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