scholarly journals Blocking cell fusion inhibits age-induced polyploidy and maintains epithelial organization in Drosophila

2021 ◽  
Author(s):  
Ari S Dehn ◽  
Navdeep Gogna ◽  
Patsy M Nishina ◽  
Vicki P Losick
Keyword(s):  
Cell Growth ◽  
Cell Fusion ◽  
Polyploid Cell ◽  
Cellular Organization ◽  
Pattern Dystrophy ◽  
Multinucleated Cells ◽  
Tissue Organization ◽  
Age Related ◽  
Tissue Area ◽  
Nuclear Ploidy

A characteristic of normal aging and age-related diseases is the remodeling of a tissue's cellular organization through polyploid cell growth. Polyploidy arises from an increase in nuclear ploidy or the number of nuclei per cell. However, it is not known whether age-induced polyploidy is an adaption to stressors or a precursor to degeneration. Here, we find that the adult fruit fly's abdominal epithelium becomes polyploid with age through generation of large multinucleated cells that make up more than 40% of the tissue area. The syncytia arise by cell fusion, not endomitosis. Epithelial multinucleation is also a characteristic of macular degeneration, including Ctnna1tvrm5, a mouse model for pattern dystrophy. Similarly, we find that the knockdown of alpha-catenin enhances multinucleation in the fly epithelium. We further show that age-induced polyploidy can be suppressed by inhibiting cell fusion revealing a means to maintain tissue organization in older animals.

scholarly journals Wound-induced polyploidization is dependent on integrin-yki signaling

Biology Open ◽  
2020 ◽  
pp. bio.055996
Author(s):  
Rose Besen-McNally ◽  
Kayla J. Gjelsvik ◽  
Vicki P. Losick
Keyword(s):  
Wound Healing ◽  
Cell Growth ◽  
Cell Fusion ◽  
Focal Adhesion ◽  
Tissue Repair ◽  
Cell Number ◽  
Polyploid Cell ◽  
Tissue Mass ◽  
Polyploid Cells ◽  
Adhesion Complex

A key step in tissue repair is to replace lost or damaged cells. This occurs via two strategies: restoring cell number through proliferation or increasing cell size through polyploidization. Studies in Drosophila and vertebrates have demonstrated that polyploid cells arise in adult tissues, at least in part, to promote tissue repair and restore tissue mass. However, the signals that cause polyploid cells to form in response to injury remain poorly understood. In the adult Drosophila epithelium, wound-induced polyploid cells are generated by both cell fusion and endoreplication, resulting in a giant polyploid syncytium. Here, we identify the integrin focal adhesion complex as an activator of wound-induced polyploidization. Both integrin and focal adhesion kinase are upregulated in the wound-induced polyploid cells and are required for Yorkie induced endoreplication and cell fusion. As a result, wound healing is perturbed when focal adhesion genes are knocked down. These findings show that conserved focal adhesion signaling is required to initiate wound-induced polyploid cell growth.

Studies on Chemically Induced Cell Fusion

1972 ◽  
Vol 10 (3) ◽  
pp. 769-787
Author(s):  
Q. F. AHKONG ◽  
F. C. CRAMP ◽  
D. FISHER ◽  
J. I. HOWELL ◽  
J. A. LUCY
Keyword(s):  
Aqueous Solution ◽  
Cell Fusion ◽  
Plasma Membranes ◽  
Mouse Fibroblast ◽  
Nuclear Membranes ◽  
Multinucleated Cells ◽  
Large Numbers ◽  
Chemically Induced ◽  
Complete Disintegration ◽  
Unstable Plasma

