Lineage tracing reveals photoreceptor precursor cell subpopulations that contribute to murine retinogenesis.

INTRODUCTION

Cell-based therapies hold great promise for treating late-stage retinal degenerative diseases. However, photoreceptor cell transplantation has been limited by poor cellular integration, suggesting that an ideal population of donor cells has not yet been defined.

METHODS

Here, we utilized single-cell RNA-sequencing and lineage tracing to assess the heterogeneity of photoreceptor precursor cells during murine retinal development.

RESULTS

Subgroup analysis revealed three transcriptionally distinct populations of Crx + cells from postnatal day 2-6 retinas which are consistent with early (Dll1+), intermediate (Neurod4+), and late (Prom1+) photoreceptor precursor cells. Lineage tracing with subpopulation-enriched Cre mice showed that Dll1+, Neurod4+, and Prom1+ cells all generate photoreceptor cells, and captured dynamic changes in gene expression suggestive of sequential states of photoreceptor differentiation. Transcriptomic analysis revealed that similar CRX + subpopulations are present in maturing human retinal organoids.

CONCLUSION

These findings highlight the heterogeneity of neonatal photoreceptor precursor cells, and could help inform future strategies to isolate an optimal population of cells for retinal regeneration.