Protein & cell, 2021-09, Vol.12 (9), p.695-716
2021
Details
- Autor(en) / Beteiligte
- Titel
- Single-nucleus transcriptomic landscape of primate hippocampal aging
- Ist Teil von
- Protein & cell, 2021-09, Vol.12 (9), p.695-716
- Ort / Verlag
- Beijing: Higher Education Press
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- EZB Free E-Journals
- Beschreibungen/Notizen
- The hippocampus plays a crucial role in learning and memory, and its progressive deteriorationwith age is functionally linked to a variety ofhuman 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 unction along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the agedmicroglia 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1674-800XeISSN: 1674-8018DOI: 10.1007/s13238-021-00852-9Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8403220
- Format
- –
- Schlagworte
- Aging, Aging - genetics, Amyloid beta-Peptides - genetics, Amyloid beta-Peptides - metabolism, Animals, Biochemistry, Biomedical and Life Sciences, Cell Biology, Developmental Biology, DNA Damage, Endothelial cells, Endothelial Cells - cytology, Endothelial Cells - metabolism, Female, Gene expression, Gene Expression Profiling, Gene Expression Regulation, Developmental, Heterochromatin, Heterochromatin - chemistry, Heterochromatin - metabolism, High-Throughput Nucleotide Sequencing, Hippocampus, Hippocampus - cytology, Hippocampus - growth & development, Hippocampus - metabolism, Human Genetics, Humans, Inflammation, Life Sciences, Long Interspersed Nucleotide Elements, Macaca mulatta - genetics, Macaca mulatta - growth & development, Macaca mulatta - metabolism, Male, Microenvironments, Microglia, Microglia - cytology, Microglia - metabolism, Nerve Tissue Proteins - classification, Nerve Tissue Proteins - genetics, Nerve Tissue Proteins - metabolism, Neural stem cells, Neural Stem Cells - cytology, Neural Stem Cells - metabolism, Neurodegenerative diseases, Neurogenesis, Neurogenesis - genetics, Neurons - cytology, Neurons - metabolism, Oligodendroglia - cytology, Oligodendroglia - metabolism, primate, Progenitor cells, Protein Science, Research Article, Single-Cell Analysis, single-cell RNA sequencing, Stem Cells, Therapeutic applications, Transcriptome