Hen erythrocytes that were fixed after treatment with lysolecithin in aqueous solution for 30 s at 37 °C showed evidence of bridge formation between adjacent lysed cells. Generally, the homokaryons that were produced using lysolecithin in this way contained large numbers of nuclei. These giant syncytia had damaged nuclear membranes and unstable plasma membranes; complete disintegration of the syncytia occurred within 1 min of adding lysolecithin to the erythrocytes. In order to localize the action of lysolecithin, the fusing agent was incorporated into microdroplets of lipid. Cell fusion following the addition of lysolecithin in an aqueous glyceridelecithin emulsion was slower than with lysolecithin in aqueous solution, taking 10-30 min, and it was accompanied by considerably less damage to the plasma and nuclear membranes. The fused erythrocytes, which usually contained only two or three nuclei, lysed slowly during the 45 min following fusion, and lysis could be arrested by cooling the fused cells. The plasma membranes of lysed, multinucleated cells remained intact at 37°C for at least 90 h. Mouse fibroblast-hen erythrocyte heterokaryons formed with the aid of the emulsion were more stable than those produced with lysolecithin in solution, but the hybrid cells nevertheless had damaged subcellular organelles. Viable clones of hybrid mouse-hamster fibroblast cells were obtained using the emulsion although, possibly owing to reduced viability of the lysolecithin-treated cells, only at twice the frequency of spontaneously produced hybrids.

Somatic mutations in single human cardiomyocytes demonstrate accelerated age-related DNA damage and cell fusion

2020 ◽  
Author(s):  
Christopher Walsh ◽  
Sangita Choudhury ◽  
August Huang ◽  
Junho Junho Kim ◽  
Katherine Morillo ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Excision Repair ◽  
Single Nucleotide Variants ◽  
Mutational Signatures ◽  
Human Cardiomyocytes ◽  
Age Related ◽  
Lineage Tree ◽  
Dividing Cells ◽  
Heart Muscle Cells ◽  
Genetic Compensation

Abstract The accumulation of somatic DNA mutations is a hallmark of aging in many dividing cells and contributes to carcinogenesis. Here we survey the landscape of somatic single-nucleotide variants (sSNVs) in heart muscle cells (cardiomyocytes) which normally do not proliferate but often become polyploid with age. Using single-cell whole-genome sequencing we analyzed sSNVs from 48 single cardiomyocytes from 10 healthy individuals (ages 0.4 - 82 yrs.). Cardiomyocyte sSNVs increased strikingly with age, at rates faster than reported in many dividing cells, or in non-dividing neurons. Analysis of nucleotide substitution patterns revealed age-related “clock-like” mutational signatures resembling those previously described. However, cardiomyocytes showed distinct mutational signatures that are rare or absent in other cells, implicating failed nucleotide excision repair of oxidative damage and defective mismatch repair (MMR) during aging. A lineage tree of cardiomyocytes, constructed using clonal sSNVs, revealed that some tetraploid (10%) and most cardiomyocytes with higher ploidy (>60%) derive from distinct clonal origins, implicating cell fusion as a mechanism contributing to many polyploid cardiomyocytes. Since age-accumulated sSNVs create dozens of damaging exonic mutations, cell fusion to form multiploid cardiomyocytes may represent an evolutionary mechanism of cellular genetic compensation that minimizes complete knockout of essential genes during aging. The rates and patterns of accumulation of cardiac mutations provide a paradigm to understand the influence of genomic aging on age-related heart disease.

scholarly journals Virus-Mediated Cell-Cell Fusion

2020 ◽  
Vol 21 (24) ◽  
pp. 9644
Author(s):  
Héloïse Leroy ◽  
Mingyu Han ◽  
Marie Woottum ◽  
Lucie Bracq ◽  
Jérôme Bouchet ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Fusion Proteins ◽  
Target Cells ◽  
Special Focus ◽  
Human Pathogens ◽  
General Process ◽  
Tissue Organization ◽  
Donor Cells ◽  
Infected Cells ◽  
Cell Cell

Cell-cell fusion between eukaryotic cells is a general process involved in many physiological and pathological conditions, including infections by bacteria, parasites, and viruses. As obligate intracellular pathogens, viruses use intracellular machineries and pathways for efficient replication in their host target cells. Interestingly, certain viruses, and, more especially, enveloped viruses belonging to different viral families and including human pathogens, can mediate cell-cell fusion between infected cells and neighboring non-infected cells. Depending of the cellular environment and tissue organization, this virus-mediated cell-cell fusion leads to the merge of membrane and cytoplasm contents and formation of multinucleated cells, also called syncytia, that can express high amount of viral antigens in tissues and organs of infected hosts. This ability of some viruses to trigger cell-cell fusion between infected cells as virus-donor cells and surrounding non-infected target cells is mainly related to virus-encoded fusion proteins, known as viral fusogens displaying high fusogenic properties, and expressed at the cell surface of the virus-donor cells. Virus-induced cell-cell fusion is then mediated by interactions of these viral fusion proteins with surface molecules or receptors involved in virus entry and expressed on neighboring non-infected cells. Thus, the goal of this review is to give an overview of the different animal virus families, with a more special focus on human pathogens, that can trigger cell-cell fusion.

scholarly journals Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells.

