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Peer-reviewedCC BY 4.0Scientific Reports

Pseudotime trajectory analysis reveals divergent rod photoreceptor states during dark adaptation

Abstract

Rod photoreceptors face a high ATP demand in darkness, yet the molecular programs supporting dark adaptation remain difficult to dissect in vivo. Here, I re-analyzed publicly available murine retinal single-cell RNA-seq data and reconstructed rod-state dynamics across the light-to-dark transition using pseudotime trajectory inference. I found that dark-adapting rods diverge from a common state into two distinct lineages. Lineage 1 is characterized by elevated MYC-driven anabolic programs alongside increased reactive oxygen species (ROS) response and unfolded protein response (UPR)/ER stress signatures. In contrast, Lineage 2 exhibits an altered RNA-processing state with a markedly higher unspliced RNA fraction. Furthermore, Lineage 2 relatively preserves the STRADA/MO25β (CAB39L) module, which supports LKB1-AMPK energy sensing. Together, these findings support a model in which dark-adapting rods bifurcate into a MYC-driven anabolic state and an RNA-processing-altered state, a balance that may be biased by an LKB1–AMPK-associated mechanism. This integrative computational analysis provides a descriptive framework for rod photoreceptor adaptation, guiding future biochemical and molecular experiments to determine the molecular basis and drivers of this divergence.

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BibTeX
@article{ishii2026pseudotime,
  title = {{Pseudotime trajectory analysis reveals divergent rod photoreceptor states during dark adaptation}},
  author = {Ryutaro Ishii},
  journal = {Scientific Reports},
  year = {2026},
  month = oct,
  doi = {10.1038/s41598-026-74692-0},
  url = {https://www.nature.com/articles/s41598-026-74692-0},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Pseudotime trajectory analysis reveals divergent rod photoreceptor states during dark adaptation
AU  - Ryutaro Ishii
PY  - 2026
DA  - 2026/10/04
JO  - Scientific Reports
DO  - 10.1038/s41598-026-74692-0
UR  - https://www.nature.com/articles/s41598-026-74692-0
AB  - Rod photoreceptors face a high ATP demand in darkness, yet the molecular programs supporting dark adaptation remain difficult to dissect in vivo. Here, I re-analyzed publicly available murine retinal single-cell RNA-seq data and reconstructed rod-state dynamics across the light-to-dark transition using pseudotime trajectory inference. I found that dark-adapting rods diverge from a common state into two distinct lineages. Lineage 1 is characterized by elevated MYC-driven anabolic programs alongside increased reactive oxygen species (ROS) response and unfolded protein response (UPR)/ER stress signatures. In contrast, Lineage 2 exhibits an altered RNA-processing state with a markedly higher unspliced RNA fraction. Furthermore, Lineage 2 relatively preserves the STRADA/MO25β (CAB39L) module, which supports LKB1-AMPK energy sensing. Together, these findings support a model in which dark-adapting rods bifurcate into a MYC-driven anabolic state and an RNA-processing-altered state, a balance that may be biased by an LKB1–AMPK-associated mechanism. This integrative computational analysis provides a descriptive framework for rod photoreceptor adaptation, guiding future biochemical and molecular experiments to determine the molecular basis and drivers of this divergence.
SN  - 2045-2322
ER  -