Extended Data Fig. 8: The regeneration gene-expression profile is sustained at 21 days only with an NPC graft, and not with a non-stimulatory MSC graft, and correlates with neuronal developmental transcriptomes.

a, Number of significantly differentially expressed genes of non-regenerating (no graft and MSC graft) and regenerating (NPC graft) CST neurons relative to intact CST neurons (FDR < 0.1, Benjamini–Hochberg, two-sided) at 21 days after injury. Red, increased expression; green, reduced expression. b, Heat map of the top 1,000 significantly differentially regulated transcripts (FDR < 0.1) upon injury and upon regeneration, relative to the intact state, at 21 days after injury. Red, increased expression; green, reduced expression. The intensity of the colour reflects the degree of gene regulation compared to the intact state. Transcripts are arranged by hierarchical clustering. The non-regenerating conditions (no graft and MSC graft) show gene-expression patterns similar to one another; and, in both cases, gene expression is not sustained in comparison to the regenerating condition (NPC graft). n = 3 biological replicates. c, Differentially expressed genes (FDR < 0.1) of a previous neuronal development study (GSE2039) for different time points against P14 (log-transformed fold change) was compared to CST data against the intact condition. Numbers indicate the Pearson correlation coefficient of the two datasets. Colour indicates the magnitude of the correlation coefficient (side bar). Values in parentheses are statistical significance (P values) of the correlation coefficients. n = 2 biological replicates for day-10 non-regenerating and n = 3 biological replicates for all other conditions. d–f, Overlapping signalling pathways of regenerating versus non-regenerating CST neurons (FDR < 0.1) using Ingenuity Pathway Analysis software at 10 (d), 14 (e) and 21 (f) days after injury. The network of overlapping signalling pathways shows each pathway as a single ‘node’ that is coloured proportionally to the right-tailed Fisher’s exact test P value; darker red, more significant. Individual scaling of P values is listed at the bottom of each graph. A line connects any two pathways when there is at least one dataset molecule in common between them. Pathways of similar function are clustered together (dashed blue outlines). n = 2 biological replicates for day-10 non-regenerating and n = 3 biological replicates for all other conditions.