PUBLICATION

Different lineage contexts direct common pro-neural factors to specify distinct retinal cell subtypes

Authors
Wang, M., Du, L., Lee, A.C., Li, Y., Qin, H., He, J.
ID
ZDB-PUB-200724-21
Date
2020
Source
The Journal of cell biology   219(9): (Journal)
Registered Authors
Du, Lei, He, Jie, Li, Yan, Qin, Huiwen, Wang, Mei
Keywords
none
Datasets
GEO:GSE150839
MeSH Terms
  • Amacrine Cells/physiology
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation/physiology
  • Cell Lineage/physiology*
  • Chromatin/physiology
  • Gene Expression Regulation, Developmental/physiology
  • Neurogenesis/physiology
  • Retina/physiology*
  • Retinal Neurons/physiology*
  • Zebrafish/physiology
PubMed
32699896 Full text @ J. Cell Biol.
Abstract
How astounding neuronal diversity arises from variable cell lineages in vertebrates remains mostly elusive. By in vivo lineage tracing of ∼1,000 single zebrafish retinal progenitors, we identified a repertoire of subtype-specific stereotyped neurogenic lineages. Remarkably, within these stereotyped lineages, GABAergic amacrine cells were born with photoreceptor cells, whereas glycinergic amacrine cells were born with OFF bipolar cells. More interestingly, post-mitotic differentiation blockage of GABAergic and glycinergic amacrine cells resulted in their respecification into photoreceptor and bipolar cells, respectively, suggesting lineage constraint in cell subtype specification. Using single-cell RNA-seq and ATAC-seq analyses, we further identified lineage-specific progenitors, each defined by specific transcription factors that exhibited characteristic chromatin accessibility dynamics. Finally, single pro-neural factors could specify different neuron types/subtypes in a lineage-dependent manner. Our findings reveal the importance of lineage context in defining neuronal subtypes and provide a demonstration of in vivo lineage-dependent induction of unique retinal neuron subtypes for treatment purposes.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping