Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3542 - 3542

Published: March 24, 2022

DNA replication during cell proliferation is ‘vertical’ copying, which reproduces an initial amount of genetic information. Polyploidy, results from whole-genome duplication, a fundamental complement to vertical copying. Both organismal and polyploidy can emerge via premature cycle exit or cell-cell fusion, the latter giving rise polyploid hybrid organisms epigenetic hybrids somatic cells. Polyploidy-related increase in biological plasticity, adaptation, stress resistance manifests evolution, development, regeneration, aging, oncogenesis, cardiovascular diseases. Despite prevalence nature importance for medicine, agri- aquaculture, processes mechanisms underlying these features largely remain unknown. The evolutionarily conserved include activation transcription, response stress, damage hypoxia, induction programs morphogenesis, unicellularity, longevity, suggesting that common confer adaptive viability, cells organisms. By increasing polyploidization provide survival under stressful conditions where diploid cannot survive. However, it occurs at expense specific function, thus promoting developmental programming adult diseases risk cancer. Notably, genes arising evolutionary are heavily involved cancer other Ploidy-related changes gene expression presumably originate chromatin modifications derepression bivalent genes. provided evidence elucidates role carcinogenesis, may contribute development new strategies regeneration preventing

Language: Английский

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Polyploid tubular cells: a shortcut to stress adaptation

Kidney International, Journal Year: 2024, Volume and Issue: 105(4), P. 709 - 716

Published: Jan. 9, 2024

Tubular epithelial cells (TC) compose the majority of kidney parenchyma and play fundamental roles in maintaining homeostasis. Like other tissues, mostly immature TC with progenitor capabilities are able to replace lost during injury via clonal expansion differentiation. In contrast, differentiated lack this capacity. However, as is frequently exposed toxic injuries, evolution positively selected a response program that endows maintain residual function injury. Recently, we others have described polyploidization TC, mechanism augment remnant after an by rapid hypertrophy. Polyploidy condition characterized more than two complete sets chromosomes. Polyploid often display increased functional capacity generally resilient stress evidenced being conserved across many plants eukaryote species from flies mammals. Here, discuss occurrence polyploidy different contexts conditions how integrates into existing concepts cell responses Collectively, aim at stimulating acquisition novel knowledge field well accelerating translation basic clinical sphere.

Language: Английский

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Whole-genome doubling in tissues and tumors

Trends in Genetics, Journal Year: 2023, Volume and Issue: 39(12), P. 954 - 967

Published: Sept. 14, 2023

Language: Английский

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Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 9691 - 9691

Published: Aug. 26, 2022

Polyploid cells demonstrate biological plasticity and stress adaptation in evolution; development; pathologies, including cardiovascular diseases, neurodegeneration, cancer. The nature of ploidy-related advantages is still not completely understood. Here, we summarize the literature on molecular mechanisms underlying adaptive features. Polyploidy can regulate gene expression via chromatin opening, reawakening ancient evolutionary programs embryonality. Chromatin opening switches genes with bivalent domains that promote rapid induction response to signals or morphogenesis. Therefore, stress-associated polyploidy activate Myc proto-oncogenes, which further opening. Moreover, proto-oncogenes trigger polyploidization de novo accelerate genome accumulation already polyploid cells. As a result these cooperative effects, increase ability search for states cellular through regulatory network rewiring. This manifested epigenetic associated traits stemness, unicellularity, flexible energy metabolism, complex system DNA damage protection, combining primitive error-prone unicellular repair pathways, advanced error-free multicellular damage-buffering ability. These three features be considered important components increased adaptability evidence presented here contribute understanding resistance ploidy may useful development new methods prevention treatment oncological diseases.

