Reprogramming of Somatic Cells Towards Pluripotency by Cell Fusion

Author(s):  
Andrzej R. Malinowski ◽  
Amanda G. Fisher
Keyword(s):  
Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 490
Author(s):  
Krystyna Żyżyńska-Galeńska ◽  
Agnieszka Bernat ◽  
Anna Piliszek ◽  
Jolanta Karasiewicz ◽  
Ewa Szablisty ◽  
...  

The phenomenon of the reprogramming of terminally differentiated cells can be achieved by various means, like somatic cell nuclear transfer, cell fusion with a pluripotent cell, or the introduction of pluripotency genes. Here, we present the evidence that somatic cells can attain the expression of pluripotency markers after their introduction into early embryos. Mouse embryonic fibroblasts introduced between blastomeres of cleaving embryos, within two days of in vitro culture, express transcription factors specific to blastocyst lineages, including pluripotency factors. Analysis of donor tissue marker DNA has revealed that the progeny of introduced cells are found in somatic tissues of foetuses and adult chimaeras, providing evidence for cell reprogramming. Analysis of ploidy has shown that in the chimaeras, the progeny of introduced cells are either diploid or tetraploid, the latter indicating cell fusion. The presence of donor DNA in diploid cells from chimaeric embryos proved that the non-fused progeny of introduced fibroblasts persisted in chimaeras, which is evidence of reprogramming by embryonic niche. When adult somatic (cumulus) cells were introduced into early cleavage embryos, the extent of integration was limited and only cell fusion-mediated reprogramming was observed. These results show that both cell fusion and cell interactions with the embryonic niche reprogrammed somatic cells towards pluripotency.


2008 ◽  
Vol 16 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Hiroyuki Matsumura ◽  
Takashi Tada

The cells of the body do not normally engage in sex. Nor is it easy to see that sexual activity would greatly benefit them. For sex is ultimately merely a device to facilitate the accumulation in a single individual of favourable mutations occurring separately in different individuals; and since the cells in the body are, at least in large part, genetically identical, the advantages to be gained by genetic exchange are obviously limited. In recent years, however, a technique has been devised that imposes a form of artificial sexuality on somatic cells, and it has been found that somatic cells of widely different genetic constitutions can be induced to undergo genetic amalgamation and exchange. A few years ago, Professor Hayes, in a Leeuwenhoek Lecture (Hayes 1966) described how sex in bacteria is mediated by an infectious particle which produces a change in the cell wall of the ‘male’ bacterium that enables it to make intimate contact with the ‘female’ bacterium. A connexion is then established between the cytoplasms of the two bacteria and through this connexion transfer of genetic material may take place. The imposition of sexuality on somatic cells is achieved by a mechanism which, viewed superficially, is reminiscent of bacterial conjugation. An animal virus, whose normal mode of entry into the cell appears to involve fusion between the viral membrane and the cell membrane, is used to facilitate fusion between the cell membranes of contiguous cells (Okada 1958; Harris & Watkins 1965). Cytoplasmic bridges are thus established which eventually determine the complete coalescence of the cytoplasms of adjacent cells (Schneeberger & Harris 1966). In this way multinucleated cells are formed which contain various numbers of nuclei, and different kinds of nuclei if cells of different kinds are brought together (Harris, Watkins, Ford & Schoefl 1966). The virus now commonly used to produce cell fusion is the Sendai virus, a member of the parainfluenza group of myxoviruses, although many other viruses can achieve the same effect. Unlike the sex particle in bacteria, however, Sendai virus will produce fusion of somatic cells even after its nucleic acid has been destroyed (Okada & Tadokoro 1962; Neff & Enders 1968); the viral envelope is all that is required for this effect. The standard reagent for inducing cell fusion is Sendai virus inactivated by large doses of ultraviolet light or by appropriate treatment with β -propriolactone.


2013 ◽  
Vol 24 (2) ◽  
pp. 267-280 ◽  
Author(s):  
T. J. Looney ◽  
L. Zhang ◽  
C.-H. Chen ◽  
J. H. Lee ◽  
S. Chari ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Nicholas A. Kouris ◽  
Jeremy A. Schaefer ◽  
Masato Hatta ◽  
Brian T. Freeman ◽  
Timothy J. Kamp ◽  
...  

Mesenchymal stem cells (MSCs) spontaneously fuse with somatic cellsin vivo, albeit rarely, and the fusion products are capable of tissue-specific function (mature trait) or proliferation (immature trait), depending on the microenvironment. That stem cells can be programmed, or somatic cells reprogrammed, in this fashion suggests that stem cell fusion holds promise as a therapeutic approach for the repair of damaged tissues, especially tissues not readily capable of functional regeneration, such as the myocardium. In an attempt to increase the frequency of stem cell fusion and, in so doing, increase the potential for cardiac tissue repair, we expressed the fusogen of the vesicular stomatitis virus (VSV-G) in human MSCs. We found VSV-G expressing MSCs (vMSCs) fused with cardiomyocytes (CMs) and these fusion products adopted a CM-like phenotype and morphologyin vitro.In vivo, vMSCs delivered to damaged mouse myocardium via a collagen patch were able to home to the myocardium and fuse to cells within the infarct and peri-infarct region of the myocardium. This study provides a basis for the investigation of the biological impact of fusion of stem cells with CMsin vivoand illustrates how viral fusion proteins might better enable such studies.


2011 ◽  
Vol 13 (4) ◽  
pp. 331-344 ◽  
Author(s):  
Pollyanna Agnes Tat ◽  
Huseyin Sumer ◽  
Daniele Pralong ◽  
Paul John Verma

Author(s):  
Carolyn A. Larabell ◽  
David G. Capco ◽  
G. Ian Gallicano ◽  
Robert W. McGaughey ◽  
Karsten Dierksen ◽  
...  

Mammalian eggs and embryos contain an elaborate cytoskeletal network of “sheets” which are distributed throughout the entire cell cytoplasm. Cytoskeletal sheets are long, planar structures unlike the cytoskeletal networks typical of somatic cells (actin filaments, microtubules, and intermediate filaments), which are filamentous. These sheets are not found in mammalian somatic cells nor are they found in nonmammalian eggs or embryos. Evidence that they are, indeed, cytoskeletal in nature is derived from studies demonstrating that 1) the sheets are retained in the detergent-resistant cytoskeleton fraction; 2) there are no associated membranes (determined by freeze-fracture); and 3) the sheets dissociate into filaments at the blastocyst stage of embryogenesis. Embedment-free sections of hamster eggs viewed at 60 kV show sheets running across the egg cytoplasm (Fig. 1). Although this approach provides excellent global views of the sheets and their reorganization during development, the mechanism of image formation for embedment-free sections does not permit evaluation of the sheets at high resolution.


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