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Single-nucleus multi-omics identifies shared and distinct pathways in Pick's and Alzheimer's disease

2 weeks 3 days ago
The study of transcriptomic and epigenomic variations in neurodegenerative diseases, particularly tauopathies like Pick's disease (PiD) and Alzheimer's disease (AD), offers insights into their underlying regulatory mechanisms. Here, we identified critical regulatory changes driving disease progression, revealing potential therapeutic targets. Our comparative analyses uncovered disease-enriched noncoding regions and genome-wide transcription factor (TF) binding differences, linking them to target...
Zechuan Shi

iPEX enables micrometre-resolution deep spatial proteomics via tissue expansion

2 weeks 3 days ago
The number of spatial omics technologies being developed is increasing¹. However, a missing tool is one that can locate proteins in tissues in an untargeted manner at high spatial resolution and coverage. Here we present in situ imaging proteomics via expansion (iPEX), which integrates isotropic tissue magnification² with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging. iPEX provides scalable spatial resolution down to the micrometre scale and substantially...
Fengxiang Wang

circHERC1-A telomerase activator

2 weeks 3 days ago
Telomerase, crucial for maintaining telomere integrity and genomic stability, is typically silenced in somatic cells with advancing age. In this study, we identify circHERC1 as a regulator of telomerase reverse transcriptase (TERT) transcription. Specifically, circHERC1 binds to the TERT promoter, facilitating the recruitment of RNA polymerase II and c-Fos, thereby activating TERT expression. Notably, circHERC1 expression exhibits a decline with age, which correlates with reduced telomerase...
Yumeng Cui

Liver-directed AAV gene therapy in mice corrects glycogen storage disease type IX γ2

2 weeks 3 days ago
Glycogen storage disease (GSD) type IX γ2 is a rare inborn error of metabolism where a defect in glycogenolysis leads to the inability to break down glycogen in the liver. Patients with GSD IX γ2 develop hypoglycemia and advanced liver disease, placing them at risk for liver transplantation. This study evaluates the efficacy of liver-directed AAV gene therapy in a murine model of GSD IX γ2. Phkg2^(-/-) mice underwent treatment with AAV gene therapy (AAV9-LSP-mPhkg2, 5 × 10^(12) vg/kg,...
Rebecca A Gibson

Aging and immunity

2 weeks 3 days ago
Time marches endlessly on … but what does that mean for the immune system? Here, investigators discuss how aging impacts the immune response and how immune cells can shape the aging process, with broader implications for modifying immunity to improve not only longevity but also health span.
Christoph A Thaiss