scholarly journals Cell Fusion-Mediated Tissue Regeneration as an Inducer of Polyploidy and Aneuploidy

2020 ◽  
Vol 21 (5) ◽  
pp. 1811 ◽  
Author(s):  
Jessica Dörnen ◽  
Mareike Sieler ◽  
Julian Weiler ◽  
Silvia Keil ◽  
Thomas Dittmar

The biological phenomenon of cell fusion plays a crucial role in several physiological processes, including wound healing and tissue regeneration. Here, it is assumed that bone marrow-derived stem cells (BMSCs) could adopt the specific properties of a different organ by cell fusion, thereby restoring organ function. Cell fusion first results in the production of bi- or multinucleated hybrid cells, which either remain as heterokaryons or undergo ploidy reduction/heterokaryon-to-synkaryon transition (HST), thereby giving rise to mononucleated daughter cells. This process is characterized by a merging of the chromosomes from the previously discrete nuclei and their subsequent random segregation into daughter cells. Due to extra centrosomes concomitant with multipolar spindles, the ploidy reduction/HST could also be associated with chromosome missegregation and, hence, induction of aneuploidy, genomic instability, and even putative chromothripsis. However, while the majority of such hybrids die or become senescent, aneuploidy and genomic instability appear to be tolerated in hepatocytes, possibly for stress-related adaption processes. Likewise, cell fusion-induced aneuploidy and genomic instability could also lead to a malignant conversion of hybrid cells. This can occur during tissue regeneration mediated by BMSC fusion in chronically inflamed tissue, which is a cell fusion-friendly environment, but is also enriched for mutagenic reactive oxygen and nitrogen species.

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1465
Author(s):  
Mareike Sieler ◽  
Julian Weiler ◽  
Thomas Dittmar

The phenomenon of cancer cell–cell fusion is commonly associated with the origin of more malignant tumor cells exhibiting novel properties, such as increased drug resistance or an enhanced metastatic capacity. However, the whole process of cell–cell fusion is still not well understood and seems to be rather inefficient since only a certain number of (cancer) cells are capable of fusing and only a rather small population of fused tumor hybrids will survive at all. The low survivability of tumor hybrids is attributed to post-fusion processes, which are characterized by the random segregation of mixed parental chromosomes, the induction of aneuploidy and further random chromosomal aberrations and genetic/epigenetic alterations in daughter cells. As post-fusion processes also run in a unique manner in surviving tumor hybrids, the occurrence of novel properties could thus also be a random event, whereby it might be speculated that the tumor microenvironment and its spatial habitats could direct evolving tumor hybrids towards a specific phenotype.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lucile Delespaul ◽  
Caroline Gélabert ◽  
Tom Lesluyes ◽  
Sophie Le Guellec ◽  
Gaëlle Pérot ◽  
...  

AbstractCell–cell fusion is a physiological process that is hijacked during oncogenesis and promotes tumour evolution. The main known impact of cell fusion is to promote the formation of metastatic hybrid cells following fusion between mobile leucocytes and proliferating tumour cells. We show here that cell fusion between immortalized myoblasts and transformed fibroblasts, through genomic instability and expression of a specific transcriptomic profile, leads to emergence of hybrid cells acquiring dissemination properties. This is associated with acquisition of clonogenic ability by fused cells. In addition, by inheriting parental properties, hybrid tumours were found to mimic the histological characteristics of a specific histotype of sarcomas: undifferentiated pleomorphic sarcomas with incomplete muscular differentiation. This finding suggests that cell fusion, as macroevolution event, favours specific sarcoma development according to the differentiation lineage of parent cells.


Small groups of two to four fibroblasts at the periphery of outgrowths from cultured explants of chick embryo heart were isolated from their neighbours by sweeping away the nearby cells. The groups and the explants were left attached to the glass substrate, undisturbed. The behaviour of the isolated cells was photographically recorded during about 8 h of further culture. The cells of these groups dispersed, though not as a rule so far as to lose all mutual contacts, the dispersal being counterbalanced by the addition of new cells through mitosis. The accompanying changes in speed of locomotion, and the non-random nature of the spreading, are interpreted in terms of the effects of contacts between the cells. During the first four hours after isolation, but not thereafter, the cells of the groups on the average moved slowly away from the explant. Control groups in an intact outgrowth moved away faster and with no diminution of speed during the period of observation. The movement of the isolated groups can be partly accounted for by the tendency of cells to conserve for a time the direction of their movement before isolation; and by a strong reluctance of the isolated cells to move across the area, from which cells had been scraped away, that lay between the group and the explant. A new outgrowth of the residual sheet of cells still connected to the explant, however, advanced across this area, approaching and in most cases overhauling the isolated group. It is concluded that a chemotactic gradient around the explant is unlikely to play any significant part in the outward movement of fibroblasts from an explant in tissue culture. The cells of the isolated groups underwent an outburst of mitosis about 3 h after isolation. Mitoses in these relatively free cells are oriented in relation to the polarity of the cell before division. Locomotion of the daughter-cells tends to be faster than usual for at least 2 h after a cell divides.