1988 ◽  
Vol 167 (2) ◽  
pp. 598-611 ◽  
Author(s):  
A McInnes ◽  
D M Rennick
Keyword(s):  
Bone Marrow ◽  
Inflammatory Response ◽  
Cell Fusion ◽  
Cell Cultures ◽  
Soft Agar ◽  
Interleukin 4 ◽  
Multinucleated Cells ◽  
Granulomatous Lesions

Giant multinucleated cells (GMCs) are associated with granulomatous lesions that form in response to various infectious and noninfectious agents. The present study shows that mouse IL-4 induces the in vitro formation of GMCs by factor-dependent bone marrow and alveolar monocytes via cell fusion. GMCs appear 2 d after incubation of cell cultures with 20 U/ml or more of IL-4. Anti-IL-4 mAbs block the appearance of GMCs in these cultures, indicating that IL-4 acts directly on monocytes to promote fusion and does not secondarily induce the production of other soluble fusion factors. In soft agar cultures, IL-4 also causes the aggregation of macrophages and diminishes their migration. The role of IL-4 in a granulomatous inflammatory response is discussed.

scholarly journals Barrier Activity in Candida albicans Mediates Pheromone Degradation and Promotes Mating

2007 ◽  
Vol 6 (6) ◽  
pp. 907-918 ◽  
Author(s):  
Dana Schaefer ◽  
Pierre Côte ◽  
Malcolm Whiteway ◽  
Richard J. Bennett
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Cell Growth ◽  
Cell Fusion ◽  
Aspartyl Protease ◽  
Wild Type ◽  
Pheromone Activity ◽  
Important Regulator ◽  
Mutant Cells ◽  
Type Strains

ABSTRACT Mating in Candida albicans and Saccharomyces cerevisiae is regulated by the secretion of peptide pheromones that initiate the mating process. An important regulator of pheromone activity in S. cerevisiae is barrier activity, involving an extracellular aspartyl protease encoded by the BAR1 gene that degrades the alpha pheromone. We have characterized an equivalent barrier activity in C. albicans and demonstrate that the loss of C. albicans BAR1 activity results in opaque a cells exhibiting hypersensitivity to alpha pheromone. Hypersensitivity to pheromone is clearly seen in halo assays; in response to alpha pheromone, a lawn of C. albicans Δbar1 mutant cells produces a marked zone in which cell growth is inhibited, whereas wild-type strains fail to show halo formation. C. albicans mutants lacking BAR1 also exhibit a striking mating defect in a cells, but not in α cells, due to overstimulation of the response to alpha pheromone. The block to mating occurs prior to cell fusion, as very few mating zygotes were observed in mixes of Δbar1 a and α cells. Finally, in a barrier assay using a highly pheromone-sensitive strain, we were able to demonstrate that barrier activity in C. albicans is dependent on Bar1p. These studies reveal that a barrier activity to alpha pheromone exists in C. albicans and that the activity is analogous to that caused by Bar1p in S. cerevisiae.

scholarly journals GTL1 keeps cell growth and nuclear ploidy under control

2012 ◽  
Vol 31 (24) ◽  
pp. 4483-4485 ◽  
Author(s):  
Elena Caro ◽  
Bénédicte Desvoyes ◽  
Crisanto Gutierrez
Keyword(s):  
Cell Growth ◽  
Nuclear Ploidy

Headless henipaviral receptor binding glycoproteins reveal key post-receptor binding contributions of the globular head and head/stalk interface in fusion promotion

2021 ◽  
Author(s):  
Yao Yu Yeo ◽  
David W. Buchholz ◽  
Amandine Gamble ◽  
Mason Jager ◽  
Hector C. Aguilar
Keyword(s):  
Cell Fusion ◽  
Receptor Binding ◽  
Viral Entry ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Wild Type ◽  
Emerging Viruses ◽  
Multinucleated Cells ◽  
Head Domain ◽  
Cell Cell

