课题组研究人员以单核多组测序为主题，同时分析唐氏综合征前额叶皮层在出生后早期发育期间的基因表达和染色质可及性，这是突触发生、神经成熟和发育性神经免疫相互作用的关键时期。他们的发现揭示了染色质可及性和基因表达的普遍失调，包括代谢和突触途径的缺陷，少突胶质细胞谱系的进展，以及明显的神经炎症特征。该研究团队在大脑发育的关键阶段展示了唐氏综合征神经病理学的分子图谱，突出了趋同的神经发育和神经退行性途径，并为唐氏综合征相关神经炎症的潜在靶向治疗提供了信息。
据了解，唐氏综合症是一种导致智力残疾的遗传性疾病，其特征是运动、认知和语言发育的早发性延迟。这些神经发育障碍的分子机制仍然知之甚少。
附：英文原文
Title: Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex
Author: Ryan D. Risgaard, Kalpana Hanthanan Arachchilage, Sara A. Knaack, Masoumeh Hosseini, Rachel J. Chen, Pubudu Kumarage, Danielle K. Schmidt, Xiang Huang, Jie Sheng, Carlos J. Wang, Elisa Giusti, Shuang Liu, Su-Chun Zhang, Daifeng Wang, Anita Bhattacharyya, Andre M. M. Sousa
Issue&Volume: 2026-04-23
Abstract: Down syndrome is a genetic condition that causes intellectual disability and is characterized by early-onset delays in motor, cognitive, and language development. The molecular mechanisms underlying these neurodevelopmental impairments remain poorly understood. We used single-nucleus multiomic sequencing to simultaneously profile gene expression and chromatin accessibility in the Down syndrome prefrontal cortex during early postnatal development, a critical period for synaptogenesis, neural maturation, and developmental neuroimmune interactions. Our findings reveal widespread dysregulation of chromatin accessibility and gene expression, with deficits spanning metabolic and synaptic pathways, oligodendrocyte lineage progression, and a pronounced neuroinflammatory signature. We present a molecular atlas of Down syndrome neuropathology at a critical stage of brain development, highlighting convergent neurodevelopmental and neurodegenerative pathways and informing potential targeted therapies for Down syndrome–associated neuroinflammation.
DOI: aea1549
Source: https://www.science.org/doi/10.1126/science.aea1549