Genome-Wide Reprogramming in Hybrids of Somatic Cells and Embryonic Stem Cells

Ambrosi, Dominic J.; Tanasijevic, Borko; Kaur, Anupinder; Obergfell, Craig; O’Neill, Rachel J.; Krueger, Winfried; Rasmussen, Theodore P.

doi:10.1634/stemcells.2006-0532

Cited by 57 publications

(54 citation statements)

References 30 publications

(36 reference statements)

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“…the pluripotent phenotype becomes differentiated to a somatic-cell phenotype (Shimazaki et al, 1993) in a unidirectional process. Ambrosi et al showed that Journal of Cell Science 122 (22) the gene-expression profile of the fusion-hybrid cells is similar, but not identical, to that of the pluripotent cell partner (Ambrosi et al, 2007). Having assessed the transcriptional status of 36,601 transcripts encoded within the mouse genome, they categorized the genes in seven major clusters according to gene-expression patterns.…”

Section: Discussionmentioning

confidence: 99%

“…That is, pluripotent cells effectively reprogram somatic cells, abolishing the gene-expression patterns of the somatic cell and resetting the gene-expression profile to that of the pluripotent state. However, the gene-expression profile of the fusion-hybrid cells is similar, but not identical, to that of the pluripotent cell-fusion partner, indicating that fusion-induced reprogramming is a unidirectional process that occurs concomitantly with the incomplete reprogramming of certain genes (Ambrosi et al, 2007). Therefore, fusion-induced reprogramming does not necessarily result in the complete genetic reprogramming of somatic cells to a phenotype identical to that of the pluripotent cell-fusion partner.…”

Section: Introductionmentioning

confidence: 93%

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Reprogramming ofXistagainst the pluripotent state in fusion hybrids

Tae

Han

Gentile

et al. 2009

Journal of Cell Science

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The fusion of somatic cells with pluripotent cells results in the generation of pluripotent hybrid cells. Because the `memory' of somatic cells seems to be erased during fusion-induced reprogramming, genetic reprogramming is thought to be a largely unidirectional process. Here we show that fusion-induced reprogramming, which brings about the formation of pluripotent hybrids, does not always follow a unidirectional route. Xist is a unique gene in that it is reprogrammed to the state of somatic cells in fusion-induced pluripotent hybrids. In hybrids formed from the cell fusion of embryonal carcinoma cells (ECCs) with male neural stem cells (mNSCs), the Xist gene was found to be reprogrammed to the somatic cell state, whereas the pluripotency-related and tissue-specific marker genes were reprogrammed to the pluripotent cell state. Specifically, Xist is not expressed in hybrids, because the `memory' of the somatic cell has been retained (i.e. mNSCs do not exhibit Xist expression) and that of the pluripotent cell erased (i.e. inactivation of the partially active Xist gene of ECCs, complete methylation of the Xist region). The latter phenomenon is induced by male, but not by female, NSCs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Reprogramming ofXistagainst the pluripotent state in fusion hybrids

Tae

Han

Gentile

et al. 2009

Journal of Cell Science

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“…Apart from oocytes, embryonic germ (EG) cells and embryonic stem cells (ESC) also contain factors that can reprogram somatic cell nuclei, as fusion of these cells with somatic cells creates tetraploid hybrids wherein silencing and activation of genes on somatic chromosomes occurs [5]. Although transcriptional differences exist between ESC and ESC/EG cell-somatic cell hybrids [6], the latter can generate embryoid bodies (EBs) and teratomas and contribute to chimeras when injected into the blastocyst [7,8]. The activation of the pluripotency-associated transcription factor (TF) Oct4 can also be achieved through the introduction of cellfree extracts from ESC and embryonic carcinoma (EC) cells, although full reprogramming to pluripotency has not been shown [9].…”

Section: Introductionmentioning

confidence: 99%

Concise Review: Culture Mediated Changes in Fate and/or Potency of Stem Cells

2011

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Although Gurdon demonstrated already in 1958 that the nucleus of intestinal epithelial cells could be reprogrammed to give rise to adult frogs, the field of cellular reprogramming has only recently come of age with the description by Takahashi and Yamanaka in 2006, which defined transcription factors can reprogram fibroblasts to an embryonic stem cell-like fate. With the mounting interest in the use of human pluripotent stem cells and culture-expanded somatic stem/progenitor cells, such as mesenchymal stem cells, increasing attention has been given to the effect of changes in the in vitro microenvironment on the fate of stem cells. These studies have demonstrated that changes in culture conditions may change the potency of pluripotent stem cells or reprogram adult stem/progenitor cells to endow them with a broader differentiation potential. The mechanisms underlying these fate and potency changes by ex vivo culture should be further investigated and considered when designing clinical therapies with stem/progenitor cells. STEM CELLS

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“…This provided a good indication that EC nuclear pluripotency is not abolished in the presence of a differentiated genome (Miller and Ruddle, 1976). Differentiation into derivatives of the ectoderm, mesoderm and endoderm was later confirmed when teratoma and embryoid bodies were derived from hybrid cells made from somatic and ESCs (Ambrosi et al, 2007;Cowan et al, 2005;Tada et al, 2003;Terada et al, 2002;Yu et al, 2006). When hybrid cells resulting from the fusion of thymocytes with either embryonic germ cells (EGCs) or ESCs were injected into mouse embryos they contributed to the three lineages of the resulting chimera at the embryonic stage (Tada et al, 1997;Tada et al, 2001).…”

Section: By Cell Fusionmentioning

confidence: 84%

“…Thus, sets of genes are expressed at similar levels in hybrid and somatic cells, but differently in ESCs, suggesting incomplete resetting of the somatic genome (Ambrosi et al, 2007;Cowan et al, 2005).…”

Section: Cell Fusionmentioning

confidence: 99%

Faithful reprogramming to pluripotency in mammals - what does nuclear transfer teach us?

Maruotti

Jouneau²,

Renard³

2010

Int. J. Dev. Biol.

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Nuclear reprogramming toward pluripotency has been now achieved either in vivo by somatic cell nuclear transfer into the ooplasm of an enucleated egg, or in vitro by three different approaches, namely cell fusion, treatment with cell extracts and more recently, forced expression of a reduced set of defined transcription factors. This last technique has expanded our view of genome plasticity with important applied perspectives in regenerative biomedicine. Because of their ease of generation, induced pluripotent stem cells represent a major hope in the field of regenerative medicine. However, the extent to which such an in vitro induced pluripotency can be considered to be equivalent to embryonic-derived pluripotency remains undetermined and also largely dependent on how pluripotency is assessed. Here, we provide an overwiew of the data published in the recent literature on the ability of each of the above techniques to reprogram somatic nuclei into pluripotent embryonic-like nuclei. These data support the view that even though nuclear transfer is technically demanding, it remains a fast and efficient means for a systematic derivation of bona fide embryonic stem cells from somatic donor cells. We conclude that nuclear transfer has still much to teach us about faithful nuclear reprogramming to pluripotency.

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Genome-Wide Reprogramming in Hybrids of Somatic Cells and Embryonic Stem Cells

Abstract: ABSTRACT

Cited by 57 publications

References 30 publications

Reprogramming ofXistagainst the pluripotent state in fusion hybrids

Reprogramming ofXistagainst the pluripotent state in fusion hybrids

Concise Review: Culture Mediated Changes in Fate and/or Potency of Stem Cells

Faithful reprogramming to pluripotency in mammals - what does nuclear transfer teach us?

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