Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1078754 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28027658_1.fastq.gz | Fastqsanger.gz | |||
| SRR28027658_2.fastq.gz | Fastqsanger.gz | |||
| SRR28027659_1.fastq.gz | Fastqsanger.gz | |||
| SRR28027659_2.fastq.gz | Fastqsanger.gz | |||
| SRR28027660_1.fastq.gz | Fastqsanger.gz |
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Project description:Understanding thyroid aging is essential for deciphering its physiological and pathological alterations, yet the causal relationship between aging and thyroid disease remains poorly characterized. We conducted a comprehensive proteomic analysis of 6109 thyroid tissues across ages 8-87 from 22 clinical centers (retrospective and prospective cohorts). Using a machine learning-based biological aging clock, we quantified accelerated aging phenotypes in pathological tissues, including benign and malignant nodules. We identified linear and non-linear age-associated proteins and pathways related to metabolism, immune response, and extracellular matrix organization remodeling, with critical transitions observed during the third, sixth, and eighth decades. Cross-species analysis of mouse and monkey tissues uncovered conserved aging markers. Intervention studies suggested that low-protein diets delay thyroid aging in mice, and therapeutic drug screening identified potential anti-tumor candidates. This study establishes the first organ-specific thyroid aging clock, linking tumorigenesis to accelerated aging, and proposing dietary interventions for thyroid longevity.
2025-11-04 | PXD061183 | Pride
Project description:Apolipoprotein E4 (APOE4) is the leading genetic risk factor for Alzheimer’s disease. While most studies examine the role of APOE4 in aging, APOE4 causes persistent changes in brain structure as early as infancy and is associated with altered functional connectivity that extends beyond adolescence. Here, we used human induced pluripotent stem cell (iPSC) derived cortical and ganglionic eminence organoids (COs and GEOs) to examine APOE4’s influence during cortical development of excitatory and inhibitory neurons. We show that APOE4 reduced cortical neurons and increased glia by promoting gliogenic transcriptional programs. In contrast, increased proliferation and differentiation of GABAergic progenitors resulted in early and persistent increases in GABAergic neurons. Multi-electrode array recordings in assembloids revealed that APOE4 disrupted neural network function resulting in heightened excitability and synchronicity. Together, our data provides new insights on how APOE4 influences cortical neurodevelopmental processes and network formation.
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Project description:Recent findings suggest that the human APOE epsilon 4 allele protects against non-alcoholic fatty liver disease, while APOE epsilon 3 promotes hepatic steatosis and steatohepatitis. We performed an untargeted proteome analysis of the liver and identified a great number of proteins differently expressed in obese APOE3 and APOE4 mice. The majority of the proteins up-regulated in APOE3 can be grouped to inflammation and damage-associated response, cytoskeleton and lipid storage. In contrast, those proteins that are up-regulated in APOE4 can be related to intermediate filament modifications, biotransformation and amino acid metabolism. Results of the targeted quantitative RT-PCR and Western blot experiments contribute to the overall finding that APOE3 promotes hepatic steatosis, inflammatory- and damage-associated response signaling and fibrosis in the liver of obese mice. One of the proteins that were up-regulated in obese as well as lean APOE4 compared to APOE3 mice is parvulin 14 (Pin4). Up-regulation of parvulin 14 may be involved in the protection against fatty liver disease evident in the presence of APOE4.
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Project description:FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these data sets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental principles underlying aging in animals. Whole-transcriptome profiling of daf-16/FoxO isoform-specific deletion mutants in the long-lived daf-2(e1370) background. Included are daf-16 wild-type, daf-16 null mutation, daf-16a/f mutation, two independent daf-16a mutations, and daf-16f mutation. N2 wild-type controls are also included.
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