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Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

ABSTRACT: Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

PROVIDER: PRJNA857893 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR18054318.fastq.gz	Fastqsanger.gz
	SRR18054319.fastq.gz	Fastqsanger.gz
	SRR18054320.fastq.gz	Fastqsanger.gz
	SRR18054321.fastq.gz	Fastqsanger.gz

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Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

Project description:Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

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Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

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Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

Project description:Antibody persistence frequently determines the longevity of immunity, yet the mechanisms that set antibody-producing plasma cell turnover rates are unestablished. While it is proposed that new plasma cells displace existing ones in competition for specialised survival niches, it is also possible that the spontaneous loss of existing plasma cells frees niches thereby creating opportunities for recruitment, possibilities with quite different implications for maximising antibody production and persistence. Here, using a genetic reporter to timestamp plasma cells, we define the distribution, phenotype, transcriptional program and population structure of long-lived plasma cells and calculate turnover dynamics. We show that the attributes of longevity are acquired and that turnover of long-lived plasma cells at homeostasis is unaffected by the absence of B cells, indicating that the mechanism of turnover is independent of competition. We propose that understanding plasma cell population dynamics may allow their manipulation to achieve specific outcomes.

2023-05-09 | GSE207979 | GEO

Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

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Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-05-09 | GSE207980 | GEO

Project description:Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

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wt vs daf-2 C. elegans protein turnover

Project description:Most aging hypotheses revolve around the accumulation of some sort of damage resulting in gradual physiological decline and ultimately death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend lifespan. However, lowering translational efficiency extends rather than shortens lifespan in C. elegans. We studied turnover of individual proteins in the conserved Insulin/Insulin-like Growth Factor (IGF-1) receptor mutant daf-2 by combining Stable Isotope Labeling by Nitrogen-15 in Caenorhabditis elegans and LC-MS/MS. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, while others remained unchanged, signifying that longevity is not supported by high protein turnover. This slow-down of protein turnover was most prominent for components of the translation machinery and mitochondria. In contrast, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged in daf-2. The slow-down of protein dynamics and decreased abundance of the translational machinery may point at the importance of anabolic attenuation in lifespan extension as suggested by the hyperfunction theory.

2016-09-27 | PXD002317 | Pride

Multiomics of GCN4-dependent replicative lifespan extension models reveals Gcn4 as a regulator of protein turnover in yeast

Project description:We have shown that multiple tRNA synthetase inhibitors can increase lifespan in both the nematode C. elegans and the budding yeast S. cerevisiae by acting through the conserved transcription factor Gcn4 (yeast) / ATF-4 (worms). To further understand the biology downstream of this conserved transcription factor in the yeast model system, we looked at two different yeast models known to have both upregulated Gcn4, and GCN4-dependent increased replicative lifespan. These two models are rpl31aΔ yeast, and yeast treated with the tRNA synthetase inhibitor borrelidin. We used both proteomic and RNAseq analysis of a block experimental design that included both of these models, to identify GCN4-dependent changes in these two longlived strains of yeast. Proteomic analysis of these yeast indicate that the longlived yeast have increased abundance of proteins involved in amino acid biosynthesis. RNASeq of these same yeast uncovered further regulation of protein turnover, identifying the differential expression of genes associated with both autophagy and with the ubiquitin proteasome system. The data presented here further underscore the important role that GCN4 and its orthologs play in the maintenance of protein homeostasis, which is itself an important hallmark of aging. Importantly, these changes could also have wider-ranging implications in the understanding and treatment of diseases of aging characterized by protein aggregation.

2023-11-11 | GSE242739 | GEO

Critical role of histone turnover in neuronal transcription and plasticity [RNA-seq]

Project description:Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation associated histone dynamics in the regulation of activity-dependent transcription, synaptic connectivity and behavior. We uncover a dramatic developmental profile of nucleosome occupancy across the lifespan of both rodents and humans, with the histone variant H3.3 accumulating to near saturating levels throughout the neuronal genome by mid-adolescence. Despite such accumulation, H3.3 containing nucleosomes remain highly dynamic–in a modification independent manner–to control neuronal- and glial- specific gene expression patterns throughout life. Manipulating H3.3 dynamics in both embryonic and adult neurons confirmed its essential role in neuronal plasticity and cognition. Our findings establish histone turnover as a critical, and previously undocumented, regulator of cell-type specific transcription and plasticity in mammalian brain. All RNA-seq samples were generated to test the impact of neuronal activity/adult physiological plasticity on histone turnover turnover mediated alterations in mRNA expression in the central nervous system. This was tested in cultured neurons and astrocytes, and embryonic/adult brain tissues

2015-06-23 | E-GEOD-69807 | biostudies-arrayexpress

Intrinsically nitroimidazole resistant Mycobacterium tuberculosis

Project description:Intrinsically nitroimidazole resistant Mycobacterium tuberculosis

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