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Cell Rep. 2019 Apr 23;27(4):1307-1318.e3. doi: 10.1016/j.celrep.2019.03.090.

Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity.

Author information

1
Kizil Lab, German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany. Electronic address: mehmet.cosacak@dzne.de.
2
Kizil Lab, German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany.
3
DRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden, Fetscherstr. 105, 01307 Dresden, Germany.
4
B CUBE, Center for Molecular Bioengineering, TU Dresden, Tatzberg 41, 10307 Dresden, Germany.
5
Kizil Lab, German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany; Kizil Lab, Technische Universität Dresden, Center for Regenerative Therapies Dresden (CRTD), Fetscherstr. 105, 01307 Dresden, Germany. Electronic address: caghan.kizil@dzne.de.

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.

KEYWORDS:

Alzheimer’s disease; Fgf signaling; amyloid-beta42; interaction map; interleukin-4; neural stem cell; neuron; plasticity; single cell sequencing; zebrafish

PMID:
31018142
DOI:
10.1016/j.celrep.2019.03.090
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