Developmental dynamics of the single nucleus regulatory landscape of pig hippocampus  

作　　者：Siyu Yang Dong Chen Lei Xie Xiaoxiao Zou Yanyuan Xiao Lin Rao Tianxiong Yao Qing Zhang Liping Cai Fei Huang Bin Yang Lusheng Huang 

机构地区：[1]State Key Laboratory of Pig Genetic Improvement and Production Technology,Jiangxi Agricultural University,Nanchang 330045,China

出　　处：《Science China(Life Sciences)》2023年第11期2614-2628,共15页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(32160781).

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 disease.Pig 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 limited.Here,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 stages.We 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 stages.We revealed significant enrichment of transposable elements in cell type-specific ACRs,particularly in neuroblasts.We identified oligodendrocytes as the most prominent cell type with the greatest number of genes that showed significant changes during the development.We 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 types.The 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.

关 键 词：HIPPOCAMPUS PIG chromatin accessibility gene expression NUCLEI accessible chromatin regions development 

分 类 号：R741[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]