Induction of Dedifferentiation, Genomewide Transcriptional Programming, and Epigenetic Reprogramming by Extracts of Carcinoma and Embryonic Stem Cells

Taranger, C. K.; Noer, Agate; Sørensen, Anita L.; Håkelien, Anne Mari; Boquest, Andrew C.; Collas, Philippe

doi:10.1091/mbc.e05-06-0572

Cited by 252 publications

(218 citation statements)

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“…One important finding is the transcriptional upregulation of Nanog (or Nanog-like transcripts) in cotransfected cells. Ectopic expression of Nanog leads to dedifferentiation and blocks further developmental processes (Taranger et al, 2005). Malignant transformation of teratocarcinomas and germline tumors are caused by ectopic expression of Nanog (Almstrup et al, 2004;Hoei-Hansen et al, 2005;Skotheim et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Combined effects of the two reciprocal t(4;11) fusion proteins MLL·AF4 and AF4·MLL confer resistance to apoptosis, cell cycling capacity and growth transformation

et al. 2006

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The reciprocal chromosomal translocation t(4;11) is correlated with infant, childhood, adult and therapyrelated high-risk acute leukemia. Here, we investigated the biological effects of MLL . AF4, AF4 . MLL or the combination of both reciprocal fusion proteins in a conditional in vitro cell culture model system. Several parameters like cell growth, cell cycling capacity, apoptotic behavior and growth transformation were investigated under physiological and stress conditions. Co-transfected cells displayed the highest resistance against apoptotic triggers, cell cycling capacity and lossof-contact inhibition. These analyses were complemented by gene expression profiling experiments and specific gene signatures were established for each of the three cell lines. Interestingly, co-transfected cells strongly upregulate the homeobox gene Nanog. In combination with Oct4, the Nanog homeoprotein is steering maintenance of pluripotency and self-renewal in embryonic stem cells. Transcription of Nanog and other stem cell factors, like Oct4 and Bmi1, was verified in biopsy material of t(4;11) patient cells which express both reciprocal t(4;11) fusion genes. In conclusion, the presence of both reciprocal MLL fusion proteins confers biological properties known from t(4;11) leukemia, suggesting that each of the two fusion proteins contribute specific properties and, in combination, also synergistic effects to the leukemic phenotype.

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Section: Discussionmentioning

confidence: 99%

Combined effects of the two reciprocal t(4;11) fusion proteins MLL·AF4 and AF4·MLL confer resistance to apoptosis, cell cycling capacity and growth transformation

et al. 2006

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“…An alternative to cell fusion is the exposure of somatic cells to embryonic stem (ES) cell extract 14 . Under these conditions, cell division-dependent reprogramming of gene expression is also observed (FIG.…”

Section: Further Informationmentioning

confidence: 99%

“…Somatic cells permeabilized with streptolysin O can be briefly exposed to ES cell extract and then resealed. After culture of such treated cells, changes in gene expression can be detected 14 .…”

Section: Box 1 Combinatorial Control Of Gene Status and Resistance Tomentioning

confidence: 99%

“…Similarly to egg-NT, reprogramming in synkaryons is hard to analyse because of the cell divisions that follow the fusion of nuclei and cytoplasms. By contrast, heterokaryons allow the description and analysis of the events that accompany the reprogramming of a somatic cell nucleus in the absence of cell division.An alternative to cell fusion is the exposure of somatic cells to embryonic stem (ES) cell extract 14 . Under these conditions, cell division-dependent reprogramming of gene expression is also observed (FIG.…”

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confidence: 99%

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Mechanisms of nuclear reprogramming by eggs and oocytes: a deterministic process?

