Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells.

By M. Tada, Yousuke Takahama, Kuniya Abe, N. Nakatsuji, T. Tada. Current Biology, 2001

917 citations recorded by the source corpus.

The resetting of a somatic epigenotype to a totipotential state has been demonstrated by successful animal cloning, via transplantation of somatic nuclei into enucleated oocytes. We have established an experimental system, which reproduces the nuclear reprogramming of somatic cells in vitro by fusing adult thymocytes with embryonic stem (ES) cells. Analysis of the lymphoid-cell-specific V-(D)-J DNA rearrangement of the T cell receptor and immunoglobin genes shows that the ES cells have hybridized with differentiated cells. In these ES cell hybrids, the inactivated X chromosome derived from a female thymocyte adopts some characteristics of an active X chromosome, including early replication timing and unstable Xist transcription. We also found that an Oct4-GFP transgene, which is normally repressed in thymocytes, is reactivated 48 hr after cell fusion. The pluripotency of the ES-thymocyte hybrid cells is shown in vivo, since they contribute to all three primary germ layers of chimeric embryos. The somatic DNA methylation pattern of the imprinted H19 and Igf2r genes is maintained in these hybrids, unlike hybrids between ES and EG (embryonic germ) cells in which the differential methylation is erased. Thus, ES cells have the capacity to reset certain aspects of the epigenotype of somatic cells to those of ES cells.

Subfields: Molecular Biology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/54113404219a9bbff9a0f6e9638d7a5f2c2e83c8

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Citations in the corpus

Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. (2008, background): “Even though epigenetic reprogramming of a somatic genome to an embryonic state by nuclear transfer or fusion of ES cells with somatic cells has become a widely used procedure in various mammalian species over the last decade (Cowan et al., 2005; Kato et al., 1998; Polejaeva et al., 2000; Tada et al.”
Nanog Is the Gateway to the Pluripotent Ground State (2009, neutral): “…also be created outside the embryo by reprogramming somatic cells, either by fusion with pre-existing pluripotent cells (Miller and Ruddle, 1976; Tada et al., 1997, 2001; Takagi et al., 1983) or, more compellingly, by transfection with regulatory transcription factors (Takahashi and Yamanaka,…”
Changing potency by spontaneous fusion (2002, neutral): “Hybrids produced by electrofusion of ES cells with thymocytes have similarly been found to exhibit ES cell characteristics”
Nuclear reprogramming to a pluripotent state by three approaches (2010, background): “Tada and colleagues then showed that somatic cells can acquire a pluripotent state after being fused with ES cell”
Strategies and new developments in the generation of patient-specific pluripotent stem cells. (2007, background): “Consistent with this model, even partially reprogrammed Fbx15-iPS cells show hyperacetylated histones in the promoter regions of several ES cell-specific genes (Takahashi and Yamanaka, 2006).”
Epigenetic reprogramming and induced pluripotency (2009, background): “Another crucial observation for reprogramming studies was that EC, ES and EG cells can reprogram other somatic cells when fused with them, generating pluripotent tetraploid hybrid cells (Cowan et al., 2005; Miller and Ruddle, 1976; Tada et al., 1997; Tada et al., 2001).”
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. (2006, background): “Somatic cells can be reprogrammed by transferring their nuclear contents into oocytes (Wilmut et al., 1997) or by fusion with ES cells (Cowan et al., 2005; Tada et al., 2001), indicating that unfertilized eggs and ES cells contain factors that can confer totipotency or pluripotency to somatic cells.”
Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. (2007, background): “Reprogramming of a somatic genome by nuclear transfer or cell fusion is accompanied by epigenetic changes such as DNA demethylation of pluripotency genes at their promoter regions (Cowan et al., 2005; Tada et al., 2001 ).”
Senescence impairs successful reprogramming to pluripotent stem cells. (2009, result): “Similar results can be obtained by fusion with mES cells (Tada et al., 2001) and hES cells (Cowan”
Induced pluripotency: history, mechanisms, and applications. (2010, background): “However, all of the pluripotent cell lines tested so far (ESCs, ECCs, and EGCs) have been shown to induce pluripotency in somatic cells after cellular fusion, demonstrating that they harbor dominant reprogramming activities (Tada et al. 1997, 2001; Cowan et al. 2005).”
In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state (2007, critical): “This important study left a number of questions unresolved: (1) although iPS cells were pluripotent they were not identical to ES cells (for example, iPS cells injected into blastocysts generated abnormal chimaeric embryos that did not survive to term); (2) gene expression profiling revealed major d”