Single Cell/Nucleus Transcriptomics Comparison in Zebrafish and Humans Reveals Common and Distinct Molecular Responses to Alzheimer's Disease
- PMID: 35681503
- PMCID: PMC9180693
- DOI: 10.3390/cells11111807
Single Cell/Nucleus Transcriptomics Comparison in Zebrafish and Humans Reveals Common and Distinct Molecular Responses to Alzheimer's Disease
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.
Keywords: Alzheimer’s disease; adult brain; astroglia; fetal brain; human; microglia; neuroregeneration; single cell RNA sequencing; single nuclear RNA sequencing; telencephalon; zebrafish.
Conflict of interest statement
C.K. has an executive function in Neuron-D GmbH, which had no financial relationship to or influence on this study.
Figures







Similar articles
-
Deciphering cellular transcriptional alterations in Alzheimer's disease brains.Mol Neurodegener. 2020 Jul 13;15(1):38. doi: 10.1186/s13024-020-00392-6. Mol Neurodegener. 2020. PMID: 32660529 Free PMC article.
-
Cell type-specific potential pathogenic genes and functional pathways in Alzheimer's Disease.BMC Neurol. 2021 Oct 2;21(1):381. doi: 10.1186/s12883-021-02407-1. BMC Neurol. 2021. PMID: 34600516 Free PMC article.
-
Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity.Cell Rep. 2019 Apr 23;27(4):1307-1318.e3. doi: 10.1016/j.celrep.2019.03.090. Cell Rep. 2019. PMID: 31018142
-
Revealing cell vulnerability in Alzheimer's disease by single-cell transcriptomics.Semin Cell Dev Biol. 2023 Apr;139:73-83. doi: 10.1016/j.semcdb.2022.05.007. Epub 2022 May 24. Semin Cell Dev Biol. 2023. PMID: 35623983 Review.
-
The role of astroglia in Alzheimer's disease: pathophysiology and clinical implications.Lancet Neurol. 2019 Apr;18(4):406-414. doi: 10.1016/S1474-4422(18)30490-3. Epub 2019 Feb 19. Lancet Neurol. 2019. PMID: 30795987 Review.
Cited by
-
Local genetic covariance analysis with lipid traits identifies novel loci for early-onset Alzheimer's Disease.PLoS Genet. 2025 Mar 17;21(3):e1011631. doi: 10.1371/journal.pgen.1011631. eCollection 2025 Mar. PLoS Genet. 2025. PMID: 40096060 Free PMC article.
-
Zebrafish: A Model Deciphering the Impact of Flavonoids on Neurodegenerative Disorders.Cells. 2023 Jan 7;12(2):252. doi: 10.3390/cells12020252. Cells. 2023. PMID: 36672187 Free PMC article. Review.
-
Molecular organization of neuronal cell types and neuromodulatory systems in the zebrafish telencephalon.Curr Biol. 2024 Jan 22;34(2):298-312.e4. doi: 10.1016/j.cub.2023.12.003. Epub 2023 Dec 28. Curr Biol. 2024. PMID: 38157860 Free PMC article.
-
Universal method for the isolation of microvessels from frozen brain tissue: A proof-of-concept multiomic investigation of the neurovasculature.Brain Behav Immun Health. 2023 Sep 21;34:100684. doi: 10.1016/j.bbih.2023.100684. eCollection 2023 Dec. Brain Behav Immun Health. 2023. PMID: 37822873 Free PMC article.
-
RNA methyltransferase NSun2 deficiency promotes neurodegeneration through epitranscriptomic regulation of tau phosphorylation.Acta Neuropathol. 2023 Jan;145(1):29-48. doi: 10.1007/s00401-022-02511-7. Epub 2022 Nov 10. Acta Neuropathol. 2023. PMID: 36357715 Free PMC article.
References
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases