ScRNAseq and TCRseq of tumor infiltrating CD8 T cells from samples
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE302214 | GEO | 2025/07/14
REPOSITORIES: GEO
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Project description:scRNAseq and TCRseq of tumor infiltrating CD8 T cells from samples
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Project description:The mammalian central nervous system (CNS) and its retina are susceptible to age-related patholgoies, resulting in progressive, irreversible diseases like glaucoma and age-related macular degeneration (AMD), which are increasingly prevalent with rising life expectancy. Currently, there are no targeted long-term therapies to prevent vision loss. The short lived African turquoise killifsh (Nothobranchius furzeri, GRZ-AD) is a valuable genetic model for ageing studies, displaying rapid ageing phenotypes within its four to six-month lifespan. Our investigation on the molecular consequences of ageing in the retina, employing scRNA-sequencing, shows a a comprehensive overview of the cellular heterogeneity of the killifish retina, uncovering age-related gene expression changes specific to certain retinal cell populations.
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Project description:Transcriptional profiling of human control and Néstor-Guillermo Progeria Syndrome (NGPS) mesenchymal stem cells (MSCs). Somatic cell reprogramming involves rejuvenation of adult cells and relies on the ability to erase age-associated molecular marks. Accordingly, reprogramming efficiency declines with ageing, and age-associated features such as genetic instability, cell senescence or telomere shortening negatively affect this process. However, the regulatory mechanisms that constitute age-associated barriers for cell reprogramming remain largely unknown. Here, by using cells from patients with premature ageing, we demonstrate that NF-κB activation is a critical barrier for the generation of induced pluripotent stem cells (iPSCs) in ageing. We show that NF-κB repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-κB hyperactivation impairs generation of iPSCs by eliciting reprogramming repressors DOT1L and YY1, reinforcing cell senescence signals and down-regulating pluripotency genes. We also show that genetic and pharmacological NF-κB inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Néstor-Guillermo Progeria Syndrome (NGPS) and Hutchinson-Gilford Progeria Syndrome (HGPS) patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo ameliorates the accelerated ageing phenotype and extends lifespan in a progeroid animal model. Collectively, our results provide evidence for a novel role of NF-κB in the control of cell fate transitions and reinforce the interest of studying age-associated molecular impairments to implement cell reprogramming methodologies, and to identify new targets of rejuvenation strategies. Control and NGPS MSCs were differentiated into bone in the presence or absence of sodium salicylate. Total RNA was extracted and global gene expression was analyzed.
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