ZFIN ID: ZDB-PUB-190425-21
Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity
Cosacak, M.I., Bhattarai, P., Reinhardt, S., Petzold, A., Dahl, A., Zhang, Y., Kizil, C.
Date: 2019
Source: Cell Reports   27: 1307-1318.e3 (Journal)
Registered Authors: Bhattarai, Prabesh, Cosacak, Mehmet Ilyas, Kizil, Caghan
Keywords: Alzheimer’s disease, Fgf signaling, amyloid-beta42, interaction map, interleukin-4, neural stem cell, neuron, plasticity, single cell sequencing, zebrafish
Microarrays: GEO:GSE118577
MeSH Terms:
  • Alzheimer Disease/etiology
  • Alzheimer Disease/genetics
  • Alzheimer Disease/pathology*
  • Amyloid beta-Peptides/toxicity*
  • Animals
  • Animals, Genetically Modified
  • Brain/drug effects
  • Brain/metabolism
  • Brain/pathology*
  • Gene Regulatory Networks
  • Interleukin-4/toxicity
  • Neural Stem Cells/drug effects
  • Neural Stem Cells/metabolism
  • Neural Stem Cells/pathology*
  • Neuronal Plasticity/drug effects
  • Neuronal Plasticity/genetics*
  • Single-Cell Analysis/methods*
  • Transcriptome/drug effects*
  • Zebrafish
PubMed: 31018142 Full text @ Cell Rep.
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ABSTRACT
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.
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