Language: Английский

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The antagonistic relationship between apoptosis and polyploidy in development and cancer

Seminars in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 156, P. 35 - 43

Published: June 16, 2023

Language: Английский

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Integrating the Study of Polyploidy Across Organisms, Tissues, and Disease

Annual Review of Genetics, Journal Year: 2024, Volume and Issue: 58(1), P. 297 - 318

Published: Sept. 4, 2024

Polyploidy is a cellular state containing more than two complete chromosome sets. It has largely been studied as discrete phenomenon in either organismal, tissue, or disease contexts. Increasingly, however, investigation of polyploidy across disciplines coalescing around common principles. For example, the recent Across Tree Life meeting considered contribution both organismal evolution over millions years and tumorigenesis much shorter timescales. Here, we build on this newfound integration with unified discussion organisms, cells, disease. We highlight how at multiple biological scales, thus eliminating outdated mindset its specialization. Additionally, discuss rules that are likely to all instances polyploidy. With increasing appreciation pervasive nature displays fascinating commonalities diverse contexts, inquiry related important topic rapidly becoming unified.

Language: Английский

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Conserved chamber-specific polyploidy maintains heart function in Drosophila

Development, Journal Year: 2023, Volume and Issue: 150(16)

Published: Aug. 1, 2023

Developmentally programmed polyploidy (whole-genome duplication) of cardiomyocytes is common across evolution. Functions such are essentially unknown. Here, in both Drosophila larvae and human organ donors, we reveal distinct levels cardiac chambers. In Drosophila, differential growth cell cycle signal sensitivity leads the heart chamber to reach a higher ploidy/cell size relative aorta chamber. Cardiac ploidy-reduced animals exhibit reduced size, stroke volume output, acceleration circulating hemocytes. These phenotypes mimic cardiomyopathies. Our results identify productive likely conserved roles for chambers suggest that precise ploidy sculpt many developing tissues. findings cardiomyocyte impact efforts block developmental improve injury recovery.

Language: Английский

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Surviving the Storm: The Role of Poly‐ and Depolyploidization in Tissues and Tumors

Advanced Science, Journal Year: 2024, Volume and Issue: 11(24)

Published: April 17, 2024

Abstract Polyploidization and depolyploidization are critical processes in the normal development tissue homeostasis of diploid organisms. Recent investigations have revealed that polyaneuploid cancer cells (PACCs) exploit this ploidy variation as a survival strategy against anticancer treatment for repopulation tumors. Unscheduled polyploidization chromosomal instability PACCs enhance malignancy resistance. However, their inability to undergo mitosis causes catastrophic cellular death most PACCs. Adaptive ploid reversal mechanisms, such multipolar mitosis, centrosome clustering, meiosis‐like division, amitosis, counteract lethal outcome drive relapse. The purpose work is focus on induced by cytotoxic therapy, highlighting latest discoveries dynamics physiological pathological contexts. Specifically, emphasizing role “poly‐depolyploidization” tumor progression, aim identify novel therapeutic targets or paradigms combating diseases associated with aberrant ploidies.

Language: Английский

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An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of the Drosophila wing disc

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(9), P. e1011387 - e1011387

Published: Sept. 3, 2024

A programmed developmental switch to G / S endocycles results in tissue growth through an increase cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute cancer. Much remains unknown, however, about how these iECs affect growth. Using the D . melanogaster wing disc as model, we find that populations of initially size then subsequently undergo a heterogenous arrest causes severe undergrowth. acquired DNA damage and activated Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant not eliminated from epithelium. Instead, entered JNK-dependent reversible senescent-like arrest. Senescent promoted division diploid neighbors, this compensatory proliferation did rescue Our study has uncovered unique attributes their effects on have important implications for understanding roles

Language: Английский

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Diacylglycerol kinase alpha regulates post-hepatectomy liver regeneration

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol to generate phosphatidic acid, which plays important roles in intracellular signal transduction. DGKα is reportedly associated with progression of tumors, including hepatocellular carcinomas, but its relationship liver regeneration has not been examined. The purpose this research elucidate the role regeneration. Here, we provide a detailed examination C57BL/6 wild-type and knockout (KO) mice subjected 70% partial hepatectomy (70% PH) modeling, survival rates, hematological marker gene expression levels, histological analyses factors related Following PH, KO produce higher levels hepatobiliary enzymes have incidence jaundice compared mice, death rate ~ 40%. Furthermore, they exhibit impaired glycogen lipid consumption, low energy charge, hepatocyte hypertrophy disorder, accompanied by significantly reduced proliferating cell nuclear antigen cyclin D. We conclude that key molecule post-PH process may potential as therapeutic target for acceleration

Language: Английский

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