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ZFIN ID: ZDB-PUB-200724-21
Different lineage contexts direct common pro-neural factors to specify distinct retinal cell subtypes
Wang, M., Du, L., Lee, A.C., Li, Y., Qin, H., He, J.
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
Microarrays: 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.
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.