PUBLICATION
Single Cell/Nucleus Transcriptomics Comparison in Zebrafish and Humans Reveals Common and Distinct Molecular Responses to Alzheimer's Disease
- Authors
- Cosacak, M.I., Bhattarai, P., De Jager, P.L., Menon, V., Tosto, G., Kizil, C.
- ID
- ZDB-PUB-220611-2
- Date
- 2022
- Source
- Cells 11(11): (Journal)
- Registered Authors
- Bhattarai, Prabesh, Cosacak, Mehmet Ilyas, Kizil, Caghan
- Keywords
- Alzheimer’s disease, adult brain, astroglia, fetal brain, human, microglia, neuroregeneration, single cell RNA sequencing, single nuclear RNA sequencing, telencephalon, zebrafish
- Datasets
- GEO:GSE118577, GEO:GSE161834, GEO:GSE124162, GEO:GSE186874
- MeSH Terms
-
- Alzheimer Disease*/genetics
- Animals
- Humans
- Neurogenesis/genetics
- Solitary Nucleus
- Transcriptome/genetics
- Zebrafish/genetics
- PubMed
- 35681503 Full text @ Cells
Citation
Cosacak, M.I., Bhattarai, P., De Jager, P.L., Menon, V., Tosto, G., Kizil, C. (2022) Single Cell/Nucleus Transcriptomics Comparison in Zebrafish and Humans Reveals Common and Distinct Molecular Responses to Alzheimer's Disease. Cells. 11(11).
Abstract
Neurogenesis is significantly reduced in Alzheimer's disease (AD) and is a potential therapeutic target. Contrary to humans, a zebrafish can regenerate its diseased brain, and thus is ideal for studying neurogenesis. To compare the AD-related molecular pathways between humans and zebrafish, we compared single cell or nuclear transcriptomic data from a zebrafish amyloid toxicity model and its controls (N = 12) with the datasets of two human adult brains (N = 10 and N = 48 (Microglia)), and one fetal brain (N = 10). Approximately 95.4% of the human and zebrafish cells co-clustered. Within each cell type, we identified differentially expressed genes (DEGs), enriched KEGG pathways, and gene ontology terms. We studied synergistic and non-synergistic DEGs to point at either common or uniquely altered mechanisms across species. Using the top DEGs, a high concordance in gene expression changes between species was observed in neuronal clusters. On the other hand, the molecular pathways affected by AD in zebrafish astroglia differed from humans in favor of the neurogenic pathways. The integration of zebrafish and human transcriptomes shows that the zebrafish can be used as a tool to study the cellular response to amyloid proteinopathies. Uniquely altered pathways in zebrafish could highlight the specific mechanisms underlying neurogenesis, which are absent in humans, and could serve as potential candidates for therapeutic developments.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping