PMID- 34052996 OWN - NLM STAT- MEDLINE VI - 12 IP - 9 TI - Single-nucleus transcriptomic landscape of primate hippocampal aging. PG - 695-716 CI - © 2021. The Author(s). LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Protein Cell JT - Protein & cell JID - 101532368 IS - 1674-8018 (Electronic) LID - 10.1007/s13238-021-00852-9 [doi] FAU - Zhang, Hui AU - Zhang H AD - State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. FAU - Li, Jiaming AU - Li J AD - CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. AD - China National Center for Bioinformation, Beijing, 100101, China. AD - Sino-Danish College, University of Chinese Academy of Sciences, Beijing, 101408, China. AD - Sino-Danish Center for Education and Research, Beijing, 101408, China. FAU - Ren, Jie AU - Ren J AUID- ORCID: 0000-0002-6450-3163 AD - CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. AD - China National Center for Bioinformation, Beijing, 100101, China. AD - Sino-Danish College, University of Chinese Academy of Sciences, Beijing, 101408, China. FAU - Sun, Shuhui AU - Sun S AD - State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. AD - Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. FAU - Ma, Shuai AU - Ma S AD - State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. AD - Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. FAU - Zhang, Weiqi AU - Zhang W AUID- ORCID: 0000-0002-8885-5104 AD - CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. AD - China National Center for Bioinformation, Beijing, 100101, China. AD - Sino-Danish College, University of Chinese Academy of Sciences, Beijing, 101408, China. FAU - Yu, Yang AU - Yu Y AD - Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, 100191, China. AD - Stem Cell Research Center, Peking University Third Hospital, Beijing, 100191, China. FAU - Cai, Yusheng AU - Cai Y AD - State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. AD - Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. FAU - Yan, Kaowen AU - Yan K AD - State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. AD - Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. FAU - Li, Wei AU - Li W AD - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. AD - Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. FAU - Hu, Baoyang AU - Hu B AD - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. AD - Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. FAU - Chan, Piu AU - Chan P AD - Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China. FAU - Zhao, Guo-Guang AU - Zhao GG AD - Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China. AD - Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. FAU - Belmonte, Juan Carlos Izpisua AU - Belmonte JCI AD - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA. FAU - Zhou, Qi AU - Zhou Q AD - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. AD - Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. FAU - Qu, Jing AU - Qu J AUID- ORCID: 0000-0002-3988-5067 AD - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. qujing@ioz.ac.cn. AD - Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. qujing@ioz.ac.cn. FAU - Wang, Si AU - Wang S AUID- ORCID: 0000-0003-2431-0612 AD - Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China. wangsi@xwh.ccmu.edu.cn. AD - Aging Translational Medicine Center, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. wangsi@xwh.ccmu.edu.cn. FAU - Liu, Guang-Hui AU - Liu GH AUID- ORCID: 0000-0001-9289-8177 AD - State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ioz.ac.cn. AD - Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China. ghliu@ioz.ac.cn. AD - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ioz.ac.cn. AD - University of Chinese Academy of Sciences, Beijing, 100049, China. ghliu@ioz.ac.cn. AD - Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. ghliu@ioz.ac.cn. IS - 1674-800X (Linking) RN - 0 (Amyloid beta-Peptides) RN - 0 (Heterochromatin) RN - 0 (Nerve Tissue Proteins) SB - IM MH - Aging/*genetics MH - Amyloid beta-Peptides/genetics/metabolism MH - Animals MH - DNA Damage MH - Endothelial Cells/cytology/metabolism MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation, Developmental MH - Heterochromatin/chemistry/metabolism MH - High-Throughput Nucleotide Sequencing MH - Hippocampus/cytology/growth & development/*metabolism MH - Humans MH - Inflammation MH - Long Interspersed Nucleotide Elements MH - Macaca mulatta/*genetics/growth & development/metabolism MH - Male MH - Microglia/cytology/metabolism MH - Nerve Tissue Proteins/classification/*genetics/metabolism MH - Neural Stem Cells/cytology/metabolism MH - Neurogenesis/*genetics MH - Neurons/cytology/metabolism MH - Oligodendroglia/cytology/metabolism MH - Single-Cell Analysis MH - *Transcriptome OTO - NOTNLM OT - aging OT - hippocampus OT - primate OT - single-cell RNA sequencing PMC - PMC8403220 DCOM- 20220126 LR - 20230920 DP - 202109 DEP - 20210530 AB - 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.