| Title | Single-nucleus transcriptomic landscape of primate hippocampal aging |
| Authors | Zhang, Hui Li, Jiaming Ren, Jie Sun, Shuhui Ma, Shuai Zhang, Weiqi Yu, Yang Cai, Yusheng Yan, Kaowen Li, Wei Hu, Baoyang Chan, Piu Zhao, Guo-Guang Belmonte, Juan Carlos Izpisua Zhou, Qi Qu, Jing Wang, Si Liu, Guang-Hui |
| Affiliation | Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing 100101, Peoples R China Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Natl Clin Res Ctr Geriatr Disorders, Xuanwu Hosp, Beijing 100053, Peoples R China Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genom & Precis Med, Beijing 100101, Peoples R China Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China Univ Chinese Acad Sci, Beijing 100049, Peoples R China China Natl Ctr Bioinformat, Beijing 100101, Peoples R China Capital Med Univ, Xuanwu Hosp, Aging Translat Med Ctr, Beijing 100053, Peoples R China Capital Med Univ, Xuanwu Hosp, Dept Neurosurg, Beijing 100053, Peoples R China Univ Chinese Acad Sci, Sino Danish Coll, Beijing 101408, Peoples R China Sino Danish Ctr Educ & Res, Beijing 101408, Peoples R China Peking Univ Third Hosp, Dept Obstet & Gynecol, Ctr Reprod Med, Beijing 100191, Peoples R China Beijing Inst Stem Cell & Regenerat Med, Beijing 100101, Peoples R China Peking Univ Third Hosp, Stem Cell Res Ctr, Beijing 100191, Peoples R China Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA |
| Keywords | NEURAL STEM-CELLS AMYLOID-BETA ADULT NEUROGENESIS ALZHEIMERS-DISEASE NONHUMAN-PRIMATES SENESCENT CELLS RNA-SEQ EXPRESSION AGE DYNAMICS |
| Issue Date | May-2021 |
| Publisher | PROTEIN & CELL |
| Abstract | The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases. |
| URI | http://hdl.handle.net/20.500.11897/622625 |
| ISSN | 1674-800X |
| DOI | 10.1007/s13238-021-00852-9 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 |
