Whether adult hippocampal neurogenesis(AHN)persists in adult and aged humans continues to be extensively debated.A major question is whether the markers identified in rodents are reliable enough to reveal new neurons and the neurogenic trajectory in primates.Here,to provide a better understanding of AHN in primates and to reveal more novel markers for distinct cell types,droplet-based single-nucleus RNA sequencing(snRNA-seq)is used to investigate the cellular heterogeneity and molecular characteristics of the hippocampi in macaques across the lifespan and in aged humans.All of the major cell types in the hippocampus and their expression profiles were identified.The dynamics of the neurogenic lineage was revealed and the diversity of astrocytes and microglia was delineated.In the neurogenic lineage,the regulatory continuum from adult neural stem cells(NSCs)to immature and mature granule cells was investigated.A group of primate-specific markers were identified.We validated ETNPPL as a primate-specific NSC marker and verified STMN1 and STMN2 as immature neuron markers in primates.Furthermore,we illustrate a cluster of active astrocytes and microglia exhibiting proinflammatory responses in aged samples.The interaction analysis and the comparative investigation on published datasets and ours imply that astrocytes provide signals inducing the proliferation,quiescence and inflammation of adult NSCs at different stages and that the proinflammatory status of astrocytes probably contributes to the decrease and variability of AHN in adults and elderly individuals.

Wei Wang;Mengdi Wang;Meng Yang;Bo Zeng;Wenying Qiu;Qiang Ma;Xiaoxi Jing;Qianqian Zhang;Bosong Wang;Chonghai Yin;Jiyao Zhang;Yuxin Ge;Yufeng Lu;Weizhi Ji;Qian Wu;Chao Ma;Xiaoqun Wang

State Key Laboratory of Cognitive Neuroscience and Learning,IDG/McGovern Institute for Brain Research,Beijing Normal University,Beijing,China;State Key Laboratory of Brain and Cognitive Science,CAS Center for Excellence in Brain Science and Intelligence Technology(Shanghai),Institute of Biophysics,Chinese Academy of Sciences,Beijing,China;Changping Laboratory,Beijing,China;University of Chinese Academy of Sciences,Beijing,China;Institute of Basic Medical Sciences,Neuroscience Center,National Human Brain Bank for Development and Function,Chinese Academy of Medical Sciences;Department of Human Anatomy,Histology and Embryology,School of Basic Medicine,Peking Union Medical College,Beijing,China;Yunnan Key Laboratory of Primate Biomedical Research,Institute of Primate Translational Medicine,Kunming University of Science and Technology,Kunming,Yunan,China;Advanced Innovation Center for Human Brain Protection,Beijing Institute for Brain Disorders,Capital Medical University,Beijing,China

细胞研究（英文版）

[1]Wei Wang;Mengdi Wang;Meng Yang;Bo Zeng;Wenying Qiu;Qiang Ma;Xiaoxi Jing;Qianqian Zhang;Bosong Wang;Chonghai Yin;Jiyao Zhang;Yuxin Ge;Yufeng Lu;Weizhi Ji;Qian Wu;Chao Ma;Xiaoqun Wang-.Transcriptome dynamics of hippocampal neurogenesis in macaques across the lifespan and aged humans)[J].细胞研究（英文版）,2022(08):729-743

hippocampi,ETNPPL,STMN2

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