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Increasing cell size remodels the proteome and promotes senescence

ABSTRACT: Cell size is tightly controlled in healthy tissues, but it is unclear how deviations in cell size affect cell physiology. To address this, we measured how the proteome changes with cell size. Protein concentration changes are widespread and predicted by subcellular localization, size-dependent mRNA concentrations, and protein turnover. As proliferating cells grow larger, concentration changes associated with cellular senescence are increasingly pronounced, suggesting that large size may be a cause rather than just a consequence of cell senescence. Consistent with this hypothesis, larger cells are prone to replicative, DNA damage-, and CDK4/6i-induced senescence. Size-dependent changes to the proteome, including those associated with senescence, are not observed when an increase in cell size is accompanied by an increase in ploidy. Together, our findings show how cell size could impact many aspects of cell physiology through remodeling the proteome and provide a rationale for cell size control and polyploidization.

ORGANISM(S): Homo sapiens Drosophila melanogaster

PROVIDER: GSE208348 | GEO | 2022/08/01

REPOSITORIES: GEO

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Project description:Polyploidization as the consequence of 2n gamete formation is a prominent mechanism in plant evolution. Studying its effects on the genome and its expression has both basic and applied interest. We crossed two diploid (2n=2x=16) M. sativa plants, a subsp. falcata seed parent and a coerulea x falcata pollen parent that produce a mixture of n and 2n eggs and pollen, respectively. Such cross produced full-sib diploid and tetraploid (2n=4x=32) progenies, the latter being the result of bilateral sexual polyploidization (BSP). These unique materials allowed us to investigate the effects of BSP, and separating the effect of intraspecific hybridization from those of polyploidization by comparing 2x with 4x full sib progeny plants. SSR marker segregation demonstrated tetrasomic inheritance for all chromosomes but one, demonstrating that these neotetraploids are true autotetraploids. BSP brought about increased biomass, earlier flowering, higher seed set and weight, larger leaves with larger cells. Microarray analyses with M. truncatula gene chips showed that several hundred genes, related to diverse metabolic functions, changed their expression level as a consequence of polyploidization. In addition, cytosine methylation increased in 2x but not in 4x hybrids. Our results indicate that sexual polyploidization induce significant transcriptional novelty, possibly mediated in part by DNA methylation, and phenotypic novelty that can be at the base of improved adaptation and reproductive success of tetraploid M. sativa with respect to its diploid progenitor. These polyploidy-induced changes may have promoted the adoption of tetraploid alfalfa in agriculture. Gene expression analysis of leaves at the vegetative stage of two Medicago sativa genotypes (PG-F9 and 12P) compared with three F1 diploid lines and three F1 tetraploid lines originating from crossing PG-F9 x 12P. Three biological replicates were taken for each sample, resulting in a total of twenty-four samples.

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Increasing cell size remodels the proteome and promotes senescence

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