Ontology highlight
ABSTRACT:
PROVIDER: PRJNA706345 | ENA |
REPOSITORIES: ENA
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Project description:MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.
2018-11-28 | PXD011537 | Pride
Project description:mass spectrometry analysis of aged and adult hematopoietic stem cells, multipotent progenitors and oligopotent progenitors
2021-07-24 | PXD017442 | Pride
Project description:p53 Regulates Hematopoietic Stem Cell Quiescence
| PRJNA110049 | ENA
Project description:Prostaglandin E2 (PGE2) Enhances Aged Hematopoietic Stem Cell Function
| PRJNA729494 | ENA
Project description:Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity and differentiation-bias towards myeloid lineage. While, the molecular mechanism behind it remains not fully understood. In this study, we observed that the expression of pseudouridine (Ψ) synthase 10 is increased in aged hematopoietic stem and progenitor cells (HSPCs) and enforced PUS10 recapitulates the phenotype of aged HSCs, which is not achieved by its Ψ synthase activity. Consistently, we observed no difference of tRNA pseudouridylation profile between young and aged HSPCs. No significant alteration of hematopoietic homeostasis and HSC function is observed in young Pus10-/- mice, while aged Pus10-/-mice exhibit mild alteration of hematopoietic homeostasis and HSC function. Moreover, we observed that PUS10 is ubiquitinated by E3 ubiquitin ligase CRL4DCAF1 complex and the increase of PUS10 in aged HSPCs is due to aging-declined CRL4DCAF1-mediated ubiquitination degradation signaling. Taken together, this study for the first time evaluated the role of PUS10 in HSC aging and function, and provided novel insight for HSC rejuvenation and clinical application.
2023-05-13 | GSE213417 | GEO
Project description:Glycyrrhizic acid (GA) has numerous biological activities, but the mechanism by which it regulates the immune system and improves cognition in aged mice remains unclear. In this study, we analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice, and found that GA reduced senescence-induced increases in macrophages and neutrophils, and increased numbers of lymphoid lineage subpopulations specifically reduced by senescence. In vitro, GA significantly promoted differentiation of Lin-CD117+ hematopoietic stem cells toward lymphoid lineages, especially CD8+ T cells. Moreover, GA inhibited differentiation of CD4+ T cells and myeloid (CD11b+) cells by binding to the S100 calcium-binding protein 8 (S100A8). Overexpression of S100A8 in Lin- CD117+ hematopoietic stem cells enhanced cognition in aged mice and in immune reconstited severely immunodeficient B-NDG mice. Collectively, our results suggest that GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice.
2023-07-14 | GSE216599 | GEO
Project description:Glycyrrhizic acid (GA) has numerous biological activities, but the mechanism by which it regulates the immune system and improves cognition in aged mice remains unclear. In this study, we analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice, and found that GA reduced senescence-induced increases in macrophages and neutrophils, and increased numbers of lymphoid lineage subpopulations specifically reduced by senescence. In vitro, GA significantly promoted differentiation of Lin-CD117+ hematopoietic stem cells toward lymphoid lineages, especially CD8+ T cells. Moreover, GA inhibited differentiation of CD4+ T cells and myeloid (CD11b+) cells by binding to the S100 calcium-binding protein 8 (S100A8). Overexpression of S100A8 in Lin- CD117+ hematopoietic stem cells enhanced cognition in aged mice and in immune reconstited severely immunodeficient B-NDG mice. Collectively, our results suggest that GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice.
2023-07-14 | GSE216598 | GEO
Project description:A member of the nuclear receptors, retinoic acid-related orphan receptor a (RORa) is an important transcription factor for various biological processes including circadian rhythm, metabolic regulation, immune cell development and cancer. Here we found that RORa is important for intestinal homeostasis by negatively regulating the transcriptional activity of NF-kB, a major inflammatory regulator in intestinal epithelial cells. Intestinal Rora-deficient mice found were highly susceptible to DSS-induced injury. Transcriptome analysis showed that intestine-specific Rora deletion causes regulatory impairment of NF-kB signaling leading to excessive inflammatory responses. RORa specifically binds to the NF-kB target promoter and inhibits transcriptional activity for transcriptional repression of NF-kB activity via histone deacetylase 3 (HDAC3). Taken together, RORa plays a pivotal role in the homeostatic regulation of intestinal epithelial cells in inflammatory conditions. Therefore, therapeutic strategies designed to modulate RORa activity may be beneficial in the treatment of chronic inflammatory diseases such as Inflammatory bowel disease (IBD).
2019-09-30 | GSE121977 | GEO
