the most abundant class of autonomous transposable elements 10 . Human L1 contains two open reading frames, ORF1 and ORF2, which encode a protein with RNA-binding and nucleotide acid-chaperone activity (ORF1) 11 and a protein with endonuclease and reverse-transcriptase activities (ORF2) 12-15 , respectively. L1 mobilizes replicatively from one location in the genome to another by a 'copy-and-paste' mechanism, and it has been proposed to be a remnant of an ancient retrovirus 12,16 . Active and inactive L1s have been implicated in the evolution of mammalian genomes and are linked to cell-based diseases, including cancer [17][18][19] . In addition, somatic L1 insertions are biased toward regions of cancer-specific DNA hypomethylation, thus suggesting that L1 insertions may provide a selective advantage during tumorigenesis 20 . Mechanisms that operate at different levels in gene-expression hierarchies have been selected to control transposition-mediated mutagenesis and mitigate the potential negative effects of newly inserted elements. In germ cells, a specific small-RNA subtype (piwi-interacting RNAs (piRNAs)) efficiently counteracts L1 activity, but these RNAs are not expressed in nongerm cells 21,22 . Somatic cells attenuate element mobilization by DNA methylation of the L1 promoter 23 . Other methods of regulation are mediated by APOBEC proteins 24,25 , microprocessor interactions 26 and Ago-mediated RNA interference in mouse embryonic stem cells 27 . L1-promoter silencing is greatly attenuated, and L1 transcription is reactivated in hypomethylated cells, such as cancer cells and tumor-initiating cells, and is also reactivated during reprogramming [28][29][30] . Because miRs act as regulators of g...

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Section: Resultsmentioning

confidence: 99%

miR-128 represses L1 retrotransposition by binding directly to L1 RNA

Hamdorf

Idica

Zisoulis

et al. 2015

Nat Struct Mol Biol

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“…In 2008, Lin and colleagues reported the transformation of human skin cancer cells into an ES-like state by overexpression of the miR302 cluster . Very recently, two independent groups announced highly efficient generation of mouse and human iPSCs either by lentiviral delivery of miR302 into fibroblast cells or by transfection of mature miR200c, miR302, and mir369 (Anokye-Danso et al, 2011;Miyoshi et al, 2011). These microRNA iPSCs were indistinguishable from OSKM-iPSCs in pluripotency marker expression, teratoma formation, and germline transmission (in mice).…”

Section: Generating Ips Cells By Micrornasmentioning

confidence: 99%

Mechanism and methods to induce pluripotency

Wang

2011

Protein Cell

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Pluripotent stem cells are able to self-renew indefinitely and differentiate into all types of cells in the body. They can thus be an inexhaustible source for future cell transplantation therapy to treat degenerative diseases which currently have no cure. However, non-autologous cells will cause immune rejection. Induced pluripotent stem cell (iPSC) technology can convert somatic cells to the pluripotent state, and therefore offers a solution to this problem. Since the first generation of iPSCs, there has been an explosion of relevant research, from which we have learned much about the genetic networks and epigenetic landscape of pluripotency, as well as how to manipulate genes, epigenetics, and microRNAs to obtain iPSCs. In this review, we focus on the mechanism of cellular reprogramming and current methods to induce pluripotency. We also highlight new problems emerging from iPSCs. Better understanding of the fundamental mechanisms underlying pluripotenty and refining the methodology of iPSC generation will have a significant impact on future development of regenerative medicine.

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“…56 Two independent groups have now demonstrated that lentiviral expression of miR-302/ miR-367 cluster and a cocktail of miRNAs (miR-200c, miR302a-d, miR-369-3p, and miR-369-5p) may reprogram human fibroblasts to iPSCs efficiently. 57 The cells that reexpressed human ESC factors featuring global gene expression analogous to human ESCs were named miRNA-iPSCs. This constitutes the first proof of principle to demonstrate that iPSCs may be obtained with miRNAs without the need for genomic integration of foreign DNA.…”

Section: Mirnas In Cellular Reprogrammingmentioning

confidence: 99%