2016 ◽  
Vol 4 (20) ◽  
pp. 3515-3525 ◽  
Author(s):  
Shirae K. Leslie ◽  
Anthony M. Nicolini ◽  
Gobalakrishnan Sundaresan ◽  
Jamal Zweit ◽  
Barbara D. Boyan ◽  
...  

Alginate microbeads incorporating adipose-derived stem cells (ASCs) have potential for delivering viable cells capable of facilitating tissue regeneration.


1981 ◽  
Vol 49 (1) ◽  
pp. 87-97
Author(s):  
D. Rohme

The dose response of Sendai virus-induced cell fusion was studied in 10 mammalian cell lines, comprising 5 continuous and 5 diploid cell lines originating from 5 species. The extent of fusion was calculated using a parameter directly proportional to the number of fusion events (t-parameter). At lower levels of fusion the dose response was found to be based on the same simple kinetic rules in all cell lines and was defined by the formula: t = FS. FAU/(I + FS. FAU), where FS (fusion sensitivity) is a cell-specific constant of the fusion rate and FAU (fusion activity units) is the virus dose. The FS potential of a cell line was determined as the linear regression coefficient of the fusion index (t/(I - t)) on the virus dose. At higher levels of fusion, when the fusion extent reached cell-line-specific maximal levels, the dose response was not as uniform. In general, and particularly in the cases of the diploid cell lines, these maximal levels were directly proportional to the FS potentials. Thus, it was concluded that the FS potential is the basic quantitative feature, which expresses the cellular fusion efficiency. The fact that FS varied extensively between cell lines, but at the same time apparently followed certain patterns (being higher in continuous compared to diploid cell lines and being related to the species of origin of the cells), emphasizes it biological significance as well as its possible usefulness in studies of the efficiency of various molecular interactions in the cell membrane/cytoskeleton system.


2021 ◽  
Vol 134 (4) ◽  
pp. jcs254029
Author(s):  
Yi-Chun Liao ◽  
Su Hao Lo

ABSTRACTTensins are a family of focal adhesion proteins consisting of four members in mammals (TNS1, TNS2, TNS3 and TNS4). Their multiple domains and activities contribute to the molecular linkage between the extracellular matrix and cytoskeletal networks, as well as mediating signal transduction pathways, leading to a variety of physiological processes, including cell proliferation, attachment, migration and mechanical sensing in a cell. Tensins are required for maintaining normal tissue structures and functions, especially in the kidney and heart, as well as in muscle regeneration, in animals. This Review discusses our current understanding of the domain functions and biological roles of tensins in cells and mice, as well as highlighting their relevance to human diseases.


1967 ◽  
Vol 34 (1) ◽  
pp. 97-110 ◽  
Author(s):  
Jesse E. Sisken ◽  
Elaina Wilkes

p-Fluorophenylalanine (PFPA), an analogue of phenylalanine which may be incorporated into proteins, increases the duration of mitosis. In the present experiments, based upon quantitative analyses of time-lapse cinemicrographic films, brief treatments of cells with PFPA are shown to affect the duration of metaphase in only those cells which enter division during or shortly after treatment. The offspring of cells with prolonged metaphases also tend to have prolonged metaphases. Analyses of the kinetics of the appearance of prolonged metaphases indicate that some protein specifically associated with mitosis is synthesized primarily during a period which corresponds closely to G2. The manner in which the defect is passed on to daughter cells indicates that the protein involved is conserved and reutilized by daughter cells for their subsequent divisions. Comparable experiments performed with low concentrations of puromycin indicate that the major effect of PFPA is due to its incorporation into protein rather than its ability to inhibit protein synthesis. The fact that puromycin-induced effects can also be passed on to daughter cells is interpreted to mean that cells make only specific amounts of some mitosis-associated proteins and that if a cell "inherits" a deficiency in such protein it is not able to compensate for the deficiency.


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