Deciphering molecular heterogeneity and dynamics of human hippocampal neural stem cells at different ages and injury states

Junjun Yao; Shaoxing Dai; Ran Zhu; Ju Tan; Qiancheng Zhao; Yu Yin; Jiansen Sun; Xuewei Du; Longjiao Ge; Jianhua Xu; Chunli Hou; Nan Li; Jun Li; Weizhi Ji; Chuhong Zhu; Runrui Zhang; Tianqing Li

doi:10.7554/eLife.89507

eLife (Apr 2024)

Deciphering molecular heterogeneity and dynamics of human hippocampal neural stem cells at different ages and injury states

Junjun Yao,
Shaoxing Dai,
Ran Zhu,
Ju Tan,
Qiancheng Zhao,
Yu Yin,
Jiansen Sun,
Xuewei Du,
Longjiao Ge,
Jianhua Xu,
Chunli Hou,
Nan Li,
Jun Li,
Weizhi Ji,
Chuhong Zhu,
Runrui Zhang,
Tianqing Li

Affiliations

Junjun Yao: ORCiD; State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Shaoxing Dai: State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Ran Zhu: ORCiD; State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Ju Tan: Department of Anatomy, National and Regional Engineering Laboratory of Tissue Engineering, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing, China
Qiancheng Zhao: State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Yu Yin: State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Jiansen Sun: Zhong-Zhi- Yi-Gu Research Institute, Chongqing, China
Xuewei Du: State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Longjiao Ge: State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Jianhua Xu: Department of Anatomy, National and Regional Engineering Laboratory of Tissue Engineering, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing, China
Chunli Hou: Department of Anatomy, National and Regional Engineering Laboratory of Tissue Engineering, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing, China
Nan Li: ORCiD; State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Jun Li: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Weizhi Ji: State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Chuhong Zhu: Department of Anatomy, National and Regional Engineering Laboratory of Tissue Engineering, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing, China
Runrui Zhang: ORCiD; State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China
Tianqing Li: ORCiD; State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China

DOI: https://doi.org/10.7554/eLife.89507
Journal volume & issue: Vol. 12

Abstract

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While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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