Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity.
Alzheimer Disease
/ etiology
Amyloid beta-Peptides
/ toxicity
Animals
Animals, Genetically Modified
Brain
/ drug effects
Gene Regulatory Networks
Interleukin-4
/ toxicity
Neural Stem Cells
/ drug effects
Neuronal Plasticity
/ drug effects
Single-Cell Analysis
/ methods
Transcriptome
/ drug effects
Zebrafish
Alzheimer’s disease
Fgf signaling
amyloid-beta42
interaction map
interleukin-4
neural stem cell
neuron
plasticity
single cell sequencing
zebrafish
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
23 04 2019
23 04 2019
Historique:
received:
08
10
2018
revised:
21
02
2019
accepted:
25
03
2019
entrez:
25
4
2019
pubmed:
25
4
2019
medline:
18
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31018142
pii: S2211-1247(19)30429-2
doi: 10.1016/j.celrep.2019.03.090
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Interleukin-4
207137-56-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1307-1318.e3Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.