Developmental dynamics of the single nucleus regulatory landscape of pig hippocampus
作者机构:State Key Laboratory of Pig Genetic Improvement and Production TechnologyJiangxi Agricultural UniversityNanchang 330045China
出 版 物:《Science China(Life Sciences)》 (中国科学(生命科学英文版))
年 卷 期:2023年第66卷第11期
页 面:2614-2628页
核心收录:
学科分类:0710[理学-生物学] 1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
基 金:supported by the National Natural Science Foundation of China(32160781)
主 题:hippocampus pig chromatin accessibility gene expression nuclei accessible chromatin regions development
摘 要:The hippocampus is a brain region associated with memory,learning and spatial navigation,its aging-related dysfunction is a common sign of Alzheimer’s *** is a good model for human neurodegenerative disease,but our understanding of the regulatory program of the pig hippocampus and its cross-species conservation in humans remains ***,we profiled chromatin accessibility in 33,409 high-quality nuclei and gene expression in 8,122 high-quality nuclei of the pig hippocampus at four postnatal *** identified 510,908 accessible chromatin regions(ACRs)in 12 major cell types,among which progenitor cells such as neuroblasts and oligodendrocyte progenitor cells showed a dynamic decrease from early to later developmental *** revealed significant enrichment of transposable elements in cell type-specific ACRs,particularly in *** identified oligodendrocytes as the most prominent cell type with the greatest number of genes that showed significant changes during the *** identified ACRs and key transcription factors underlying the trajectory of neurogenesis(such as POU3F3 and EGR1)and oligodendrocyte differentiation(RXRA and FOXO6).We examined 27 Alzheimer’s disease-related genes in our data and found that 15 showed cell type-specific activity(TREM2,RIN3 and CLU),and 15 genes displayed age-associated dynamic activity(BIN1,RABEP1 and APOE).We intersected our data with human genome-wide association study results to detect neurological disease-associated cell *** present study provides a single nucleusaccessible chromatin landscape of the pig hippocampus at different developmental stages and is helpful for the exploration of pigs as a biomedical model in human neurodegenerative diseases.