Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity
| Autor: | Andreas Dahl, Prabesh Bhattarai, Andreas Petzold, Susanne Reinhardt, Caghan Kizil, Mehmet Ilyas Cosacak, Yixin Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Amyloid drug effects [Neural Stem Cells] etiology [Alzheimer Disease] Endogeny genetics [Alzheimer Disease] metabolism [Neural Stem Cells] pathology [Neural Stem Cells] genetics [Neuronal Plasticity] General Biochemistry Genetics and Molecular Biology Transcriptome Animals Genetically Modified 03 medical and health sciences pathology [Alzheimer Disease] 0302 clinical medicine Neural Stem Cells Alzheimer Disease pathology [Brain] drug effects [Neuronal Plasticity] medicine Animals Gene Regulatory Networks ddc:610 Zebrafish methods [Single-Cell Analysis] Amyloid beta-Peptides Neuronal Plasticity biology Brain biology.organism_classification Neural stem cell toxicity [Amyloid beta-Peptides] 030104 developmental biology medicine.anatomical_structure nervous system Single cell sequencing drug effects [Transcriptome] metabolism [Brain] toxicity [Interleukin-4] drug effects [Brain] Interleukin-4 Neuron Single-Cell Analysis Stem cell Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cell reports 27(4), 1307-1318.e3 (2019). doi:10.1016/j.celrep.2019.03.090 |
| DOI: | 10.1016/j.celrep.2019.03.090 |
| Popis: | The neural stem cell (NSC) reservoir can be harnessed for stem cell-based regenerative therapies. Zebrafish remarkably regenerate their brain by inducing NSC plasticity in a Amyloid-β-42 (Aβ42)-induced experimental Alzheimer's disease (AD) model. Interleukin-4 (IL-4) is also critical for AD-induced NSC proliferation. However, the mechanisms of this response have remained unknown. Using single-cell transcriptomics in the adult zebrafish brain, we identify distinct subtypes of NSCs and neurons and differentially regulated pathways and their gene ontologies and investigate how cell-cell communication is altered through ligand-receptor pairs in AD conditions. Our results propose the existence of heterogeneous and spatially organized stem cell populations that react distinctly to amyloid toxicity. This resource article provides an extensive database for the molecular basis of NSC plasticity in the AD model of the adult zebrafish brain. Further analyses of stem cell heterogeneity and neuro-regenerative ability at single-cell resolution could yield drug targets for mobilizing NSCs for endogenous neuro-regeneration in humans. |
| Databáze: | OpenAIRE |
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