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http://dx.doi.org/10.1016/j.stemcr.2023.04.009 | DOI Listing |
Mol Ther Methods Clin Dev
June 2025
Precision Safety, Pharma Product Development, Roche Innovation Center Basel, CH-4070 Basel, Switzerland.
Adeno-associated virus (AAV) vectors are widely used in gene therapy, particularly for liver-targeted treatments. However, predicting human-specific outcomes, such as transduction efficiency and hepatotoxicity, remains challenging. Reliable models are urgently needed to bridge the gap between preclinical studies and clinical applications.
View Article and Find Full Text PDFCell Rep
September 2025
Department of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA; Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Un
Neurodevelopmental disorders often impair multiple cognitive domains. For instance, a genetic epilepsy syndrome might cause seizures due to cortical hyperexcitability and present with memory impairments arising from hippocampal dysfunction. This study examines how a single disorder differentially affects distinct brain regions using induced pluripotent stem cell (iPSC)-derived cortical- and hippocampal-ganglionic eminence assembloids to model developmental and epileptic encephalopathy 13, a condition arising from gain-of-function mutations in the SCN8A gene encoding the sodium channel Nav1.
View Article and Find Full Text PDFJ Clin Invest
September 2025
Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, United Kingdom.
Understanding the genetic causes of diseases affecting pancreatic β cells and neurons can give insights into pathways essential for both cell types. Microcephaly, epilepsy and diabetes syndrome (MEDS) is a congenital disorder with two known aetiological genes, IER3IP1 and YIPF5. Both genes encode proteins involved in endoplasmic reticulum (ER) to Golgi trafficking.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Neuroscience, The Scripps Research Institute, San Diego, CA 92037.
Microglia regulate neuronal circuit plasticity. Disrupting their homeostatic function has detrimental effects on neuronal circuit health. Neuroinflammation contributes to the onset and progression of neurodegenerative diseases, including Alzheimer's disease (AD), with several microglial activation genes linked to increased risk for these conditions.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
State Key Laboratory of Membrane Biology, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Although clinical research has revealed microglia-related inflammatory and immune responses in bipolar disorder (BD) patient brains, it remains unclear how microglia contribute to the pathogenesis of BD. Here, we demonstrated that Serinc2 is associated with susceptibility to BD and showed a reduced expression in BDII patient plasma, which correlated with the disease severity. Using induced pluripotent stem cell (iPSC) models of sporadic and familial BDII patients, we found that Serinc2 expression showed deficits in iPSC-derived microglia-like cells, resulting in decreased synaptic pruning.
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