Reprogramming Mediated by Cell Fusion Technology

Serov, O. L.; Matveeva, N. M.; Хабарова, А. А.

doi:10.1016/b978-0-12-386035-4.00005-7

Cited by 11 publications

(6 citation statements)

References 127 publications

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“…Experiments using somatic cell nuclear transfer 46 , cell fusion 36 – 38 and extract-mediated 22 , 23 , 26 induction confirmed that pluripotent cells, similar to oocytes, contain a lot of unknown factors capable of affecting somatic cell reprogramming. Previous reports have shown the roles of ESC, embryonal carcinoma and EGC extracts on reprogramming by hybrids with somatic cells; notably, the roles of EGCs in epigenetic reprogramming trumped the others 36 , 47 , 48 . Derived from PGCs, EGCs harbor an epigenome similar to that of PGCs, which show a genome-wide reprogramming of DNA methylation 34 , 35 ; thus, EGCs might still contain demethylation factors and be better for reprogramming than ESCs.…”

Section: Discussionmentioning

confidence: 99%

Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells

Zhao

Feng

et al. 2018

Sci Rep

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Patient-specific induced pluripotent stem cells (iPSCs) have the potential to be useful in the treatment of human diseases. While prior studies have reported multiple methods to generate iPSCs, DNA methylation continues to limit the totipotency and reprogramming efficiency of iPSCs. Here, we first show the competency of embryonic germ cells (EGCs) as a reprogramming catalyst capable of effectively promoting reprogramming induced by four defined factors, including Oct4, Sox2, Klf4 and c-Myc. Combining EGC extracts with these four factors resulted in formation of more embryonic stem cell-like colonies than did factors alone. Notably, expression of imprinted genes was higher with combined induction than with factors alone. Moreover, iPSCs derived from the combined inductors tended to have more global hypomethylation. Our research not only provides evidence that EGC extracts could activate DNA demethylation and reprogram imprinted genes, but also establishes a new way to enhance reprogramming of iPSCs, which remains a critical safety concern for potential use of iPSCs in regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells

Zhao

Feng

et al. 2018

Sci Rep

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“…Low levels of pluripotent gene expression from the somatic partner are initiated in a proportion of heterokaryons and increase over a 3–4 day period before the parental nuclei fuse to generate hybrids (Pereira et al., 2008). This second step has been proposed to stabilize or “fix” newly acquired gene expression profiles, enabling the resulting tetraploid cells to generate pluripotent colonies (reviewed by Serov et al., 2011). Because the first step occurs in the absence of cell division, it has been generally assumed that DNA synthesis is not required to initiate reprogramming.…”

Section: Introductionmentioning

confidence: 99%

DNA Synthesis Is Required for Reprogramming Mediated by Stem Cell Fusion

Tsubouchi

Soza-Ried

Brown

et al. 2013

Cell

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SummaryEmbryonic stem cells (ESCs) can instruct the conversion of differentiated cells toward pluripotency following cell-to-cell fusion by a mechanism that is rapid but poorly understood. Here, we used centrifugal elutriation to enrich for mouse ESCs at sequential stages of the cell cycle and showed that ESCs in S/G2 phases have an enhanced capacity to dominantly reprogram lymphocytes and fibroblasts in heterokaryon and hybrid assays. Reprogramming success was associated with an ability to induce precocious nucleotide incorporation within the somatic partner nuclei in heterokaryons. BrdU pulse-labeling experiments revealed that virtually all successfully reprogrammed somatic nuclei, identified on the basis of Oct4 re-expression, had undergone DNA synthesis within 24 hr of fusion with ESCs. This was essential for successful reprogramming because drugs that inhibited DNA polymerase activity effectively blocked pluripotent conversion. These data indicate that nucleotide incorporation is an early and critical event in the epigenetic reprogramming of somatic cells in experimental ESC-heterokaryons.

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“…The most numerous group 1 comprises silenced and activated genes that dramatically change expression during the hybrid cell clone formation, consistent with the phenotype of a hybrid cell. The phenomenon of gene silencing and activation is typical for somatic cell reprogramming after fusion with ES cells 3 , 4 , 8 , 19 – 21 . Undoubtedly, these genes are responsible for the establishment of the phenotype of hybrid cells.…”

Section: Discussionmentioning

confidence: 99%

Alternative dominance of the parental genomes in hybrid cells generated through the fusion of mouse embryonic stem cells with fibroblasts

Matveeva

Fishman

Захарова

et al. 2017

Sci Rep

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For the first time, two types of hybrid cells with embryonic stem (ES) cell-like and fibroblast-like phenotypes were produced through the fusion of mouse ES cells with fibroblasts. Transcriptome analysis of 2,848 genes differentially expressed in the parental cells demonstrated that 34–43% of these genes are expressed in hybrid cells, consistent with their phenotypes; 25–29% of these genes display intermediate levels of expression, and 12–16% of these genes maintained expression at the parental cell level, inconsistent with the phenotype of the hybrid cell. Approximately 20% of the analyzed genes displayed unexpected expression patterns that differ from both parents. An unusual phenomenon was observed, namely, the illegitimate activation of Xist expression and the inactivation of one of two X-chromosomes in the near-tetraploid fibroblast-like hybrid cells, whereas both Xs were active before and after in vitro differentiation of the ES cell-like hybrid cells. These results and previous data obtained on heterokaryons suggest that the appearance of hybrid cells with a fibroblast-like phenotype reflects the reprogramming, rather than the induced differentiation, of the ES cell genome under the influence of a somatic partner.

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Reprogramming Mediated by Cell Fusion Technology

Cited by 11 publications

References 127 publications

Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells

Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells

DNA Synthesis Is Required for Reprogramming Mediated by Stem Cell Fusion

Alternative dominance of the parental genomes in hybrid cells generated through the fusion of mouse embryonic stem cells with fibroblasts

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