Jullien

Pasque²,

Halley-Stott³

et al. 2011

Nat Rev Mol Cell Biol

105

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Differentiated cells can be experimentally reprogrammed back to pluripotency by nuclear transfer, cell fusion or induced pluripotent stem cell technology. Nuclear transfer and cell fusion can lead to efficient reprogramming of gene expression. The egg and oocyte reprogramming process includes the exchange of somatic proteins for oocyte proteins, the post-translational modification of histones and the demethylation of DNA. These events occur in an ordered manner and on a defined timescale, indicating that reprogramming by nuclear transfer and by cell fusion rely on deterministic processes.The remarkable stability of cell differentiation under normal conditions can be reversed experimentally by nuclear transfer, cell fusion and induced pluripotent stem (iPS) cell technology [1][2][3][4][5] . This provides an opportunity to generate pluripotent embryonic cells from adult cells of the same individual and hence opens the possibilit y of cell replacement without the need for immunosuppression.iPS cell technology makes use of the overexpression of transcription factors (FIG. 1a) and has been extensively reviewed, so it is not discussed in detail [6][7][8][9] . To generate entirely unrelated cell types by iPS cell technology, treated cells must be grown for multiple cell divisions over a long period of time (up to 3 weeks). By contrast, nuclear transfer and cell fusion do not involve the overexpression of new genes, and instead make use of natura components present in eggs and some early embryos to initiate new transcription.There are two kinds of nuclear transfer experiments: egg-NT involves the transfer of a single somatic nucleus to an unfertilize d enucleated egg (in both mammals and amphibians) 1 (FIG. 1b); and ooc-NT involves the transplantation of multiple somatic cell nuclei into the germinal vesicle (the nucleus) of a growing meiotic prophase amphibian oocyte (an immature egg) 10 (FIG. 1c). Note that the terms egg and oocyte refer to different developmental stages in amphibians and mammals: amphibian eggs are in metaphase II of meiosis, which is equivalent to mouse metaphase II stage oocytes, whereas their immediate precursors, oocytes, are blocked in meiotic prophase I, which is equivalent to mouse germinal vesicle stage oocytes.© 2011 Macmillan Publishers Limited. All rights reserved Correspondence to J.B.G.j.gurdon@gurdon.cam.ac.uk. Competing interests statementThe authors declare no competing financial interests. There are important differences between the two types of nuclear transfer experimen t. Extensive cell division takes place in egg-NT experiments, and functional new cell types appear as the nuclear transplant embryo develops. By contrast, in ooc-NT experiments, no new cell types are formed, and neither the oocyte nor the introduced nuclei divide, but there is a direct transition from nuclei of differentiated cells to reprogrammed nuclei that transcribe pluripotency genes. Analysis of the mechanism of reprogramming (which involves transcription of pluripotency and other genes) in egg-NT expe...

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“…There is great interest in cellular reprogramming to pluripotency because this allows us to generate patient-specific pluripotent stem cells, differentiate them into functional cells such as neurons and cardiomyocytes, and use them to study human diseases or replace degenerated and damaged tissue. Several approaches have been developed to reprogram somatic cells to pluripotent state, including somatic cell nuclear transfer (SCNT) (Wilmut et al, 1997), fusing with ESCs or EGCs, or exposing them to ESC or EC extracts (Taranger et al, 2005). In 2006, an important breakthrough was achieved by Takahashi and Yamanaka (Takahashi and Yamanaka, 2006).…”

Section: Introductionmentioning

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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Induction of Dedifferentiation, Genomewide Transcriptional Programming, and Epigenetic Reprogramming by Extracts of Carcinoma and Embryonic Stem Cells

Cited by 252 publications

References 53 publications

Combined effects of the two reciprocal t(4;11) fusion proteins MLL·AF4 and AF4·MLL confer resistance to apoptosis, cell cycling capacity and growth transformation

Combined effects of the two reciprocal t(4;11) fusion proteins MLL·AF4 and AF4·MLL confer resistance to apoptosis, cell cycling capacity and growth transformation

Mechanisms of nuclear reprogramming by eggs and oocytes: a deterministic process?

Mechanism and methods to induce pluripotency

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