Cedar virus (CedV) is a nonpathogenic member of the Henipavirus (HNV) genus of emerging viruses, which includes the deadly Nipah (NiV) and Hendra (HeV) viruses. CedV forms syncytia, a hallmark of henipaviral and paramyxoviral infections and pathogenicity. However, the intrinsic fusogenic capacity of CedV relative to NiV or HeV remains unquantified. HNV entry is mediated by concerted interactions between the attachment (G) and fusion (F) glycoproteins. Upon receptor binding by the HNV G head domain, a fusion-activating G stalk region is exposed and triggers F to undergo a conformational cascade that leads to viral entry or cell-cell fusion. Here, we first demonstrated quantitatively that CedV is inherently significantly less fusogenic than NiV at equivalent G and F cell surface expression levels. We then generated and tested six headless CedV G mutants of distinct stalk C-terminal lengths, surprisingly revealing highly hyperfusogenic cell-cell fusion phenotypes 3 to 4-fold greater than wild-type CedV levels. Additionally, similarly to NiV, a headless HeV G mutant yielded a less pronounced hyperfusogenic phenotype compared to wild-type HeV. Further, coimmunoprecipitation and cell-cell fusion assays revealed heterotypic NiV/CedV functional G/F bidentate interactions, as well as evidence of HNV G head domain involvement beyond receptor binding or G stalk exposure. All evidence points to the G head/stalk junction being key to modulating HNV fusogenicity, supporting the notion that head domains play several distinct and central roles in modulating stalk domain fusion promotion. Further, this study exemplifies how CedV may help elucidate important mechanistic underpinnings of HNV entry and pathogenicity. IMPORTANCE The Henipavirus genus in the Paramyxoviridae family includes the zoonotic Nipah (NiV) and Hendra (HeV) viruses. NiV and HeV infections often cause fatal encephalitis and pneumonia, but no vaccines or therapeutics are currently approved for human use. Upon viral entry, Henipavirus infections yield the formation of multinucleated cells (syncytia). Viral entry and cell-cell fusion are mediated by the attachment (G) and fusion (F) glycoproteins. Cedar virus (CedV), a nonpathogenic henipavirus, may be a useful tool to gain knowledge on henipaviral pathogenicity. Here, using homotypic and heterotypic full-length and headless CedV, NiV, and HeV G/F combinations, we discovered that CedV G/F are significantly less fusogenic than NiV or HeV G/F, and that the G head/stalk junction is key to modulating cell-cell fusion, refining the mechanism of henipaviral membrane fusion events. Our study exemplifies how CedV may be a useful tool to elucidate broader mechanistic understanding for the important henipaviruses.

Pattern Dystrophies and Choroidal Neovascularization

2017 ◽  
pp. 313-320
Keyword(s):  
Visual Acuity ◽  
Choroidal Neovascularization ◽  
Middle Ages ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Subretinal Fluid ◽  
Age Related Macular Degeneration ◽  
Pattern Dystrophy ◽  
Good Visual Acuity ◽  
Age Related

Pattern dystrophies are hereditary dystrophies that come from retinal pigment epithelium and located in the macula. The diagnosis is usually made around the middle ages. Pigment accumulations in the macula and around the macula, are seen bilaterally and symmetrical in the beginning, are sub-divided depending on pigment scattering pattern. These are adult-onset foveomacular vitelliform dystrophy, butterfly-like pattern dystrophy, reticular pattern dystrophy, and fundus pulverulentus. Usually in patients with pattern dystrophy have good visual acuity, after progression central visual acuity lessens with RPE atrophy or choroidal neovascularization development. In choroidal neovascularization secondary to age-related macular degeneration there is no typical pigmentation in the macula. On the other hand, in choroidal neovascularization related to pattern dystrophy, hemorrhage, and intra/subretinal fluid do not exist. Today choroidal neovascularization prognosis, which is treated with intravitreal anti-VEGF injections, is quite good. At least, one eye of the patients has satisfactory vision. Sometimes, in especially patients with isolated pattern dystrophy, not hereditary, there may be spontaneous regression of choroidal neovascularization.

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