Fig. 4. Expression of cone and neuronal/ganglion cell markers in retinoblastoma and retinal organoids.
a Heatmap showing the expression of cone and ganglion markers in retinal organoids at different differentiation time points, and in subtype 1 and subtype 2 tumors assessed by NanoString technology. Differences in gene expression between the two subtypes were assessed by two-sided t-tests with BH correction. Exact p-values are provided in Supplementary Data 4. b Pearson’s correlation of the expression of 8 cone markers, between the centroids of the 2 retinoblastoma subtypes and retinal organoids at different time points in differentiation. C1: centroid of subtype 1; C2: centroid of subtype 2. c Phylogenetic tree based on cone marker expression, for retinal organoids at different differentiation time points and for retinoblastoma samples. d Immunohistochemical staining of CRX, ARR3, EBF3, and Ki-67 in normal retina and retinoblastoma. For RB617, the black arrows indicate the mutually exclusive patterns for ARR3 and EBF3. Immunohistochemistry experiments were performed on 34 samples (subtype 1, n = 9; subtype 2, n = 25). Two representative images are shown for each subtype. e Boxplots showing the quick score (QS) for the differentiation markers used in the immunohistochemical analysis: CRX, ARR3, and EBF3. In the boxplots, the central mark indicates the median and the bottom and top edges of the box the 25th and 75th percentiles. The whiskers are the smaller of 1.5 times the interquartile range or the length of the 25th percentiles to the smallest data point or the 75th percentiles to the largest data point. Data points outside the whiskers are outliers. Two-sided Wilcoxon tests were used.