Functional T cells are capable of supernumerary cell division and longevity [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA878843 | ENA |
REPOSITORIES: ENA
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Project description:Functional T cells are capable of supernumerary cell division and longevity
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Project description:Functional T cells are capable of supernumerary cell division and longevity [ATAC-seq]
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Project description:Differentiated somatic mammalian cells putatively exhibit species-specific division limits that impede cancer but may constrain lifespans. To provide immunity, transiently stimulated CD8 T cells undergo unusually rapid bursts of numerous cell divisions, then form quiescent long-lived memory cells that remain poised to reproliferate in response to subsequent immunological challenges. Here, we addressed whether T cells are intrinsically constrained by chronological or cell division limits. We activated mouse T cells in vivo using acute heterologous-prime-boost-boost vaccinations, transferred expanded cells to new mice, and then repeated that process iteratively. Over a period of 10 years (greatly exceeding the mouse lifespan) and 51 successive immunizations, T cells remained competent to respond to vaccination. Cells did require sufficient rest between stimulation events. Despite demonstrating the potential to expand the starting population at least 10^40-fold, cells did not show loss of proliferation control and results were not due to contamination with young cells. Persistent stimulation by chronic infections or cancer can result in a well-described transcriptional program that results in T cell proliferative senescence, functional exhaustion, and death. We found that while iterative acute stimulations also induced sustained expression and epigenetic remodeling of common exhaustion markers, including PD-1 and Tox, these cells retained the capacity to proliferate, execute antimicrobial functions, and form quiescent memory cells. These observations provide a model to better understand memory cell differentiation, exhaustion, and aging, and show that functionally competent T cells can retain the potential for extraordinary population expansion and longevity well beyond their organismal lifespan.
2022-11-17 | GSE213060 | GEO
Project description:Differentiated somatic mammalian cells putatively exhibit species-specific division limits that impede cancer but may constrain lifespans. To provide immunity, transiently stimulated CD8 T cells undergo unusually rapid bursts of numerous cell divisions, then form quiescent long-lived memory cells that remain poised to reproliferate in response to subsequent immunological challenges. Here, we addressed whether T cells are intrinsically constrained by chronological or cell division limits. We activated mouse T cells in vivo using acute heterologous-prime-boost-boost vaccinations, transferred expanded cells to new mice, and then repeated that process iteratively. Over a period of 10 years (greatly exceeding the mouse lifespan) and 51 successive immunizations, T cells remained competent to respond to vaccination. Cells did require sufficient rest between stimulation events. Despite demonstrating the potential to expand the starting population at least 10^40-fold, cells did not show loss of proliferation control and results were not due to contamination with young cells. Persistent stimulation by chronic infections or cancer can result in a well-described transcriptional program that results in T cell proliferative senescence, functional exhaustion, and death. We found that while iterative acute stimulations also induced sustained expression and epigenetic remodeling of common exhaustion markers, including PD-1 and Tox, these cells retained the capacity to proliferate, execute antimicrobial functions, and form quiescent memory cells. These observations provide a model to better understand memory cell differentiation, exhaustion, and aging, and show that functionally competent T cells can retain the potential for extraordinary population expansion and longevity well beyond their organismal lifespan.
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2021-06-10 | PXD020440 |
Project description:Glucose as a source of energy is centrally important to our understanding of life. We investigated the cell division-quiescence behavior of the fission yeast Schizosaccharomyces pombe under a wide range of glucose concentrations (0-111 mM). The mode of S. pombe cell division under a microfluidic perfusion system was surprisingly normal under highly diluted glucose concentrations (5.6 mM, 1/20 of the standard medium, within human blood sugar levels). Division became stochastic, accompanied by a curious division-timing inheritance, in 2.2-4.4 mM glucose. A critical transition from division to quiescence occurred within a narrow range of concentrations (2.2-1.7 mM). Under starvation (1.1 mM) conditions, cells were mostly quiescent and only a small population of cells divided. Under fasting (0 mM) conditions, division was immediately arrested with a short chronological lifespan (16 h). When cells were first glucose starved prior to fasting, they possessed a substantially extended lifespan (∼14 days). We employed a quantitative metabolomic approach for S. pombe cell extracts, and identified specific metabolites (e.g. biotin, trehalose, ergothioneine, S-adenosyl methionine and CDP-choline), which increased or decreased at different glucose concentrations, whereas nucleotide triphosphates, such as ATP, maintained high concentrations even under starvation. Under starvation, the level of S-adenosyl methionine increased sharply, accompanied by an increase in methylated amino acids and nucleotides. Under fasting, cells rapidly lost antioxidant and energy compounds, such as glutathione and ATP, but, in fasting cells after starvation, these and other metabolites ensuring longevity remained abundant. Glucose-starved cells became resistant to 40 mM H(2)O(2) as a result of the accumulation of antioxidant compounds.
2017-07-06 | MTBLS316 | MetaboLights