Molecular landscapes of human hippocampal immature neurons across lifespan
| Autor: | Yi Zhou, Yijing Su, Shiying Li, Benjamin C. Kennedy, Daniel Y. Zhang, Allison M. Bond, Yusha Sun, Fadi Jacob, Lu Lu, Peng Hu, Angela N. Viaene, Ingo Helbig, Sudha K. Kessler, Timothy Lucas, Ryan D. Salinas, Xiaosong Gu, H. Isaac Chen, Hao Wu, Joel E. Kleinman, Thomas M. Hyde, David W. Nauen, Daniel R. Weinberger, Guo-li Ming, Hongjun Song |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Neurons Aging Multidisciplinary Transcription Genetic Sequence Analysis RNA Gene Expression Profiling Neurogenesis Longevity Reproducibility of Results Hippocampus Article Machine Learning Mice Neural Stem Cells Alzheimer Disease Dentate Gyrus Animals Humans Single-Cell Analysis Cell Proliferation |
| Zdroj: | Nature |
| ISSN: | 1476-4687 |
| Popis: | Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents(1,2) and they are dysregulated in multiple human neurological disorders(3–5). Little is known about molecular characteristics of adult human hippocampal imGCs and even their existence is under debate(1,6–8). Here we performed single-nucleus RNA-sequencing (snRNA-seq) aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus during infant, child, adolescent, adult, and aging stages. We identified common molecular hallmarks of human imGCs across the lifespan and discovered age-dependent transcriptional dynamics unique to human imGCs that suggest changes in cellular functionality, niche interactions, and disease relevance, in contrast to those in mice9. We also found a decreased number of imGCs with altered gene expression in Alzheimer’s disease (AD). Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a significant number of imGCs in the adult human hippocampus via low frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in AD. |
| Databáze: | OpenAIRE |
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