Fig. 6

Fig. 6 Mitotic progenitors progress more slowly through the cell cycle and exit it at a reduced rate in absence of retinal input.

a–l Trajectory inference analysis performed on a cluster of mitotic progenitors. a UMAP embedding of cells color-coded by in-subset cluster identity. All subsequent panels use the same UMAP embedding. b Pseudotime analysis shows temporal progression (transition) between neighboring clusters. c, d Cells are color-coded according to their cell-cycle score. c Score of cell-cycle S-phase genes. d Score of cell-cycle G2M-phase genes. G2M high-scoring cells show a putative transition point from mitotic to postmitotic progenitors. RNA velocity analysis performed on WT (e) and lakritz (f) cells independently. RNA velocity show a similar temporal progression across groups. Velocity length inferred from RNA velocity shown for WT (g) and lakritz (h, i) cells. Color scale is the same for both groups in (g, h). i Color-scale adjusted to 5th and 95th percentile of values in the lakritz dataset. Lower velocity length shows that transition speed in lakritz is reduced overall in mitotic progenitors. In (i) higher-scoring cells show a putative bias towards G1 arrest over cell-cycle exit in the lakritz dataset. P-value calculated by comparing velocity length between WT and lakritz using the Wilcoxon signed-rank test. j, k Simplified models for mitotic progenitors across groups. In lakritz, mitotic progenitors show a bias towards G1 arrest over cell-cycle exit (dark orange arrow). Dashed arrow shows a putative transition from G1 arrest to active cycling. l A scatter plot showing the distribution of cell-cycle scores for each cell in the WT (red) and lakritz (blue) datasets. P values were calculated by comparing scores distribution between groups for each axis using the Wilcoxon signed-rank test. In lakritz, a significantly larger proportion of cells show low and negative scores on both axes, suggesting an increase in G1 cells. (Right) Bar plot summarizing the cell-cycle assignment for each cell shows a significant increase in the proportion of G1 cells in the lakritz dataset (p = 0.0376, two-sided Wilcoxon signed-rank test; n = 1333 cells, collected over 11 independent experiments. Data bars are mean ± SD).