In a study published online in Journal of Cell Biology on July 23, the researchers from Dr. HE Jie’s Lab at the Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences systematically analyzed the lineage progression in zebrafish retina and provided a proof-of-concept method to get specific neuron types through lineage-dependent reprogramming.

Neurons are derived from stereotyped lineages in invertebrate species like C. elegans and Drosophila. However, it has been controversial for about 30 years whether neurogenesis is lineage-dependent in vertebrate species.

Taking advantage of transparency in early zebrafish embryo, the researchers analyzed about 1000 cell lineages in zebrafish retina in vivo and revealed the six major neurogenic lineages, which were responsible for all the five neuron types in retina (retina ganglion cell, amacrine cell, bipolar cell, horizontal cell and photoreceptor cell).

Using single-cell RNA sequencing, they then defined molecular characteristics of lineage-specific retinal progenitor cells (RPCs). These results showed evidence in vertebrates that neurogenesis was mostly dependent on cell lineage.   

Interestingly, RPCs could be efficiently reprogrammed into specific neuron types through overexpression of a single transcription factor in vivo, and the reprogramming result was lineage-dependent.

The findings in this study proved that lineage-dependent reprogramming might be a useful way to regenerate specific neuron for disease treatment, such as glaucoma (a loss of retina ganglion cells) and macular degeneration (a loss of photoreceptor cells).