Researchers Reveal Lineage Logics of Retinal Neurogenesis and Reprogramming
A recent study published in Journal of Cell Biology systematically analyzed the lineage progression in zebrafish retina and provided a proof-of-concept method to get specific neuron types through lineage-dependent reprogramming. This work was conducted by 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, State Key Laboratory of Neuroscience.
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 authors 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). Molecular characteristics of lineage-specific retinal progenitor cells (RPCs) were then defined using single-cell RNA sequencing. 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. This finding 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).
This work entitled “Different Lineage Contexts Direct Common Pro-neural Factors to Specify Distinct Retinal Cell Subtype” was published online in Journal of Cell Biology on July 23, 2020 . The work was carried out by graduate students WANG Mei, DU Lei and postdoctoral fellow Aih Cheun Lee under the supervision of Dr. HE Jie, the head of laboratory of Stem Cell and Neurogenesis, with help from graduate students LI Yan and QIN Huiwen. We would like to thank ZHANG Min, ZHOU Zhenning and WU Haiyan from the Molecular and Cellular Biology Core Facility at ION for their contribution to scRNA-seq and sc-ATAC. This work was supported by Chinese Academy of Sciences, Shanghai Municipal Government and National Natural Science Foundation of China.
Figure legends: (A) Schematics of zebrafish retina structure. (B) The six major neurogenic lineages in zebrafish retina. (C) OC1+ or vsx1+ RPCs generated distinct lineages. (D) Specific neuronal induction through overexpressing single pro-neural transcription factors (TFs) in OC1+ or vsx1+ RPCs. Scale bar: 10 μm. (Image by CEBSIT)
Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences, Shanghai, China.