Colonic epithelial and immune cells from young and aged mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE288290 | GEO | 2026/05/15
REPOSITORIES: GEO
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Project description:Aging is associated with a decline in the regenerative capacity of many tissues. Central to this decline is a complex interplay between inflammation and stem cell function. How these two processes are linked and influence regenerative capacity remains unclear. Here, we undertake a comprehensive assessment of age-related changes in the mouse small and large intestines at single-cell resolution.
2026-05-15 | GSE288291 | GEO
Project description:Aging hampers the regenerative potential of intestinal epithelium across species including humans, yet the underlying causes remain elusive. Here, using proteomic and metabolomic profiling of intestinal tissues together with functional assays, we characterized the temporal dynamics of regeneration following injury induced by 5-fluorouracil, a commonly used chemotherapeutic agent. Comparison of regeneration dynamics in mice of different ages revealed the emergence of proteostasis stress and increased levels of polyamines following injury exclusively in old epithelia. We show that delayed regeneration is an intrinsic feature of aged epithelial cells that display reduced protein synthesis and accumulation of ubiquitylated proteins. Inhibition of the polyamine pathway in vivo further delays regeneration in old mice, while its activation by dietary intervention or supplementation of polyamines is sufficient to enhance the regenerative capacity of aged intestines. Our findings highlight promising epithelial targets for interventions aimed at tackling the decline in tissue repair mechanisms associated with aging.
2025-06-23 | MSV000098282 | MassIVE
Project description:Aging hampers the regenerative potential of intestinal epithelium across species including humans, yet the underlying causes remain elusive. Here, using proteomic and metabolomic profiling of intestinal tissues together with functional assays, we characterized the temporal dynamics of regeneration following injury induced by 5-fluorouracil, a commonly used chemotherapeutic agent. Comparison of regeneration dynamics in mice of different ages revealed the emergence of proteostasis stress and increased levels of polyamines following injury exclusively in old epithelia. We show that delayed regeneration is an intrinsic feature of aged epithelial cells that display reduced protein synthesis and accumulation of ubiquitylated proteins. Inhibition of the polyamine pathway in vivo further delays regeneration in old mice, while its activation by dietary intervention or supplementation of polyamines is sufficient to enhance the regenerative capacity of aged intestines. Our findings highlight promising epithelial targets for interventions aimed at tackling the decline in tissue repair mechanisms associated with aging.
2025-06-23 | MSV000098281 | MassIVE
Project description:Ageing is associated with changes in the cellular composition of the immune system. During ageing, hematopoietic stem and progenitor cells (HSPCs) that produce immune cells are thought to decline in their regenerative capacity. However, HSPC function has been mostly assessed using transplantation assays, and it remains unclear how HSPCs age in the native bone marrow niche. To address this issue, we present a novel in situ single cell lineage tracing technology to quantify the clonal composition and cell production of single cells in their native niche. Our results demonstrate that a pool of HSPCs with unequal output maintains myelopoiesis through overlapping waves of cell production throughout adult life. During ageing, the increased frequency of myeloid cells is explained by greater numbers of HSPCs contributing to myelopoiesis, rather than increased myeloid output of individual HSPCs. Strikingly, the myeloid output of HSPCs remained remains constant over time despite accumulating significant transcriptomic changes throughout adulthood. Together, these results show that, unlike emergency myelopoiesis post-transplantation, aged HSPCs in their native microenvironment do not functionally decline in their regenerative capacity. This repository contains single-cell RNA sequencing datasets of hematopoietic stem and progenitor cells from young and aged mice associated with this study
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Project description:Aging reduces the regenerative capacity of the intestinal epithelium in different species including humans. The causes of delayed regeneration in the elderly remain unclear. Here, we used proteomic and metabolomic profiling of intestinal tissues together with functional assays to characterize the dynamics of regeneration following injury induced by 5-fluorouracil, a commonly used chemotherapeutic agent. Comparison of regeneration dynamics in mice of different ages revealed emergence of a proteostasis stress signature and increased levels of polyamines following injury exclusively in old epithelia. Mechanistically, we show that delayed regeneration is a cell-intrinsic feature of old epithelial cells that display reduced protein synthesis and accumulation of ubiquitylated proteins. We demonstrate that an intervention based on dietary restriction followed by re-feeding prior to injury elevates intracellular polyamine levels, alleviates proteostasis stress and restores the regenerative capacity of the old intestines. Our work provides novel targets and strategies to improve intestinal regeneration in the elderly.
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Project description:In this study, we performed single-cell RNA sequencing (scRNA-seq) on MAIT cells extracted from the intestines of young and aged mice. For each age group, MAIT cells from five individual mice were pooled before sequencing.
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